Regulation of GH and GH Signaling by Nutrients

Marina Caputo, Stella Pigni, Emanuela Agosti, Tommaso Daffara, Alice Ferrero, Nicoletta Filigheddu, Flavia Prodam, Marina Caputo, Stella Pigni, Emanuela Agosti, Tommaso Daffara, Alice Ferrero, Nicoletta Filigheddu, Flavia Prodam

Abstract

Growth hormone (GH) and insulin-like growth factor-1 (IGF-I) are pleiotropic hormones with important roles in lifespan. They promote growth, anabolic actions, and body maintenance, and in conditions of energy deprivation, favor catabolic feedback mechanisms switching from carbohydrate oxidation to lipolysis, with the aim to preserve protein storages and survival. IGF-I/insulin signaling was also the first one identified in the regulation of lifespan in relation to the nutrient-sensing. Indeed, nutrients are crucial modifiers of the GH/IGF-I axis, and these hormones also regulate the complex orchestration of utilization of nutrients in cell and tissues. The aim of this review is to summarize current knowledge on the reciprocal feedback among the GH/IGF-I axis, macro and micronutrients, and dietary regimens, including caloric restriction. Expanding the depth of information on this topic could open perspectives in nutrition management, prevention, and treatment of GH/IGF-I deficiency or excess during life.

Keywords: GH; IGF-I; diet; fasting; feeding; food; mineral; nutrient; regulation; vitamin.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Regulation among the GH/IGF-I/ghrelin axis and macronutrients, fasting, and vitamin D. Created with BioRender.com. SST = somatostatin; CHO = carbohydrates; AA = amino acids; Leu = leucine; Val = valine; Trp = tryptophan; Met = methionine; Phe phenylalanine; BCAA = branched chain; FFA = free fatty acids; 1,25(OH)2D3 = calcitriol.

References

    1. Moøller N., Joørgensen J.O.L. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr. Rev. 2009;30:152–177. doi: 10.1210/er.2008-0027.
    1. Bartke A., Darcy J. GH and ageing: Pitfalls and new insights. Best Pract. Res. Clin. Endocrinol. Metab. 2017;31:113–125. doi: 10.1016/j.beem.2017.02.005.
    1. Poudel S.B., Dixit M., Neginskaya M., Nagaraj K., Pavlov E., Werner H., Yakar S. Effects of GH/IGF on the Aging Mitochondria. Cells. 2020;9:1384. doi: 10.3390/cells9061384.
    1. Donohoe C.L., Lysaght J., O’Sullivan J., Reynolds J.V. Emerging Concepts Linking Obesity with the Hallmarks of Cancer. Trends Endocrinol. Metab. 2017;28:46–62. doi: 10.1016/j.tem.2016.08.004.
    1. López-Otín C., Kroemer G. Hallmarks of Health. Cell. 2021;184:33–63. doi: 10.1016/j.cell.2020.11.034.
    1. Chen E.Y., Liao Y.C., Smith D.H., Barrera-Saldaña H.A., Gelinas R.E., Seeburg P.H. The human growth hormone locus: Nucleotide sequence, biology, and evolution. Genomics. 1989;4:479–497. doi: 10.1016/0888-7543(89)90271-1.
    1. Baumann G.P. Growth hormone isoforms. Growth Horm. IGF Res. 2009;19:333–340. doi: 10.1016/j.ghir.2009.04.011.
    1. Ho K.Y., Veldhuis J.D., Johnson M.L., Furlanetto R., Evans W.S., Alberti K.G.M.M., Thorner M.O. Fasting enhances growth hormone secretion and amplifies the complex rhythms of growth hormone secretion in man. J. Clin. Investig. 1988;81:968–975. doi: 10.1172/JCI113450.
    1. Hartman M.L., Veldhuis J.D., Thorner M.O. Normal control of growth hormone secretion. Horm. Res. 1993;40:37–47. doi: 10.1159/000183766.
    1. Bonert V., Melmed S. The Pituitary. 4th ed. Academic Press; Cambridge, MA, USA: 2017.
    1. Giustina A., Veldhuis J.D. Pathophysiology of the Neuroregulation of Growth Hormone Secretion in Experimental Animals and the Human. Endocr. Rev. 1998;19:717–797. doi: 10.1210/er.19.6.717.
    1. Eigler T., Ben-Shlomo A. Somatostatin system: Molecular mechanisms regulating anterior pituitary hormones. J. Mol. Endocrinol. 2014;53 doi: 10.1530/JME-14-0034.
    1. Ghigo E., Arvat E., Bellone J., Ramunni J., Camanni F. Neurotransmitter Control of Growth Hormone Secretion in Humans. J. Pediatr. Endocrinol. Metab. 1993;6:263–266. doi: 10.1515/JPEM.1993.6.3-4.263.
    1. Vance M.L., Hartman M.L., Thorner M.O. Growth hormone and nutrition. Horm. Res. Paediatr. 1992;38:85–88. doi: 10.1159/000182577.
    1. Hartman M.L., Clayton P.E., Johnson M.L., Celniker A., Perlman A.J., Alberti K.G.M.M., Thorner M.O. A low dose euglycemic infusion of recombinant human insulin-like growth factor I rapidly suppresses fasting-enhanced pulsatile growth hormone secretion in humans. J. Clin. Investig. 1993;91:2453–2462. doi: 10.1172/JCI116480.
    1. Vottero A., Guzzetti C., Loche S. Hormone Resistance and Hypersensitivity: From Genetics to Clinical Management. Volume 24. S. Karger; Basel, Switzerland: 2013. New aspects of the physiology of the GH-IGF-1 axis; pp. 96–105.
    1. Mertani H.C., Delehaye-Zervas M.C., Martini J.F., Postel-Vinay M.C., Morel G. Localization of growth hormone receptor messenger RNA in human tissues. Endocrine. 1995;3:135–142. doi: 10.1007/BF02990065.
    1. Dehkhoda F., Lee C.M.M., Medina J., Brooks A.J. The growth hormone receptor: Mechanism of receptor activation, cell signaling, and physiological aspects. Front. Endocrinol. 2018;9:35. doi: 10.3389/fendo.2018.00035.
    1. Lanning N.J., Carter-Su C. Recent advances in growth hormone signaling. Rev. Endocr. Metab. Disord. 2006;7:225–235. doi: 10.1007/s11154-007-9025-5.
    1. Carter-Su C., Schwartz J., Argetsinger L.S. Growth hormone signaling pathways. Growth Horm. IGF Res. 2016;28:11–15. doi: 10.1016/j.ghir.2015.09.002.
    1. Kaplan S.A., Cohen P. Review: The somatomedin hypothesis 2007: 50 Years later. J. Clin. Endocrinol. Metab. 2007;92:4529–4535. doi: 10.1210/jc.2007-0526.
    1. Siddle K. Signalling by insulin and IGF receptors: Supporting acts and new players. J. Mol. Endocrinol. 2011;47:R1–R10. doi: 10.1530/JME-11-0022.
    1. Messina J. Comprehensive Physiology. John Wiley & Sons, Inc.; Hoboken, NJ, USA: 2010. Insulin as a growth-promoting hormone.
    1. Hong S., Mannan A.M., Inoki K. Evaluation of the nutrient-sensing mTOR pathway. Methods Mol. Biol. 2012;821:29–44. doi: 10.1007/978-1-61779-430-8_3.
    1. Forbes B.E., Blyth A.J., Wit J.M. Disorders of IGFs and IGF-1R signaling pathways. Mol. Cell. Endocrinol. 2020;518:111035. doi: 10.1016/j.mce.2020.111035.
    1. Rajaram S., Baylink D.J., Mohan S. Insulin-Like Growth Factor-Binding Proteins in Serum and Other Biological Fluids: Regulation and Functions. Endocr. Rev. 1997;18:801–831. doi: 10.1210/edrv.18.6.0321.
    1. Rosenzweig S.A. What’s new in the IGF-binding proteins? Growth Horm. IGF Res. 2004;14:329–336. doi: 10.1016/j.ghir.2004.02.003.
    1. Blum W.F., Albertsson-Wikland K., Rosberg S., Ranke M.B. Serum levels of insulin-like growth factor I (IGF-I) and IGF binding protein 3 reflect spontaneous growth hormone secretion. J. Clin. Endocrinol. Metab. 1993;76:1610–1616. doi: 10.1210/jcem.76.6.7684744.
    1. Maures T.J., Duan C. Structure, developmental expression, and physiological regulation of zebrafish IGF binding protein-1. Endocrinology. 2002;143:2722–2731. doi: 10.1210/endo.143.7.8905.
    1. Kajimura S., Aida K., Duan C. Understanding Hypoxia-Induced Gene Expression in Early Development: In Vitro and In Vivo Analysis of Hypoxia-Inducible Factor 1-Regulated Zebra Fish Insulin-Like Growth Factor Binding Protein 1 Gene Expression. Mol. Cell. Biol. 2006;26:1142–1155. doi: 10.1128/MCB.26.3.1142-1155.2006.
    1. O’Brien R.M., Noisin E.L., Suwanichkul A., Yamasaki T., Lucas P.C., Wang J.C., Powell D.R., Granner D.K. Hepatic nuclear factor 3- and hormone-regulated expression of the phosphoenolpyruvate carboxykinase and insulin-like growth factor-binding protein 1 genes. Mol. Cell. Biol. 1995;15:1747–1758. doi: 10.1128/MCB.15.3.1747.
    1. Veldhuis J.D., Johnson M.L. Cluster analysis: A simple, versatile, and robust algorithm for endocrine pulse detection. Am. J. Physiol. Endocrinol. Metab. 1986;250 doi: 10.1152/ajpendo.1986.250.4.E486.
    1. Veldhuis J.D., Carlson M.L., Johnson M.L. The pituitary gland secretes in bursts: Appraising the nature of glandular secretory impulses by simultaneous multiple-parameter deconvolution of plasma hormone concentrations. Proc. Natl. Acad. Sci. USA. 1987;84:7686–7690. doi: 10.1073/pnas.84.21.7686.
    1. Hartman M.L., Veldhuis J.D., Johnson M.L., Lee M.M., Alberti K.G.M.M., Samojlik E., Thorner M.O. Augmented growth hormone (GH) secretory burst frequency and amplitude mediate enhanced GH secretion during a two-day fast in normal men. J. Clin. Endocrinol. Metab. 1992;74:757–765. doi: 10.1210/jcem.74.4.1548337.
    1. Riedel M., Hoeft B., Blum W.F., von zur Mühlen A., Brabant G. Pulsatile growth hormone secretion in normal-weight and obese men: Differential metabolic regulation during energy restriction. Metabolism. 1995;44:605–610. doi: 10.1016/0026-0495(95)90117-5.
    1. Sakharova A.A., Horowitz J.F., Surya S., Goldenberg N., Harber M.P., Symons K., Barkan A. Role of growth hormone in regulating lipolysis, proteolysis, and hepatic glucose production during fasting. J. Clin. Endocrinol. Metab. 2008;93:2755–2759. doi: 10.1210/jc.2008-0079.
    1. Clemmons D.R., Klibanski A., Underwood L.E., McArthur J.W., Ridgway E.C., Beitins I.Z., Van Wyk J.J. Reduction of plasma immunoreactive somatomedin C during fasting in humans. J. Clin. Endocrinol. Metab. 1981;53:1247–1250. doi: 10.1210/jcem-53-6-1247.
    1. Merimee T.J., Zapf J., Froesch E.R. Insulin-Like Growth Factors in the Fed and Fasted States. J. Clin. Endocrinol. Metab. 1982;55:999–1002. doi: 10.1210/jcem-55-5-999.
    1. Underwood L.E., Thissen E.P., Ketelslegers J.M. Nutritional regulation of the insulin-like growth factors. Endocr. Rev. 1994;15:80–101. doi: 10.1210/edrv-15-1-80.
    1. Counts D.R., Gwirtsman H., Carlsson L.M.S., Lesem M. The effect of anorexia nervosa and refeeding on growth hormone-binding protein, the insulin-like growth factors (IGFs), and the IGF-binding proteins. J. Clin. Endocrinol. Metab. 1992;75:762–767. doi: 10.1210/jcem.75.3.1381372.
    1. Argente J., Caballo N., Barrios V., Muñoz M.T., Pozo J., Chowen J.A., Morandé G., Hernández M. Multiple Endocrine Abnormalities of the Growth Hormone and Insulin-Like Growth Factor Axis in Patients with Anorexia Nervosa: Effect of Short- and Long-Term Weight Recuperation 1. J. Clin. Endocrinol. Metab. 1997;82:2084–2092. doi: 10.1210/jcem.82.7.4090.
    1. Fazeli P.K., Klibanski A. Determinants of GH resistance in malnutrition. J. Endocrinol. 2014;220:R57. doi: 10.1530/JOE-13-0477.
    1. Clemmons D.R. Metabolic Actions of Insulin-Like Growth Factor-I in Normal Physiology and Diabetes. Endocrinol. Metab. Clin. N. Am. 2012;41:425–443. doi: 10.1016/j.ecl.2012.04.017.
    1. Baxter R.C., Bryson J.M., Turtle J.R. The effect of fasting on liver receptors for prolactin and growth hormone. Metabolism. 1981;30:1086–1090. doi: 10.1016/0026-0495(81)90052-4.
    1. Straus D.S., Takemoto C.D. Effect of fasting on insulin-like growth factor-I (IGF-I) and growth hormone receptor mRNA levels and IGF-I gene transcription in rat liver. Mol. Endocrinol. 1990;4:91–100. doi: 10.1210/mend-4-1-91.
    1. Huang Z., Huang L., Waters M.J., Chen C. Insulin and Growth Hormone Balance: Implications for Obesity. Trends Endocrinol. Metab. 2020;31:642–654. doi: 10.1016/j.tem.2020.04.005.
    1. Aimaretti G., Colao A., Corneli G., Pivonello R., Maccario M., Morrison K., Pflaum C.D., Strasburger C.J., Lombardi G., Ghigo E. The study of spontaneous GH secretion after 36-h fasting distinguishes between GH-deficient and normal adults. Clin. Endocrinol. (Oxf.) 1999;51:771–777. doi: 10.1046/j.1365-2265.1999.00885.x.
    1. Grottoli S., Gasco V., Mainolfi A., Beccuti G., Corneli G., Aimaretti G., Dieguez C., Casanueva F., Ghigo E. Growth hormone/insulin-like growth factor I axis, glucose metabolism, and lypolisis but not leptin show some degree of refractoriness to short-term fasting in acromegaly. J. Endocrinol. Investig. 2008;31:1103–1109. doi: 10.1007/BF03345660.
    1. Hartman M.L., Thorner M.O. Fasting-induced enhancement of pulsatile growth hormone (GH) secretion is rapidly abolished by refeeding; Proceedings of the 72nd Meeting of the Endocrine Society; Atlanta, GA, USA. 1 March 1990.
    1. Cornford A.S., Barkan A.L., Horowitz J.F. Rapid suppression of growth hormone concentration by overeating: Potential mediation by hyperinsulinemia. J. Clin. Endocrinol. Metab. 2011;96:824–830. doi: 10.1210/jc.2010-1895.
    1. Briard N., Rico-Gomez M., Guillaume V., Sauze N., Vuaroqueaux V., Dadoun F., Le Bouc Y., Oliver C., Dutour A. Hypothalamic mediated action of free fatty acid on growth hormone secretion in sheep. Endocrinology. 1998;139:4811–4819. doi: 10.1210/endo.139.12.6356.
    1. Casanueva F.F., Villanueva L., Dieguez C., Diaz Y., Cabranes J.A., Szoke B., Scanlon M.F., Schally A.V., Fernandez-Cruz A. Free fatty acids block growth hormone (GH) releasing hormone-stimulated gh secretion in man directly at the pituitary. J. Clin. Endocrinol. Metab. 1987;65:634–642. doi: 10.1210/jcem-65-4-634.
    1. Bang P., Brismar K., Rosenfeld R.G., Hall K. Fasting affects serum insulin-like growth factors (IGFs) and IGF-binding proteins differently in patients with noninsulin-dependent diabetes mellitus versus healthy nonobese and obese subjects. J. Clin. Endocrinol. Metab. 1994;78:960–967. doi: 10.1210/jcem.78.4.7512573.
    1. Frystyk J., Delhanty P.J.D., Skjærbæk C., Baxter R.C. Changes in the circulating IGF system during short-term fasting and refeeding in rats. Am. J. Physiol. Endocrinol. Metab. 1999;277 doi: 10.1152/ajpendo.1999.277.2.E245.
    1. Maccario M., Aimaretti G., Grottoli S., Gauna C., Tassone F., Corneli G., Rossetto R., Wu Z., Strasburger C.J., Ghigo E. Effects of 36 hour fasting on GH/IGF-I axis and metabolic parameters in patients with simple obesity. Comparison with normal subjects and hypopituitary patients with severe GH deficiency. Int. J. Obes. 2001;25:1233–1239. doi: 10.1038/sj.ijo.0801671.
    1. Luque R.M., Kineman R.D. Impact of obesity on the growth hormone axis: Evidence for a direct inhibitory effect of hyperinsulinemia on pituitary function. Endocrinology. 2006;147:2754–2763. doi: 10.1210/en.2005-1549.
    1. Gahete M.D., Córdoba-Chaćon J., Lin Q., Brüning J.C., Kahn C.R., Castaño J.P., Christian H., Luque R.M., Kineman R.D. Insulin and IGF-I inhibit GH synthesis and release in vitro and in vivo by separate mechanisms. Endocrinology. 2013;154:2410–2420. doi: 10.1210/en.2013-1261.
    1. Gasco V., Pagano L., Prodam F., Marzullo P., Ghigo E.A.G. In: Hypothalamic-Pituitary Disease and Obesity. Clemmons D., Attanasio A., editors. BioScentifica Ltd.; Bristol, UK: 2009. pp. 109–118.
    1. Berryman D.E., Glad C.A.M., List E.O., Johannsson G. The GH/IGF-1 axis in obesity: Pathophysiology and therapeutic considerations. Nat. Rev. Endocrinol. 2013;9:346–356. doi: 10.1038/nrendo.2013.64.
    1. Grottoli S., Gauna C., Tassone F., Aimaretti G., Corneli G., Wu Z., Strasburger C.J., Dieguez C., Casanueva F.F., Ghigo E., et al. Both fasting-induced leptin reduction and GH increase are blunted in Cushing’s syndrome and in simple obesity. Clin. Endocrinol. (Oxf.) 2003;58:220–228. doi: 10.1046/j.1365-2265.2003.01699.x.
    1. Bonert V.S., Elashoff J.D., Barnett P., Melmed S. Body mass index determines evoked growth hormone (GH) responsiveness in normal healthy male subjects: Diagnostic caveat for adult GH deficiency. J. Clin. Endocrinol. Metab. 2004;89:3397–3401. doi: 10.1210/jc.2003-032213.
    1. Qu X.D., Gaw Gonzalo I.T., Al Sayed M.Y., Cohan P., Christenson P.D., Swerdloff R.S., Kelly D.F., Wang C. Influence of body mass index and gender on growth hormone (GH) responses to GH-releasing hormone plus arginine and insulin tolerance tests. J. Clin. Endocrinol. Metab. 2005;90:1563–1569. doi: 10.1210/jc.2004-1450.
    1. Williams T., Berelowitz M., Joffe S.N., Thorner M.O., Rivier J., Vale W., Frohman L.A. Impaired Growth Hormone Responses to Growth Hormone–Releasing Factor in Obesity. N. Engl. J. Med. 1984;311:1403–1407. doi: 10.1056/NEJM198411293112203.
    1. Rasmussen M.H., Hvidberg A., Juul A., Main K.M., Gotfredsen A., Skakkebaek N.E., Hilsted J. Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects. J. Clin. Endocrinol. Metab. 1995;80:1407–1415. doi: 10.1210/jcem.80.4.7536210.
    1. De Marinis L., Bianchi A., Mancini A., Gentilella R., Perrelli M., Giampietro A., Porcelli T., Tilaro L., Fusco A., Valle D., et al. Growth Hormone Secretion and Leptin in Morbid Obesity before and after Biliopancreatic Diversion: Relationships with Insulin and Body Composition. J. Clin. Endocrinol. Metab. 2004;89:174–180. doi: 10.1210/jc.2002-021308.
    1. Yang J., Brown M.S., Liang G., Grishin N.V., Goldstein J.L. Identification of the Acyltransferase that Octanoylates Ghrelin, an Appetite-Stimulating Peptide Hormone. Cell. 2008;132:387–396. doi: 10.1016/j.cell.2008.01.017.
    1. Devesa J. The Complex World of Regulation of Pituitary Growth Hormone Secretion: The Role of Ghrelin, Klotho, and Nesfatins in It. Front. Endocrinol. (Lausanne) 2021;12 doi: 10.3389/fendo.2021.636403.
    1. Devesa J., Lima L., Tresguerres J.A.F. Neuroendocrine control of growth hormone secretion in humans. Trends Endocrinol. Metab. 1992;3:175–183. doi: 10.1016/1043-2760(92)90168-Z.
    1. Root A.W., Root M.J. Clinical pharmacology of human growth hormone and its secretagogues. Curr. Drug Targets. Immune. Endocr. Metabol. Disord. 2002;2:27–52. doi: 10.2174/1568005310202010027.
    1. Nakazato M., Murakami N., Date Y., Kojima M., Matsuo H., Kangawa K., Matsukura S. A role for ghrelin in the central regulation of feeding. Nature. 2001;409:194–198. doi: 10.1038/35051587.
    1. Kojima M., Kangawa K. Ghrelin: Structure and function. Physiol. Rev. 2005;85:495–522. doi: 10.1152/physrev.00012.2004.
    1. Malik S., McGlone F., Bedrossian D., Dagher A. Ghrelin Modulates Brain Activity in Areas that Control Appetitive Behavior. Cell Metab. 2008;7:400–409. doi: 10.1016/j.cmet.2008.03.007.
    1. Kanoski S.E., Fortin S.M., Ricks K.M., Grill H.J. Ghrelin signaling in the ventral hippocampus stimulates learned and motivational aspects of feeding via PI3K-Akt signaling. Biol. Psychiatry. 2013;73:915–923. doi: 10.1016/j.biopsych.2012.07.002.
    1. Yanagi S., Sato T., Kangawa K., Nakazato M. The Homeostatic Force of Ghrelin. Cell Metab. 2018;27:786–804. doi: 10.1016/j.cmet.2018.02.008.
    1. Gortan Cappellari G., Barazzoni R. Ghrelin forms in the modulation of energy balance and metabolism. Eat. Weight Disord. 2019;24:997–1013. doi: 10.1007/s40519-018-0599-6.
    1. Romere C., Duerrschmid C., Bournat J., Constable P., Jain M., Xia F., Saha P.K., Del Solar M., Zhu B., York B., et al. Asprosin, a Fasting-Induced Glucogenic Protein Hormone. Cell. 2016;165:566–579. doi: 10.1016/j.cell.2016.02.063.
    1. Duerrschmid C., He Y., Wang C., Li C., Bournat J.C., Romere C., Saha P.K., Lee M.E., Phillips K.J., Jain M., et al. Asprosin is a centrally acting orexigenic hormone. Nat. Med. 2017;23:1444–1453. doi: 10.1038/nm.4432.
    1. Prodam F., Me E., Riganti F., Gramaglia E., Bellone S., Baldelli R., Rapa A., Van Der Lely A.J., Bona G., Ghigo E., et al. The nutritional control of ghrelin secretion in humans: The effects of enteral vs. parenteral nutrition. Eur. J. Nutr. 2006;45:399–405. doi: 10.1007/s00394-006-0613-z.
    1. Prodam F., Monzani A., Ricotti R., Marolda A., Bellone S., Aimaretti G., Roccio M., Bona G. Systematic review of ghrelin response to food intake in pediatric age, from neonates to adolescents. J. Clin. Endocrinol. Metab. 2014;99:1556–1568. doi: 10.1210/jc.2013-4010.
    1. Müller T.D., Nogueiras R., Andermann M.L., Andrews Z.B., Anker S.D., Argente J., Batterham R.L., Benoit S.C., Bowers C.Y., Broglio F., et al. Ghrelin. Mol. Metab. 2015;4:437–460. doi: 10.1016/j.molmet.2015.03.005.
    1. Muller A.F., Lamberts S.W.J., Janssen J.A.M.J.L., Hofland L.J., Van Koetsveld P., Bidlingmaier M., Strasburger C.J., Ghigo E., Van der Lely A.J. Ghrelin drives GH secretion during fasting in man. Eur. J. Endocrinol. 2002;146:203–207. doi: 10.1530/eje.0.1460203.
    1. Koutkia P., Canavan B., Breu J., Johnson M.L., Grinspoon S.K. Nocturnal ghrelin pulsatility and response to growth hormone secretagogues in healthy men. Am. J. Physiol. Endocrinol. Metab. 2004;287 doi: 10.1152/ajpendo.00548.2003.
    1. Nass R., Farhy L.S., Liu J., Prudom C.E., Johnson M.L., Veldhuis P., Pezzoli S.S., Oliveri M.C., Gaylinn B.D., Geysen H.M., et al. Evidence for acyl-ghrelin modulation of growth hormone release in the fed state. J. Clin. Endocrinol. Metab. 2008;93:1988–1994. doi: 10.1210/jc.2007-2234.
    1. Broglio F., Prodam F., Riganti F., Gottero C., Destefanis S., Granata R., Muccioli G., Abribat T., van der Lely A.J., Ghigo E. The continuous infusion of acylated ghrelin enhances growth hormone secretion and worsens glucose metabolism in humans. J. Endocrinol. Investig. 2008;31:788–794. doi: 10.1007/BF03349259.
    1. Espelund U., Hansen T.K., Højlund K., Beck-Nielsen H., Clausen J.T., Hansen B.S., Ørskov H., Jørgensen J.O.L., Frystyk J. Fasting unmasks a strong inverse association between Ghrelin and Cortisol in serum: Studies in obese and normal-weight subjects. J. Clin. Endocrinol. Metab. 2005;90:741–746. doi: 10.1210/jc.2004-0604.
    1. Nørrelund H., Hansen T.K., Ørskov H., Hosoda H., Kojima M., Kangawa K., Weeke J., Møller N., Christiansen J.S., Jørgensen J.O.L. Ghrelin immunoreactivity in human plasma is suppressed by somatostatin. Clin. Endocrinol. (Oxf.) 2002;57:539–546. doi: 10.1046/j.1365-2265.2002.01649.x.
    1. Natalucci G., Riedl S., Gleiss A., Zidek T., Frisch H. Spontaneous 24-h ghrelin secretion pattern in fasting subjects: Maintenance of a meal-related pattern. Eur. J. Endocrinol. 2005;152:845–850. doi: 10.1530/eje.1.01919.
    1. Avram A.M., Jaffe C.A., Symons K.V., Barkan A.L. Endogenous circulating ghrelin does not mediate growth hormone rhythmicity or response to fasting. J. Clin. Endocrinol. Metab. 2005;90:2982–2987. doi: 10.1210/jc.2004-1785.
    1. Zhao T.J., Liang G., Li R.L., Xie X., Sleeman M.W., Murphy A.J., Valenzuela D.M., Yancopoulos G.D., Goldstein J.L., Brown M.S. Ghrelin O-acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice. Proc. Natl. Acad. Sci. USA. 2010;107:7467–7472. doi: 10.1073/pnas.1002271107.
    1. Goldstein J.L., Zhao T.J., Li R.L., Sherbet D.P., Liang G., Brown M.S. Surviving starvation: Essential role of the ghrelin-growth hormone axis. Cold Spring Harb. Symp. Quant. Biol. 2011;76:121–127. doi: 10.1101/sqb.2011.76.010447.
    1. Zhang Y., Fang F., Goldstein J.L., Brown M.S., Zhao T.J. Reduced autophagy in livers of fasted, fat-depleted, ghrelin-deficient mice: Reversal by growth hormone. Proc. Natl. Acad. Sci. USA. 2015;112:1226–1231. doi: 10.1073/pnas.1423643112.
    1. Ge X., Yang H., Bednarek M.A., Galon-Tilleman H., Chen P., Chen M., Lichtman J.S., Wang Y., Dalmas O., Yin Y., et al. LEAP2 Is an Endogenous Antagonist of the Ghrelin Receptor. Cell Metab. 2018;27:461–469. doi: 10.1016/j.cmet.2017.10.016.
    1. Mani B.K., Puzziferri N., He Z., Rodriguez J.A., Osborne-Lawrence S., Metzger N.P., Chhina N., Gaylinn B., Thorner M.O., Louise Thomas E., et al. LEAP2 changes with body mass and food intake in humans and mice. J. Clin. Investig. 2019;129:3909–3923. doi: 10.1172/JCI125332.
    1. Nelson D.L., Cox M.M. Lehninger Principles of Biochemistry. 7th ed. W.H. Freeman; New York, NY, USA: 2017.
    1. SINU—Società Italiana di Nutrizione Umana. [(accessed on 16 April 2021)]; Available online:
    1. Trumbo P., Schlicker S., Yates A.A., Poos M. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids. J. Am. Diet. Assoc. 2002;102:1621–1630. doi: 10.1016/S0002-8223(02)90346-9.
    1. Dietary Guidelines for Americans, 2020–2025 and Online Materials|Dietary Guidelines for Americans. [(accessed on 16 April 2021)]; Available online: .
    1. Dominici F.P., Turyn D. Growth hormone-induced alterations in the insulin-signaling system. Exp. Biol. Med. 2002;227:149–157. doi: 10.1177/153537020222700301.
    1. Oliveira C.R.P., Meneguz-Moreno R.A., Aguiar-Oliveira M.H., Barreto-Filho J.A.S. Emerging role of the GH/IGF-I on cardiometabolic control. Arq. Bras. Cardiol. 2011;97:434–439. doi: 10.1590/S0066-782X2011001400012.
    1. Chiarelli F., Giannini C., Mohn A. Growth, growth factors and diabetes. Eur. J. Endocrinol. 2004;151(Suppl. 3):U109–U117. doi: 10.1530/eje.0.151u109.
    1. LeRoith D., Yakar S. Mechanisms of disease: Metabolic effects of growth hormone and insulin-like growth factor 1. Nat. Clin. Pract. Endocrinol. Metab. 2007;3:302–310. doi: 10.1038/ncpendmet0427.
    1. Lebrun P., Van Obberghen E. SOCS proteins causing trouble in insulin action. Acta Physiol. (Oxf.) 2008;192:29–36. doi: 10.1111/j.1748-1716.2007.01782.x.
    1. Del Rincon J.P., Iida K., Gaylinn B.D., McCurdy C.E., Leitner J.W., Barbour L.A., Kopchick J.J., Friedman J.E., Draznin B., Thorner M.O. Growth hormone regulation of p85α expression and phosphoinositide 3-kinase activity in adipose tissue: Mechanism for growth hormone-mediated insulin resistance. Diabetes. 2007;56:1638–1646. doi: 10.2337/db06-0299.
    1. Barbour L.A., Rahman S.M., Gurevich I., Leitner J.W., Fischer S.J., Roper M.D., Knotts T.A., Vo Y., McCurdy C.E., Yakar S., et al. Increased P85α is a potent negative regulator of skeletal muscle insulin signaling and induces in vivo insulin resistance associated with growth hormone excess. J. Biol. Chem. 2005;280:37489–37494. doi: 10.1074/jbc.M506967200.
    1. Yuen K.C.J., Frystyk J., White D.K., Twickler T.B., Koppeschaar H.P.F., Harris P.E., Fryklund L., Murgatroyd P.R., Dunger D.B. Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone (GH) dose in adults with severe GH deficiency. Clin. Endocrinol. (Oxf.) 2005;63:428–436. doi: 10.1111/j.1365-2265.2005.02359.x.
    1. Hunter W.M., Willoughby J.M., Strong J.A. Plasma insulin and growth hormone during 22-hour fasts and after graded glucose loads in six healthy adults. J. Endocrinol. 1968;40:297–311. doi: 10.1677/joe.0.0400297.
    1. Roth J., Glick S.M., Yalow R.S., Berson S.A. Hypoglycemia: A potent stimulus to secretion of growth hormone. Science. 1963;140:987–988. doi: 10.1126/science.140.3570.987.
    1. Roth J., Glick S., Yalow R., Berson S. Secretion of human growth hormone: Physiologic and experimental modification. Metabolism. 1963;12:577–579.
    1. Yalow R.S., Goldsmith S.J., Berson S.A. Influence of physiologic fluctuations in plasma growth hormone on glucose tolerance. Diabetes. 1969;18:402–408. doi: 10.2337/diab.18.6.402.
    1. Penalva A., Burguera B., Cusahie X., Tresguerres J.A.F., Dieguez C., Casanueva F.F. Activation of cholinergic neurotransmission by pyridostigmine reverses the inhibitory effect of hyperglycemia on growth hormone (GH) releasing hormone-induced GH secretion in man: Does acute hyperglycemia act through hypothalamic release of somatostatin? Neuroendocrinology. 1989;49:551–554. doi: 10.1159/000125166.
    1. Masuda A., Shibasaki T., Nakahara M., Imaki T., Kiyosawa Y., Jibiki K., Demura H., Shizume K., Ling N. The effect of glucose on growth hormone (gh)-releasing hormone-mediated gh secretion in man. J. Clin. Endocrinol. Metab. 1985;60:523–526. doi: 10.1210/jcem-60-3-523.
    1. Gasperi M., Cecconi E., Grasso L., Bartalena L., Centoni R., Aimaretti G., Broglio F., Miccoli P., Marcocci C., Ghigo E., et al. GH secretion is impaired in patients with primary hyperparathyroidism. J. Clin. Endocrinol. Metab. 2002;87:1961–1964. doi: 10.1210/jcem.87.5.8451.
    1. Friend K., Iranmanesh A., Login I.S., Veldhuis J.D. Pyridostigmine treatment selectively amplifies the mass of GH secreted per burst without altering GH burst frequency, half-life, basal GH secretion or the orderliness of GH release. Eur. J. Endocrinol. 1997;137:377–386. doi: 10.1530/eje.0.1370377.
    1. Nakagawa E., Nagaya N., Okumura H., Enomoto M., Oya H., Ono F., Hosoda H., Kojima M., Kangawa K. Hyperglycaemia suppresses the secretion of ghrelin, a novel growth-hormone-releasing peptide: Responses to the intravenous and oral administration of glucose. Clin. Sci. 2002;103:325–328. doi: 10.1042/cs1030325.
    1. Shiiya T., Nakazato M., Mizuta M., Date Y., Mondal M.S., Tanaka M., Nozoe S.I., Hosoda H., Kangawa K., Matsukura S. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J. Clin. Endocrinol. Metab. 2002;87:240–244. doi: 10.1210/jcem.87.1.8129.
    1. Teff K.L., Elliott S.S., Tschöp M., Kieffer T.J., Rader D., Heiman M., Townsend R.R., Keim N.L., D’Alessio D., Havel P.J. Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. J. Clin. Endocrinol. Metab. 2004;89:2963–2972. doi: 10.1210/jc.2003-031855.
    1. Pena-Bello L., Pertega-Diaz S., Outeiriño-Blanco E., Garcia-Buela J., Tovar S., Sangiao-Alvarellos S., Dieguez C., Cordido F. Effect of oral glucose administration on rebound growth hormone release in normal and obese women: The role of adiposity, insulin sensitivity and ghrelin. PLoS ONE. 2015;10:e0121087. doi: 10.1371/journal.pone.0121087.
    1. Gottero C., Bellone S., Rapa A., van Koetsveld P., Vivenza D., Prodam F., Benso A., Destefanis S., Gauna C., Bellone J., et al. Standard light breakfast inhibits circulating ghrelin level to the same extent of oral glucose load in humans, despite different impact on glucose and insulin levels. J. Endocrinol. Investig. 2003;26:1203–1207. doi: 10.1007/BF03349158.
    1. Lucidi P., Murdolo G., Di Loreto C., De Cicco A., Parlanti N., Fanelli C., Santeusanio F., Bolli G.B., De Feo P. Ghrelin is not necessary for adequate hormonal counterregulation of insulin-induced hypoglycemia. Diabetes. 2002;51:2911–2914. doi: 10.2337/diabetes.51.10.2911.
    1. McCowen K.C., Maykel J.A., Bistrian B.R., Ling P.R. Circulating ghrelin concentrations are lowered by intravenous glucose or hyperinsulinemic euglycemic conditions in rodents. J. Endocrinol. 2002;175:R7–R11. doi: 10.1677/joe.0.175r007.
    1. Foster-Schubert K.E., Overduin J., Prudom C.E., Liu J., Callahan H.S., Gaylinn B.D., Thorner M.O., Cummings D.E. Acyl and total ghrelin are suppressed strongly by ingested proteins, weakly by lipids, and biphasically by carbohydrates. J. Clin. Endocrinol. Metab. 2008;93:1971–1979. doi: 10.1210/jc.2007-2289.
    1. Broglio F., Arvat E., Benso A., Gottero C., Muccioli G., Papotti M., van der Lely A.J., Deghenghi R., Ghigo E. Ghrelin, a Natural GH Secretagogue Produced by the Stomach, Induces Hyperglycemia and Reduces Insulin Secretion in Humans. J. Clin. Endocrinol. Metab. 2001;86:5083. doi: 10.1210/jcem.86.10.8098.
    1. Slavin J. Fiber and prebiotics: Mechanisms and health benefits. Nutrients. 2013;5:1417–1435. doi: 10.3390/nu5041417.
    1. Augustin L.S.A., Aas A.M., Astrup A., Atkinson F.S., Baer-Sinnott S., Barclay A.W., Brand-Miller J.C., Brighenti F., Bullo M., Buyken A.E., et al. Dietary fibre consensus from the international carbohydrate quality consortium (Icqc) Nutrients. 2020;12:2553. doi: 10.3390/nu12092553.
    1. Tungland B.C., Meyer D. Nondigestible oligo-and polysaccharides (dietary fiber): Their physiology and role in human health and food. Compr. Rev. Food Sci. Food Saf. 2002;1:90–109. doi: 10.1111/j.1541-4337.2002.tb00009.x.
    1. Cani P.D. Microbiota and metabolites in metabolic diseases. Nat. Rev. Endocrinol. 2019;15:69–70. doi: 10.1038/s41574-018-0143-9.
    1. Cani P.D. Targeting gut microbiota with a complex mix of dietary fibers improves metabolic diseases. Kidney Int. 2019;95:14–16. doi: 10.1016/j.kint.2018.11.012.
    1. Denny-Brown S., Stanley T.L., Grinspoon S.K., Makimura H. The association of macro- and micronutrient intake with growth hormone secretion. Growth Horm. IGF Res. 2012;22:102–107. doi: 10.1016/j.ghir.2012.03.001.
    1. Lopez M., Mohiuddin S. StatPearls. StatPearls Publishing; Treasure Island, FL, USA: 2021. Biochemistry, Essential Amino Acids.
    1. Griminger P., Scanes C.G. Avian Physiology. Springer; Berlin/Heidelberg, Germany: 1986. Protein Metabolism.
    1. World Health Organization . Obesity: Preventing and Managing the Global Epidemic. World Health Organization; Geneva, Switzerland: 2000.
    1. USDA. [(accessed on 20 April 2021)]; Available online:
    1. Chromiak J.A., Antonio J. Use of amino acids as growth hormone-releasing agents by athletes. Nutrition. 2002;18:657–661. doi: 10.1016/S0899-9007(02)00807-9.
    1. Knopf R.F., Conn J.W., Fajans S.S., Floyd J.C., Guntsche E.M., Rull J.A. Plasma Growth Hormone Response to Intravenous Administration of Amino Acids. J. Clin. Endocrinol. Metab. 1965;25:1140–1144. doi: 10.1210/jcem-25-8-1140.
    1. Alba-Roth J., Müller O.A., Schopohl J., Von Werder K. Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion. J. Clin. Endocrinol. Metab. 1988;67:1186–1189. doi: 10.1210/jcem-67-6-1186.
    1. Ghigo E., Aimaretti G., Corneli G. Diagnosis of adult GH deficiency. Growth Horm. IGF Res. 2008;18:1–16. doi: 10.1016/j.ghir.2007.07.004.
    1. Prodam F., Pagano L., Corneli G., Golisano G., Belcastro S., Busti A., Gasco V., Beccuti G., Grottoli S., Di Somma C., et al. Update on epidemiology, etiology, and diagnosis of adult growth hormone deficiency. J. Endocrinol. Investig. 2008;31:6–11.
    1. Gröschl M., Knerr I., Topf H.G., Schmid P., Rascher W., Rauh M. Endocrine responses to the oral ingestion of a physiological dose of essential amino acids in humans. J. Endocrinol. 2003;179:237–244. doi: 10.1677/joe.0.1790237.
    1. Collier S.R., Casey D.P., Kanaley J.A. Growth hormone responses to varying doses of oral arginine. Growth Horm. IGF Res. 2005;15:136–139. doi: 10.1016/j.ghir.2004.12.004.
    1. Welbourne T.C. Increased plasma bicarbonate and growth hormone after an oral glutamine load. Am. J. Clin. Nutr. 1995;61:1058–1061. doi: 10.1093/ajcn/61.5.1058.
    1. Isidori A., Lo Monaco A., Cappa M. A study of growth hormone release in man after oral administration of amino acids. Curr. Med. Res. Opin. 1981;7:475–481. doi: 10.1185/03007998109114287.
    1. Suminski R.R., Robertson R.J., Goss F.L., Arslanian S., Kang J., DaSilva S., Utter A.C., Metz K.F. Acute effect of amino acid ingestion and resistance exercise on plasma growth hormone concentration in young men. Int. J. Sport Nutr. Exerc. Metab. 1997;7:48–60. doi: 10.1123/ijsn.7.1.48.
    1. Lambert M.I., Hefer J.A., Millar R.P., Macfarlane P.W. Failure of commercial oral amino acid supplements to increase serum growth hormone concentrations in male body-builders. Int. J. Sport Nutr. 1993;3:298–305. doi: 10.1123/ijsn.3.3.298.
    1. Hickson J.F.J., Bucci L., Pivarnik J.M., Wolinsky I., Mcmahon J.C., Turner S.D. Ornithine ingestion and growth hormone release in bodybuilders. Nutr. Res. 1990;3:239.
    1. Merimee T.J., Rabinowitz D., Fineberg S.E. Arginine-Initiated Release of Human Growth Hormone. N. Engl. J. Med. 1969;280:1434–1438. doi: 10.1056/NEJM196906262802603.
    1. Tanaka K., Inoue S., Shiraki J., Shishido T., Saito M., Numata K., Takamura Y. Age-related decrease in plasma growth hormone: Response to growth hormone-releasing hormone, arginine, and l-dopa in obesity. Metabolism. 1991;40:1257–1262. doi: 10.1016/0026-0495(91)90025-R.
    1. Van Vught A.J.A.H., Nieuwenhuizen A.G., Brummer R.J.M., Westerterp-Plantenga M.S. Effects of oral ingestion of amino acids and proteins on the somatotropic axis. J. Clin. Endocrinol. Metab. 2008;93:584–590. doi: 10.1210/jc.2007-1784.
    1. Sellini M., Fierro A., Marchesi L., Manzo G., Giovannini C. Behavior of Basal Values and Circadian Rhythm of ACTH, Cortisol, PRL and GH in a High-Protein Diet. Boll. Soc. Ital. Biol. Sper. 1981;57:963–969.
    1. Galbo H., Christensen N.J., Mikines K.J., Sonne B., Hilsted J., Hagen C., Fahrenkrug J. The effect of fasting on the hormonal response to graded exercise. J. Clin. Endocrinol. Metab. 1981;52:1106–1112. doi: 10.1210/jcem-52-6-1106.
    1. Quirion A., Brisson G., De Carufel D., Laurencelle L., Therminarias A., Vogelaere P. Influence of exercise and dietary modifications on plasma human growth hormone, insulin and FFA. J Sport. Med. Phys. Fit. 1988;28:352–353.
    1. Fleddermann M., Demmelmair H., Grote V., Bidlingmaier M., Grimminger P., Bielohuby M., Koletzko B. Role of selected amino acids on plasma IGF-I concentration in infants. Eur. J. Nutr. 2017;56:613–620. doi: 10.1007/s00394-015-1105-9.
    1. Levine M.E., Suarez J.A., Brandhorst S., Balasubramanian P., Cheng C.W., Madia F., Fontana L., Mirisola M.G., Guevara-Aguirre J., Wan J., et al. Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab. 2014;19:407–417. doi: 10.1016/j.cmet.2014.02.006.
    1. Allen N., Appleby P., Davey G., Kaaks R., Rinaldi S., Key T. The associations of diet with serum insulin-like growth factor I and its main binding proteins in 292 women meat-eaters, vegetarians, and vegans. Cancer Epidemiol. Biomarkers Prev. 2002;11:1441–1448.
    1. Hoppe C., Udam T.R., Lauritzen L., Mølgaard C., Juul A., Michaelsen K.F. Animal protein intake, serum insulin-like growth factor I, and growth in healthy 2.5-y-old Danish children. Am. J. Clin. Nutr. 2004;80:447–452. doi: 10.1093/ajcn/80.2.447.
    1. Romo Ventura E., Konigorski S., Rohrmann S., Schneider H., Stalla G.K., Pischon T., Linseisen J., Nimptsch K. Association of dietary intake of milk and dairy products with blood concentrations of insulin-like growth factor 1 (IGF-1) in Bavarian adults. Eur. J. Nutr. 2020;59:1413–1420. doi: 10.1007/s00394-019-01994-7.
    1. Crowe F.L., Key T.J., Allen N.E., Appleby P.N., Roddam A., Overvad K., Grønbæk H., Tjønneland A., Halkjær J., Dossus L., et al. The association between diet and serum concentrations of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 in the European prospective investigation into cancer and nutrition. Cancer Epidemiol. Biomarkers Prev. 2009;18:1333–1340. doi: 10.1158/1055-9965.EPI-08-0781.
    1. Larsson S.C., Wolk K., Brismar K., Wolk A. Association of diet with serum insulin-like growth factor I in middle-aged and elderly men. Am. J. Clin. Nutr. 2005;81:1163–1167. doi: 10.1093/ajcn/81.5.1163.
    1. Norat T., Dossus L., Rinaldi S., Overvad K., Grønbæk H., Tjønneland A., Olsen A., Clavel-Chapelon F., Boutron-Ruault M.C., Boeing H., et al. Diet, serum insulin-like growth factor-I and IGF-binding protein-3 in European women. Eur. J. Clin. Nutr. 2007;61:91–98. doi: 10.1038/sj.ejcn.1602494.
    1. Beasley J.M., Gunter M.J., Lacroix A.Z., Prentice R.L., Neuhouser M.L., Tinker L.F., Vitolins M.Z., Strickler H.D. Associations of serum insulin-like growth factor-I and insulin-like growth factor-binding protein 3 levels with biomarker-calibrated protein, dairy product and milk intake in the Women’s Health Initiative. Br. J. Nutr. 2014;111:847–853. doi: 10.1017/S000711451300319X.
    1. Takahashi S., Kajikawa M., Umezawa T., Takahashi S., Kato H., Miura Y., Nam T., Noguchi T., Naito H. Effect of dietary proteins on the plasma immunoreactive insulin-like growth factor-1/somatomedin C concentration in the rat. Br. J. Nutr. 1990;63:521–534. doi: 10.1079/BJN19900139.
    1. Takenaka A., Oki N., Takahashi S.I., Noguchi T. Dietary restriction of single essential amino acids reduces plasma insulin-like growth factor-I (IGF-I) but does not affect plasma IGF-binding protein-1 in rats. J. Nutr. 2000;130:2910–2914. doi: 10.1093/jn/130.12.2910.
    1. Thissen J.P., Pucilowska J.B., Underwood L.E. Differential regulation of insulin-like growth factor I (IGF-I) and IGF Binding Protein-1 messenger ribonucleic acids by amino acid availability and growth hormone in rat hepatocyte primary culture. Endocrinology. 1994;134:1570–1576. doi: 10.1210/endo.134.3.7509741.
    1. Philipps A.F., Dvořák B., Kling P.J., Grille J.G., Koldovský O. Absorption of Milk-Borne Insulin-Like Growth Factor-I into Portal Blood of Suckling Rats. J. Pediatr. Gastroenterol. Nutr. 2000;31:128–135. doi: 10.1097/00005176-200008000-00008.
    1. Fürstenberger G., Senn H.J. Insulin-like growth factors and cancer. Lancet Oncol. 2002;3:298–302. doi: 10.1016/S1470-2045(02)00731-3.
    1. Keller U. Nutritional Laboratory Markers in Malnutrition. J. Clin. Med. 2019;8:775. doi: 10.3390/jcm8060775.
    1. Paszynska E., Dmitrzak-Weglarz M., Slopien A., Tyszkiewicz-Nwafor M., Rajewski A. Salivary and serum insulin-like growth factor (IGF-1) assays in anorexic patients. World J. Biol. Psychiatry. 2016;17:615–621. doi: 10.3109/15622975.2015.1023356.
    1. Fontana L., Partridge L. Promoting health and longevity through diet: From model organisms to humans. Cell. 2015;161:106–118. doi: 10.1016/j.cell.2015.02.020.
    1. Brandhorst S., Choi I.Y., Wei M., Cheng C.W., Sedrakyan S., Navarrete G., Dubeau L., Yap L.P., Park R., Vinciguerra M., et al. A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan. Cell Metab. 2015;22:86–99. doi: 10.1016/j.cmet.2015.05.012.
    1. Tremblay F., Lavigne C., Jacques H., Marette A. Role of dietary proteins and amino acids in the pathogenesis of insulin resistance. Annu. Rev. Nutr. 2007;27:293–310. doi: 10.1146/annurev.nutr.25.050304.092545.
    1. Tucker L.A., Erickson A., Lecheminant J.D., Bailey B.W. Dairy Consumption and Insulin Resistance: The Role of Body Fat, Physical Activity, and Energy Intake. J. Diabetes Res. 2015;2015 doi: 10.1155/2015/206959.
    1. Melnik B.C., John S.M., Schmitz G. Milk is not just food but most likely a genetic transfection system activating mTORC1 signaling for postnatal growth. Nutr. J. 2013;12:103. doi: 10.1186/1475-2891-12-103.
    1. Orgeron M.L., Stone K.P., Wanders D., Cortez C.C., Van N.T., Gettys T.W. Progress in Molecular Biology and Translational Science. Volume 121. Elsevier B.V.; Amsterdam, The Netherlands: 2014. The impact of dietary methionine restriction on biomarkers of metabolic health; pp. 351–376.
    1. McCarty M.F., Barroso-Aranda J., Contreras F. The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy. Med. Hypotheses. 2009;72:125–128. doi: 10.1016/j.mehy.2008.07.044.
    1. AsghariHanjani N., Vafa M. The role of IGF-1 in obesity, cardiovascular disease, and cancer. Med. J. Islam. Repub. Iran. 2019;33 doi: 10.47176/mjiri.33.56.
    1. Le Marchand-Brustel Y., Heydrick S.J., Jullien D., Gautier N., Van Obberghen E. Effect of insulin and insulin-like growth factor-1 on glucose transport and its transporters in soleus muscle of lean and obese mice. Metabolism. 1995;44:18–23. doi: 10.1016/0026-0495(95)90216-3.
    1. Gjedsted J., Gormsen L.C., Nielsen S., Schmitz O., Djurhuus C.B., Keiding S., Ørskov H., Tønnesen E., Møller N. Effects of a 3-day fast on regional lipid and glucose metabolism in human skeletal muscle and adipose tissue. Acta Physiol. 2007;191:205–216. doi: 10.1111/j.1748-1716.2007.01740.x.
    1. Wurzburger M.I., Prelevic G.M., Sonksen P.H., Balint-Peric L.A., Wheeler M. The effect of recombinant human growth hormone on regulation of growth hormone secretion and blood glucose in insulin-dependent diabetes. J. Clin. Endocrinol. Metab. 1993;77:267–272. doi: 10.1210/jcem.77.1.8325951.
    1. Li R., Ferreira M., Cooke M., La Bounty P., Campbell B., Greenwood M., Willoughby D., Kreider R. Co-ingestion of carbohydrate with branched-chain amino acids or L-leucine does not preferentially increase serum IGF-1 and expression of myogenic-related genes in response to a single bout of resistance exercise. Amino Acids. 2015;47:1203–1213. doi: 10.1007/s00726-015-1947-8.
    1. Church D.D., Schwarz N.A., Spillane M.B., McKinley-Barnard S.K., Andre T.L., Ramirez A.J., Willoughby D.S. l-Leucine Increases Skeletal Muscle IGF-1 but Does Not Differentially Increase Akt/mTORC1 Signaling and Serum IGF-1 Compared to Ursolic Acid in Response to Resistance Exercise in Resistance-Trained Men. J. Am. Coll. Nutr. 2016;35:627–638. doi: 10.1080/07315724.2015.1132019.
    1. Biagetti B., Herance J.R., Ferrer R., Aulinas A., Palomino-Schätzlein M., Mesa J., Castaño J.P., Luque R.M., Simó R. Metabolic Fingerprint of Acromegaly and its Potential Usefulness in Clinical Practice. J. Clin. Med. 2019;8:1549. doi: 10.3390/jcm8101549.
    1. Mastrangelo A., Martos-Moreno G., Rupérez F.J., Chowen J.A., Barbas C., Argente J. Metabolomics changes in patients with PAPP-A2 deficiency in response to rhIGF1 treatment. Growth Horm. IGF Res. 2018;42–43:28–31. doi: 10.1016/j.ghir.2018.08.002.
    1. Sawa R., Nishida H., Yamamoto Y., Wake I., Kai N., Kikkawa U., Okimura Y. Growth hormone and Insulin-like growth factor-I (IGF-I) modulate the expression of L-type amino acid transporters in the muscles of spontaneous dwarf rats and L6 and C2C12 myocytes. Growth Horm. IGF Res. 2018;42–43:66–73. doi: 10.1016/j.ghir.2018.09.002.
    1. Iqbal J., Hussain M.M. Intestinal lipid absorption. Am. J. Physiol. Endocrinol. Metab. 2009;296:E1183–E1194. doi: 10.1152/ajpendo.90899.2008.
    1. Quabbe H.J., Bratzke H.J., Siegers U., Elban K. Studies on the relationship between plasma free fatty acids and growth hormone secretion in man. J. Clin. Investig. 1972;51:2388–2398. doi: 10.1172/JCI107051.
    1. Moller N., Jorgensen J.O.L., Schmitz O., Moller J., Christiansen J.S., Alberti K.G.M.M., Orskov H. Effects of a growth hormone pulse on total and forearm substrate fluxes in humans. Am. J. Physiol. Endocrinol. Metab. 1990;258 doi: 10.1152/ajpendo.1990.258.1.E86.
    1. Neely R.D.G., Rooney D.P., Bell P.M., Bell N.P., Sheridan B., Atkinson A.B., Trimble E.R. Influence of growth hormone on glucose-glucose 6-phosphate cycle and insulin action in normal humans. Am. J. Physiol. Endocrinol. Metab. 1992;263 doi: 10.1152/ajpendo.1992.263.5.E980.
    1. Santomauro A.T.M.G., Boden G., Silva M.E.R., Rocha D.M., Santos R.F., Ursich M.J.M., Strassmann P.G., Wajchenberg B.L. Overnight lowering of free fatty acids with acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects. Diabetes. 1999;48:1836–1841. doi: 10.2337/diabetes.48.9.1836.
    1. Zachmann M., Fernandez F., Tassinari D., Thakker R., Prader A. Anthropometric measurements in patients with growth hormone deficiency before treatment with human growth hormone. Eur. J. Pediatr. 1980;133:277–282. doi: 10.1007/BF00496089.
    1. Salomon F., Cuneo R.C., Hesp R., Sönksen P.H. The Effects of Treatment with Recombinant Human Growth Hormone on Body Composition and Metabolism in Adults with Growth Hormone Deficiency. N. Engl. J. Med. 1989;321:1797–1803. doi: 10.1056/NEJM198912283212605.
    1. Davidson M.B. Effect of growth hormone on carbohydrate and lipid metabolism. Endocr. Rev. 1987;8:115–131. doi: 10.1210/edrv-8-2-115.
    1. Kreitschmann-Andermahr I., Suarez P., Jennings R., Evers N., Brabant G. GH/IGF-I regulation in obesity—Mechanisms and practical consequences in children and adults. Horm. Res. Paediatr. 2010;73:153–160. doi: 10.1159/000284355.
    1. Fuccella L.M., Goidaniga G., Lovisolo P., Maggi E., Musatti L., Mandelli V., Sirtori C.R. Inhibition of lipolysis by nicotinic acid and by acipimox. Clin. Pharmacol. Ther. 1980;28:790–795. doi: 10.1038/clpt.1980.236.
    1. Cordido F., Alvarez-Castro P., Isidro M.L., Casanueva F.F., Dieguez C. Comparison between insulin tolerance test, growth hormone (GH)-releasing hormone (GHRH), GHRH plus acipimox and GHRH plus GH-releasing peptide-6 for the diagnosis of adult GH deficiency in normal subjects, obese hypopituitary patients. Eur. J. Endocrinol. 2003;149:117–122. doi: 10.1530/eje.0.1490117.
    1. Glass A.R., Burman K.D., Dahms W.T., Boehm T.M. Endocrine function in human obesity. Metabolism. 1981;30:89–104. doi: 10.1016/0026-0495(81)90224-9.
    1. Peino R., Cordido F., Peñalva A., Alvarez C.V., Dieguez C., Casanueva F.F. Acipimox-mediated plasma free fatty acid depression per se stimulates growth hormone (GH) secretion in normal subjects and potentiates the response to other GH-releasing stimuli. J. Clin. Endocrinol. Metab. 1996;81:909–913. doi: 10.1210/jcem.81.3.8772549.
    1. Imaki T., Shibasaki T., Masuda A., Hotta M., Yamauchi N., Demura H., Shizume K., Wakabayashi I., Ling N. The effect of glucose and free fatty acids on growth hormone (gh)-releasing factor-mediated gh secretion in rats. Endocrinology. 1986;118:2390–2394. doi: 10.1210/endo-118-6-2390.
    1. Casanueva F.F. Physiology of growth hormone secretion and action. Endocrinol. Metab. Clin. N. Am. 1992;21:483–517. doi: 10.1016/S0889-8529(18)30199-3.
    1. Iranmanesh A., Veldhuis J. Clinical pathophysiology of the somatotropic (GH) axis in adults. Endocrinol. Metab. Clin. North Am. 1992;21:783–816. doi: 10.1016/S0889-8529(18)30189-0.
    1. Jenkins R.C., Ross R.J.M. Acquired growth hormone resistance in catabolic states. Baillieres. Clin. Endocrinol. Metab. 1996;10:411–419. doi: 10.1016/S0950-351X(96)80545-3.
    1. Scanlon M.F., Issa B.G., Dieguez C. Regulation of growth hormone secretion. Horm. Res. Paediatr. 1996;46:149–154. doi: 10.1159/000185014.
    1. Bolinder J., Lindblad A., Engfeldt P., Arner P. Studies of acute effects of insulin-like growth factors I and II in human fat cells. J. Clin. Endocrinol. Metab. 1987;65:732–737. doi: 10.1210/jcem-65-4-732.
    1. Pratipanawatr T., Pratipanawatr W., Rosen C., Berria R., Bajaj M., Cusi K., Mandarino L., Kashyap S., Belfort R., DeFronzo R.A. Effect of IGF-I on FFA and glucose metabolism in control and type 2 diabetic subjects. Am. J. Physiol. Endocrinol. Metab. 2002;282 doi: 10.1152/ajpendo.00335.2001.
    1. Fang X.L., Shu G., Zhang Z.Q., Wang S.B., Zhu X.T., Gao P., Xi Q.Y., Zhang Y.L., Jiang Q.Y. Roles of α-linolenic acid on IGF-I secretion and GH/IGF system gene expression in porcine primary hepatocytes. Mol. Biol. Rep. 2012;39:10987–10996. doi: 10.1007/s11033-012-2000-6.
    1. Yen P.M., Tashjian A.H. Short chain fatty acids increase prolactin and growth hormone production and alter cell morphology in the GH3 strain of rat pituitary cells. Endocrinology. 1981;109:17–22. doi: 10.1210/endo-109-1-17.
    1. Kato S.I., Sato K., Chida H., Roh S.G., Ohwada S., Sato S., Guilloteau P., Katoh K. Effects of Na-butyrate supplementation in milk formula on plasma concentrations of GH and insulin, and on rumen papilla development in calves. J. Endocrinol. 2011;211:241–248. doi: 10.1530/JOE-11-0299.
    1. Ishiwata H., Nagano M., Sasaki Y., Chen C., Katoh K. Short-chain fatty acids inhibit the release and content of growth hormone in anterior pituitary cells of the goat. Gen. Comp. Endocrinol. 2000;118:400–406. doi: 10.1006/gcen.2000.7468.
    1. Wang J.F., Fu S.P., Li S.N., Hu Z.M., Xue W.J., Li Z.Q., Huang B.X., Lv Q.K., Liu J.X., Wang W. Short-chain fatty acids inhibit growth hormone and prolactin gene transcription via cAMP/PKA/CREB signaling pathway in dairy cow anterior pituitary cells. Int. J. Mol. Sci. 2013;14:21474–21488. doi: 10.3390/ijms141121474.
    1. Fu S.P., Liu B.R., Wang J.F., Xue W.J., Liu H.M., Zeng Y.L., Huang B.X., Li S.N., Lv Q.K., Wang W., et al. β-hydroxybutyric acid inhibits growth hormone-releasing hormone synthesis and secretion through the GPR109A/extracellular signal-regulated 1/2 signalling pathway in the hypothalamus. J. Neuroendocrinol. 2015;27:212–222. doi: 10.1111/jne.12256.
    1. Pérez-Fernandez R., Alonso M., Segura C., Muñoz I., García-Caballero T., Diéguez C. Vitamin D receptor gene expression in human pituitary gland. Life Sci. 1996;60:35–42. doi: 10.1016/S0024-3205(96)00586-3.
    1. Giordano M., Godi M., Mellone S., Petri A., Vivenza D., Tiradani L., Carlomagno Y., Ferrante D., Arrigo T., Corneli G., et al. A functional common polymorphism in the vitamin D-responsive element of the GH1 promoter contributes to isolated growth hormone deficiency. J. Clin. Endocrinol. Metab. 2008;93:1005–1012. doi: 10.1210/jc.2007-1918.
    1. Seoane S., Perez-Fernandez R. The vitamin D receptor represses transcription of the pituitary transcription factor Pit-1 gene without involvement of the retinoid X receptor. Mol. Endocrinol. 2006;20:735–748. doi: 10.1210/me.2005-0253.
    1. Ameri P., Giusti A., Boschetti M., Murialdo G., Minuto F., Ferone D. Interactions between vitamin D and IGF-I: From physiology to clinical practice. Clin. Endocrinol. (Oxf.) 2013;79:457–463. doi: 10.1111/cen.12268.
    1. Keisala T., Minasyan A., Lou Y.R., Zou J., Kalueff A.V., Pyykkö I., Tuohimaa P. Premature aging in vitamin D receptor mutant mice. J. Steroid Biochem. Mol. Biol. 2009;115:91–97. doi: 10.1016/j.jsbmb.2009.03.007.
    1. Ciresi A., Giordano C. Vitamin D across growth hormone (GH) disorders: From GH deficiency to GH excess. Growth Horm. IGF Res. 2017;33:35–42. doi: 10.1016/j.ghir.2017.02.002.
    1. Robson H., Siebler T., Shalet S.M., Williams G.R. Interactions between GH, IGF-I, glucocorticoids, and thyroid hormones during skeletal growth. Pediatr. Res. 2002;52:137–147. doi: 10.1203/00006450-200208000-00003.
    1. Song Y., Kato S., Fleet J.C. Vitamin D receptor (VDR) knockout mice reveal VDR-independent regulation of intestinal calcium absorption and ECaC2 and calbindin D9k mRNA. J. Nutr. 2003;133:374–380. doi: 10.1093/jn/133.2.374.
    1. Liao L., Chen X., Wang S., Parlow A.F., Xu J. Steroid Receptor Coactivator 3 Maintains Circulating Insulin-Like Growth Factor I (IGF-I) by Controlling IGF-Binding Protein 3 Expression. Mol. Cell. Biol. 2008;28:2460–2469. doi: 10.1128/MCB.01163-07.
    1. Wei S., Tanaka H., Kubo T., Ono T., Kanzaki S., Seino Y. Growth hormone increases serum 1,25-dihydroxyvitamin D levels and decreases 24,25-dihydroxyvitamin D levels in children with growth hormone deficiency. Eur. J. Endocrinol. 1997;136:45–51. doi: 10.1530/eje.0.1360045.
    1. Halhali A., Díaz L., Sánchez I., Garabédian M., Bourges H., Larrea F. Effects of IGF-I on 1,25-dihydroxyvitamin D3 synthesis by human placenta in culture. Mol. Hum. Reprod. 1999;5:771–776. doi: 10.1093/molehr/5.8.771.
    1. Guibourdenche J., Djakouré C., Porquet D., Pagésy P., Rochette-Egly C., Peillon F., Li J.Y., Evain-Brion D. Retinoic acid stimulates growth hormone synthesis in human somatotropic adenoma cells: Characterization of its nuclear receptors. J. Cell. Biochem. 1997;65:25–31. doi: 10.1002/(SICI)1097-4644(199704)65:1<25::AID-JCB3>;2-0.
    1. Prodam F., Caputo M., Mele C., Marzullo P., Aimaretti G. Insights into non-classic and emerging causes of hypopituitarism. Nat. Rev. Endocrinol. 2021;17:114–129. doi: 10.1038/s41574-020-00437-2.
    1. Djakoure C., Guibourdenche J., Porquet D., Pagesy P., Peillon F., Li J.Y., Evain-Brion D. Vitamin A and retinoic acid stimulate within minutes cAMP release and growth hormone secretion in human pituitary cells. J. Clin. Endocrinol. Metab. 1996;81:3123–3126. doi: 10.1210/jcem.81.8.8768885.
    1. Murray M., Butler A.M., Fiala-Beer E., Su G.M. Phospho-STAT5 accumulation in nuclear fractions from vitamin A-deficient rat liver. FEBS Lett. 2005;579:3669–3673. doi: 10.1016/j.febslet.2005.05.052.
    1. Raifen R., Altman Y., Zadik Z. Vitamin A levels and growth hormone axis. Horm. Res. Paediatr. 1996;46:279–281. doi: 10.1159/000185101.
    1. Evain-Brion D., Fjellestad-Paulsen A., Czernichow P., Porquet D., Thérond P., Grenèche M.O., François L. Vitamin A deficiency and nocturnal growth hormone secretion in short children. Lancet. 1994;343:87–88. doi: 10.1016/S0140-6736(94)90819-2.
    1. Mohn A., Di Marzio D., Giannini C., Capanna R., Marcovecchio M., Chiarelli F. Alterations in the oxidant-antioxidant status in prepubertal children with growth hormone deficiency: Effect of growth hormone replacement therapy. Clin. Endocrinol. (Oxf.) 2005;63:537–542. doi: 10.1111/j.1365-2265.2005.02378.x.
    1. Ren S.G., Melmed S. Pyridoxal phosphate inhibits pituitary cell proliferation and hormone secretion. Endocrinology. 2006;147:3936–3942. doi: 10.1210/en.2005-1219.
    1. Báez-Saldaña A., Gutiérrez-Ospina G., Chimal-Monroy J., Fernandez-Mejia C., Saavedra R. Biotin deficiency in mice is associated with decreased serum availability of insulin-like growth factor-I. Eur. J. Nutr. 2009;48:137–144. doi: 10.1007/s00394-009-0773-8.
    1. Waters M.J., Shang C.A., Behncken S.N., Tam S.P., Li H., Shen B., Lobie P.E. Growth hormone as a cytokine. Clin. Exp. Pharmacol. Physiol. 1999;26:760–764. doi: 10.1046/j.1440-1681.1999.03129.x.
    1. Roman-Garcia P., Quiros-Gonzalez I., Mottram L., Lieben L., Sharan K., Wangwiwatsin A., Tubio J., Lewis K., Wilkinson D., Santhanam B., et al. Vitamin B12-dependent taurine synthesis regulates growth and bone mass. J. Clin. Investig. 2014;124:2988–3002. doi: 10.1172/JCI72606.
    1. Kamenický P., Mazziotti G., Lombès M., Giustina A., Chanson P. Growth hormone, insulin-like growth factor-1, and the kidney: Pathophysiological and clinical implications. Endocr. Rev. 2014;35:234–281. doi: 10.1210/er.2013-1071.
    1. Feld S., Hirschberg R. Growth Hormone, the Insulin-Like Growth Factor System, and the Kidney. Endocr. Rev. 1996;17:423–480. doi: 10.1210/edrv-17-5-423.
    1. McCormick S.D., Bradshaw D. Hormonal control of salt and water balance in vertebrates. Gen. Comp. Endocrinol. 2006;147:3–8. doi: 10.1016/j.ygcen.2005.12.009.
    1. Rosen T., Bosaeus I., Tolli J., Lindstedt G., Bengtsson B.A. Increased body fat mass and decreased extracellular fluid volume in adults with growth hormone deficiency. Clin. Endocrinol. 1993;38:63–71. doi: 10.1111/j.1365-2265.1993.tb00974.x.
    1. Dimke H., Flyvbjerg A., Frische S. Acute and chronic effects of growth hormone on renal regulation of electrolyte and water homeostasis. Growth Horm. IGF Res. 2007;17:353–368. doi: 10.1016/j.ghir.2007.04.008.
    1. Ikkos D., Luft R., Sjogren B. Body water and sodium in patients with acromegaly. J. Clin. Investig. 1954;33:989–994. doi: 10.1172/JCI102977.
    1. Flyvbjerg A., Dørup I., Everts M.E., Ørskov H. Evidence that potassium deficiency induces growth retardation through reduced circulating levels of growth hormone and insulin-like growth factor I. Metabolism. 1991;40:769–775. doi: 10.1016/0026-0495(91)90001-D.
    1. Flyvbjerg A., Marshall S.M., Frystyk J., Rasch R., Bornfeldt K.E., Arnqvist H., Jensen P.K., Pallesen G., Orskov H. Insulin-like growth factor I in initial renal hypertrophy in potassium- depleted rats. Am. J. Physiol. Ren. Fluid Electrolyte Physiol. 1992;262 doi: 10.1152/ajprenal.1992.262.6.F1023.
    1. Zivadinovic D., Tomić M., Yuan D., Stojilkovic S.S. Cell-type specific messenger functions of extracellular calcium in the anterior pituitary. Endocrinology. 2002;143:445–455. doi: 10.1210/endo.143.2.8637.
    1. Nussinovitch I. Tive supervision enhance. Endocrinology. 2018;159:4043–4055. doi: 10.1210/en.2018-00743.
    1. Coiro V., Volpi R., Capretti L., Finardi L., Magotti M.G., Manfredi G., Chiodera P., Jotti G.S. Inhibition of growth hormone secretion in mild primary hyperparathyroidism. Horm. Res. 2004;62:88–91. doi: 10.1159/000079613.
    1. Romoli R., Lania A., Mantovani G., Corbetta S., Persani L., Spada A. Expression of Calcium-Sensing Receptor and Characterization of Intracellular Signaling in Human Pituitary Adenomas1. J. Clin. Endocrinol. Metab. 1999;84:2848–2853. doi: 10.1210/jcem.84.8.5922.
    1. Ikema S., Horikawa R., Nakano M., Yokouchi K., Yamazaki H., Tanaka T., Tanae A. Growth and metabolic disturbances in a patient with total parenteral nutrition: A case of hypercalciuric hypercalcemia. Endocr. J. 2000;47 doi: 10.1507/endocrj.47.SupplMarch_S137.
    1. Fleet J.C., Bruns M.E., Hock J.M., Wood R.J. Growth hormone and parathyroid hormone stimulate intestinal calcium absorption in aged female rats. Endocrinology. 1994;134:1755–1760. doi: 10.1210/endo.134.4.8137740.
    1. Hoenderop J.G., Müller D., Van Der Kemp A.W., Hartog A., Suzuki M., Ishibashi K., Imai M., Sweep F., Willems P.H., Van Os C.H., et al. Calcitriol controls the epithelial calcium channel in kidney. J. Am. Soc. Nephrol. 2001;12:1342–1349. doi: 10.1681/ASN.V1271342.
    1. Kamenický P., Blanchard A., Gauci C., Salenave S., Letierce A., Lombès M., Brailly-Tabard S., Azizi M., Prié D., Souberbielle J.C., et al. Pathophysiology of renal calcium handling in acromegaly: What lies behind hypercalciuria? J. Clin. Endocrinol. Metab. 2012;97:2124–2133. doi: 10.1210/jc.2011-3188.
    1. Halloran B.P., Spencer E.M. Dietary phosphorus and 1,25-dihydroxyvitamin d metabolism: Influence of insulin-like growth factor i. Endocrinology. 1988;123:1225–1229. doi: 10.1210/endo-123-3-1225.
    1. Harbison M.D., Gertner J.M. Permissive action of growth hormone on the renal response to dietary phosphorus deprivation. J. Clin. Endocrinol. Metab. 1990;70:1035–1040. doi: 10.1210/jcem-70-4-1035.
    1. Saggese G., Baroncelli G.I., Federico G., Bertelloni S. Effects of growth hormone on phosphocalcium homeostasis and bone metabolism. Horm. Res. Paediatr. 1995;44:55–63. doi: 10.1159/000184675.
    1. Efthymiadou A., Kritikou D., Mantagos S., Chrysis D. The effect of GH treatment on serum FGF23 and Klotho in GH-deficient children. Eur. J. Endocrinol. 2016;174:473–479. doi: 10.1530/EJE-15-1018.
    1. Hirschberg R., Brunori G., Kopple J.D., Guler H.P. Effects of insulin-like growth factor I on renal function in normal men. Kidney Int. 1993;43:387–397. doi: 10.1038/ki.1993.57.
    1. Giordano M., DeFronzo R.A. Acute effect of human recombinant insulin-like growth factor I on renal function in humans. Nephron. 1995;71:10–15. doi: 10.1159/000188667.
    1. Woda C.B., Halaihel N., Wilson P.V., Haramati A., Levi M., Mulroney S.E. Regulation of renal NaPi-2 expression and tubular phosphate reabsorption by growth hormone in the juvenile rat. Am. J. Physiol. Ren. Physiol. 2004;287 doi: 10.1152/ajprenal.00357.2002.
    1. Shimada T., Kakitani M., Yamazaki Y., Hasegawa H., Takeuchi Y., Fujita T., Fukumoto S., Tomizuka K., Yamashita T. Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J. Clin. Investig. 2004;113:561–568. doi: 10.1172/JCI200419081.
    1. Schmid C., Neidert M.C., Tschopp O., Sze L., Bernays R.L. Growth hormone and Klotho. J. Endocrinol. 2013;219:R37–R57. doi: 10.1530/JOE-13-0285.
    1. Narayanan N., Lussier B., French M., Moor B., Kraicer J. Growth hormone-releasing factor-sensitive adenylate cyclase system of purified somatotrophs: Effects of guanine nucleotides, somatostatin, calcium, and magnesium. Endocrinology. 1989;124:484–495. doi: 10.1210/endo-124-1-484.
    1. Dørup I., Flyvbjerg A., Everts M.E., Clausen T. Role of insulin-like growth factor-1 and growth hormone in growth inhibition induced by magnesium and zinc deficiencies. Br. J. Nutr. 1991;66:505–521. doi: 10.1079/BJN19910051.
    1. Henneman P.H., Forbes A.P., Moldawer M., Dempsey E.F., Carroll E.L. Effects of human growth hormone in man. J. Clin. Investig. 1960;39:1223–1238. doi: 10.1172/JCI104138.
    1. Mahlbacher K., Sicuro A., Gerber H., Hulter H.N., Krapf R. Growth hormone corrects acidosis-induced renal nitrogen wasting and renal phosphate depletion and attenuates renal magnesium wasting in humans. Metabolism. 1999;48:763–770. doi: 10.1016/S0026-0495(99)90177-4.
    1. Estívariz C.F., Ziegler T.R. Nutrition and the Insulin-Like Growth Factor System. Endocrine. 1997;7:65–71. doi: 10.1007/BF02778066.
    1. Millward D.J. Nutrition, infection and stunting: The roles of deficiencies of individual nutrients and foods, and of inflammation, as determinants of reduced linear growth of children. Nutr. Res. Rev. 2017;30:50–72. doi: 10.1017/S0954422416000238.
    1. Cunningham B.C., Mulkerrin M.G., Wells J.A. Dimerization of human growth hormone by zinc. Science. 1991;253:545–548. doi: 10.1126/science.1907025.
    1. Li R., Hui J., Luo G., Hong P., Li L., Yang Y., Zheng X., Lan H. Zinc ions increase GH signaling ability through regulation of available plasma membrane-localized GHR. J. Cell. Physiol. 2019;234:23388–23397. doi: 10.1002/jcp.28908.
    1. Petkovic V., Miletta M.C., Eblé A., Iliev D.I., Binder G., Flück C.E., Mullis P.E. Effect of zinc binding residues in growth hormone (GH) and altered intracellular zinc content on regulated GH secretion. Endocrinology. 2013;154:4215–4225. doi: 10.1210/en.2013-1089.
    1. Jacob R.S., Das S., Ghosh S., Anoop A., Jha N.N., Khan T., Singru P., Kumar A., Maji S.K. Amyloid formation of growth hormone in presence of zinc: Relevance to its storage in secretory granules. Sci. Rep. 2016;6 doi: 10.1038/srep23370.
    1. Balaz M., Ukropcova B., Kurdiova T., Gajdosechova L., Vlcek M., Janakova Z., Fedeles J., Pura M., Gasperikova D., Smith S.R., et al. Adipokine zinc-α2-glycoprotein regulated by growth hormone and linked to insulin sensitivity. Obesity. 2015;23:322–328. doi: 10.1002/oby.20856.
    1. MacDonald R.S. The role of zinc in growth and cell proliferation. J. Nutr. 2000;130:1500S–1508S. doi: 10.1093/jn/130.5.1500S.
    1. Roth H.P., Kirchgessner M. Influence of alimentary zinc deficiency on the concentration of growth hormone (GH), insulin-like growth factor I (IGF-I) and insulin in the serum of force-fed rats. Horm. Metab. Res. 1994;26:404–408. doi: 10.1055/s-2007-1001718.
    1. Ninh N.X., Thissen J.P., Maiter D., Adam E., Mulumba N., Ketelslegers J.M. Reduced liver insulin-like growth factor-I gene expression in young zinc-deprived rats is associated with a decrease in liver growth hormone (GH) receptors and serum GH-binding protein. J. Endocrinol. 1995;144:449–456. doi: 10.1677/joe.0.1440449.
    1. Hamza R.T., Hamed A.I., Sallam M.T. Effect of zinc supplementation on growth Hormone Insulin growth factor axis in short Egyptian children with zinc deficiency. Ital. J. Pediatr. 2012;38 doi: 10.1186/1824-7288-38-21.
    1. Ekbote V., Khadilkar A., Chiplonkar S., Mughal Z., Khadilkar V. Enhanced effect of zinc and calcium supplementation on bone status in growth hormone-deficient children treated with growth hormone: A pilot randomized controlled trial. Endocrine. 2013;43:686–695. doi: 10.1007/s12020-012-9847-0.
    1. de Medeiros Rocha É.D., de Brito N.J.N., Dantas M.M.G., de Araújo Silva A., das Graças Almeida M., Brandão-Neto J. Effect of Zinc Supplementation on GH, IGF1, IGFBP3, OCN, and ALP in Non-Zinc-Deficient Children. J. Am. Coll. Nutr. 2015;34:290–299. doi: 10.1080/07315724.2014.929511.
    1. Prodam F., Aimaretti G. Could zinc supplementation improve bone status in growth hormone (GH) deficient children? Endocrine. 2013;43:467–468. doi: 10.1007/s12020-013-9888-z.
    1. Bouglé D., Laroche D., Bureau F. Zinc and iron status and growth in healthy infants. Eur. J. Clin. Nutr. 2000;54:764–767. doi: 10.1038/sj.ejcn.1601087.
    1. Stred S.E., Messina J.L. Identification of hemopexin as a GH-regulated gene. Mol. Cell. Endocrinol. 2003;204:101–110. doi: 10.1016/S0303-7207(03)00149-7.
    1. Weinzimer S.A., Gibson T.B., Collett-Solberg P.F., Khare A., Liu B., Cohen P. Transferrin Is an Insulin-Like Growth Factor-Binding Protein-3 Binding Protein1. J. Clin. Endocrinol. Metab. 2001;86:1806–1813. doi: 10.1210/jcem.86.4.7380.
    1. Miyagawa S.I., Kobayashi M., Konishi N., Sato T., Ueda K. Insulin and insulin-like growth factor I support the proliferation of erythroid progenitor cells in bone marrow through the sharing of receptors. Br. J. Haematol. 2000;109:555–562. doi: 10.1046/j.1365-2141.2000.02047.x.
    1. Choi J., Kim S. Association of serum insulin-like growth factor-I and erythropoiesis in relation to body iron status. Ann. Clin. Lab. Sci. 2004;34:324–328.
    1. De Vita F., Maggio M., Lauretani F., Crucitti L., Bandinelli S., Mammarella F., Landi F., Ferrucci L., Ceda G.P. Insulin-like growth factor-1 and anemia in older subjects: The inchianti study. Endocr. Pract. 2015;21:1211–1218. doi: 10.4158/EP14100.OR.
    1. Vihervuori E., Cook J.D., Siimes M.A. Iron status of children with short stature during accelerated growth due to growth hormone treatment. Acta Paediatr. Int. J. Paediatr. 1997;86:588–593. doi: 10.1111/j.1651-2227.1997.tb08939.x.
    1. Anwar U., ZR A., Filteau S., Sullivan K., Tomkins A. The impact of maternal supplementation with a single dose of oral iodized poppyseed oil on infant thyroid status in rural Bangladesh. Trans. R. Soc. Trop. Med. Hyg. 1997;91:499–501.
    1. Zimmermann M.B., Jooste P.L., Mabapa N.S., Mbhenyane X., Schoeman S., Biebinger R., Chaouki N., Bozo M., Grimci L., Bridson J. Treatment of iodine deficiency in school-age children increases insulin-like growth factor (IGF)-I and IGF binding protein-3 concentrations and improves somatic growth. J. Clin. Endocrinol. Metab. 2007;92:437–442. doi: 10.1210/jc.2006-1901.
    1. Crew M., Spindler S. Thyroid hormone regulation of the transfected rat growth hormone promoter. J. Biol. Chem. 1986;261:5018–5022. doi: 10.1016/S0021-9258(19)89208-6.
    1. Miell J.P., Taylor A.M., Zini M., Maheshwari H.G., Ross R.J.M., Valcavi R. Effects of hypothyroidism and hyperthyroidism on insulin-like growth factors (IGFs) and growth hormone- and IGF-binding proteins. J. Clin. Endocrinol. Metab. 1993;76:950–955. doi: 10.1210/jcem.76.4.7682563.
    1. Nanto-Salonen K., Muller H.L., Hoffman A.R., Vu T.H., Rosenfeld R.G. Mechanisms of thyroid hormone action on the insulinlike growth factor system: All thyroid hormone effects are not growth hormone mediated. Endocrinology. 1993;132:781–788. doi: 10.1210/endo.132.2.7678799.
    1. Thorlacius-Ussing O., Flyvbjerg A., Esmann J. Evidence that selenium induces growth retardation through reduced growth hormone and somatomedin c production. Endocrinology. 1987;120:659–663. doi: 10.1210/endo-120-2-659.
    1. Rayman M.P. The importance of selenium to human health. Lancet. 2000;356:233–241. doi: 10.1016/S0140-6736(00)02490-9.
    1. Ren G., Ali T., Chen W., Han D., Zhang L., Gu X., Zhang S., Ding L., Fanning S., Han B. The role of selenium in insulin-like growth factor I receptor (IGF-IR) expression and regulation of apoptosis in mouse osteoblasts. Chemosphere. 2016;144:2158–2164. doi: 10.1016/j.chemosphere.2015.11.003.
    1. Wang J., Lian S., He X., Yu D., Liang J., Sun D., Wu R. Selenium deficiency induces splenic growth retardation by deactivating the IGF-1R/PI3K/Akt/mTOR pathway. Metallomics. 2018;10:1570–1575. doi: 10.1039/C8MT00183A.
    1. Moreno-Reyes R., Egrise D., Nève J., Pasteels J.L., Schoutens A. Selenium deficiency-induced growth retardation is associated with an impaired bone metabolism and osteopenia. J. Bone Miner. Res. 2001;16:1556–1563. doi: 10.1359/jbmr.2001.16.8.1556.
    1. Maggio M., De Vita F.D., Lauretani F., Buttò V., Bondi G., Cattabiani C., Nouvenne A., Meschi T., Dall’Agli E., Ceda G.P. IGF-1, the cross road of the nutritional, inflammatory and hormonal pathways to frailty. Nutrients. 2013;5:4184–4205. doi: 10.3390/nu5104184.
    1. Aydin K., Bideci A., Kendirci M., Cinaz P., Kurtoglu S. Insulin-like growth factor-I and insulin-like growth factor binding protein-3 levels of children living in an iodine- and selenium-deficient endemic goiter area. Biol. Trace Elem. Res. 2002;90:25–30. doi: 10.1385/BTER:90:1-3:25.
    1. Maggio M., Ceda G.P., Lauretani F., Bandinelli S., Dall’Aglio E., Guralnik J.M., Paolisso G., Semba R.D., Nouvenne A., Borghi L., et al. Association of plasma selenium concentrations with total IGF-1 among older community-dwelling adults: The InCHIANTI study. Clin. Nutr. 2010;29:674–677. doi: 10.1016/j.clnu.2010.03.012.
    1. Young N.J., Metcalfe C., Gunnell D., Rowlands M.A., Lane J.A., Gilbert R., Avery K.N.L., Davis M., Neal D.E., Hamdy F.C., et al. A cross-sectional analysis of the association between diet and insulin-like growth factor (IGF)-I, IGF-II, IGF-binding protein (IGFBP)-2, and IGFBP-3 in men in the United Kingdom. Cancer Causes Control. 2012;23:907–917. doi: 10.1007/s10552-012-9961-6.
    1. Janjuha R., Bunn D., Hayhoe R., Hooper L., Abdelhamid A., Mahmood S., Hayden-Case J., Appleyard W., Morris S., Welch A. Effects of dietary or supplementary micronutrients on sex hormones and IGF-1 in middle and older age: A systematic review and meta-analysis. Nutrients. 2020;12:1457. doi: 10.3390/nu12051457.
    1. Werner L., Korc M., Brannon P.M. Effects of manganese deficiency and dietary composition on rat pancreatic enzyme content. J. Nutr. 1987;117:2079–2085. doi: 10.1093/jn/117.12.2079.
    1. Clegg M.S., Donovan S.M., Monaco M.H., Baly D.L., Ensunsa J.L., Keen C.L. The influence of manganese deficiency on serum IGF-1 and IGF binding proteins in the male rat. Proc. Soc. Exp. Biol. Med. 1998;219:41–47. doi: 10.3181/00379727-219-44314.
    1. Bryan M.R., Nordham K.D., Rose D.I.R., O’Brien M.T., Joshi P., Foshage A.M., Gonçalves F.M., Nitin R., Uhouse M.A., Aschner M., et al. Manganese Acts upon Insulin/IGF Receptors to Phosphorylate AKT and Increase Glucose Uptake in Huntington’s Disease Cells. Mol. Neurobiol. 2020;57:1570–1593. doi: 10.1007/s12035-019-01824-1.
    1. Hiney J.K., Srivastava V.K., Dees W. Les Manganese induces IGF-1 and cyclooxygenase-2 gene expressions in the basal hypothalamus during prepubertal female development. Toxicol. Sci. 2011;121:389–396. doi: 10.1093/toxsci/kfr057.
    1. Yang W., Wang J., Zhu X., Gao Y., Liu Z., Zhang L., Chen H., Shi X., Yang L., Liu G. High lever dietary copper promote ghrelin gene expression in the fundic gland of growing pigs. Biol. Trace Elem. Res. 2012;150:154–157. doi: 10.1007/s12011-012-9477-7.
    1. Roughead Z.K.F., Lukaski H.C. Inadequate copper intake reduces serum insulin-like growth factor-I and bone strength in growing rats fed graded amounts of copper and zinc. J. Nutr. 2003;33:442–448. doi: 10.1093/jn/133.2.442.
    1. Yang W., Wang J., Liu L., Zhu X., Wang X., Liu Z., Wang Z., Yang L., Liu G. Effect of high dietary copper on somatostatin and growth hormone-releasing hormone levels in the hypothalami of growing pigs. Biol. Trace Elem. Res. 2011;143:893–900. doi: 10.1007/s12011-010-8904-x.
    1. Wang M.Q., Xu Z.R., Li W.F., Jiang Z.G. Effect of chromium nanocomposite supplementation on growth hormone pulsatile secretion and mRNA expression in finishing pigs. J. Anim. Physiol. Anim. Nutr. 2009;93:520–525. doi: 10.1111/j.1439-0396.2008.00836.x.
    1. Merimee T.J., Pulkkinen A.J., Burton C.E. Diet-induced alterations of hgh secretion in man. J. Clin. Endocrinol. Metab. 1976;42:931–937. doi: 10.1210/jcem-42-5-931.
    1. Harber M.P., Schenk S., Barkan A.L., Horowitz J.F. Effects of dietary carbohydrate restriction with high protein intake on protein metabolism and the somatotropic axis. J. Clin. Endocrinol. Metab. 2005;90:5175–5181. doi: 10.1210/jc.2005-0559.
    1. McCargar L.J., Clandinin M.T., Belcastro A.N., Walker K. Dietary carbohydrate-to-fat ratio: Influence on whole-body nitrogen retention, substrate utilization, and hormone response in healthy male subjects. Am. J. Clin. Nutr. 1989;49:1169–1178. doi: 10.1093/ajcn/49.6.1169.
    1. Darling-Raedeke M., Thornton W.H., MacDonald R.S. Growth hormone and igf-i plasma concentrations and macronutrient intake measured in a free-living elderly population during a one-year period. J. Am. Coll. Nutr. 1998;17:392–397. doi: 10.1080/07315724.1998.10718782.
    1. Fontana L., Partridge L., Longo V.D. Extending healthy life span-from yeast to humans. Science. 2010;328:321–326. doi: 10.1126/science.1172539.
    1. López-Otín C., Blasco M.A., Partridge L., Serrano M., Kroemer G. The hallmarks of aging. Cell. 2013;153:1194. doi: 10.1016/j.cell.2013.05.039.
    1. Holloszy J.O., Fontana L. Caloric restriction in humans. Exp. Gerontol. 2007;42:709–712. doi: 10.1016/j.exger.2007.03.009.
    1. Efeyan A., Comb W.C., Sabatini D.M. Nutrient-sensing mechanisms and pathways. Nature. 2015;517:302–310. doi: 10.1038/nature14190.
    1. Redman L.M., Smith S.R., Burton J.H., Martin C.K., Il’yasova D., Ravussin E. Metabolic Slowing and Reduced Oxidative Damage with Sustained Caloric Restriction Support the Rate of Living and Oxidative Damage Theories of Aging. Cell Metab. 2018;27:805–815.e4. doi: 10.1016/j.cmet.2018.02.019.
    1. Fontana L., Klein S. Aging, adiposity, and calorie restriction. J. Am. Med. Assoc. 2007;297:986–994. doi: 10.1001/jama.297.9.986.
    1. Mercken E.M., Crosby S.D., Lamming D.W., Jebailey L., Krzysik-Walker S., Villareal D.T., Capri M., Franceschi C., Zhang Y., Becker K., et al. Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile. Aging Cell. 2013;12:645–651. doi: 10.1111/acel.12088.
    1. Milman S., Atzmon G., Huffman D.M., Wan J., Crandall J.P., Cohen P., Barzilai N. Low insulin-like growth factor-1 level predicts survival in humans with exceptional longevity. Aging Cell. 2014;13:769–771. doi: 10.1111/acel.12213.
    1. Renehan A.G., Zwahlen M., Minder C., O’Dwyer S.T., Shalet S.M., Egger M. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: Systematic review and meta-regression analysis. Lancet. 2004;363:1346–1353. doi: 10.1016/S0140-6736(04)16044-3.
    1. Bartke A. Pleiotropic effects of growth hormone signaling in aging. Trends Endocrinol. Metab. 2011;22:437–442. doi: 10.1016/j.tem.2011.07.004.
    1. Al-Regaiey K.A., Masternak M.M., Bonkowski M., Sun L., Bartke A. Long-lived growth hormone receptor knockout mice: Interaction of reduced insulin-like growth factor I/insulin signaling and caloric restriction. Endocrinology. 2005;146:851–860. doi: 10.1210/en.2004-1120.
    1. Bartke A. Role of the growth hormone/insulin-like growth factor system in mammalian aging. Endocrinology. 2005;146:3718–3723. doi: 10.1210/en.2005-0411.
    1. Longo V.D., Fontana L. Calorie restriction and cancer prevention: Metabolic and molecular mechanisms. Trends Pharmacol. Sci. 2010;31:89–98. doi: 10.1016/j.tips.2009.11.004.
    1. Sabatino F., Masoro E.J., McMahan C.A., Kuhn R.W. Assessment of the role of the glucocorticoid system in aging processes and in the action of food restriction. J. Gerontol. 1991;46 doi: 10.1093/geronj/46.5.B171.
    1. Redman L.M., Veldhuis J.D., Rood J., Smith S.R., Williamson D., Ravussin E. The effect of caloric restriction interventions on growth hormone secretion in nonobese men and women. Aging Cell. 2010;9:32–39. doi: 10.1111/j.1474-9726.2009.00530.x.
    1. Cohen D.E., Supinski A.M., Bonkowski M.S., Donmez G., Guarente L.P. Neuronal SIRT1 regulates endocrine and behavioral responses to calorie restriction. Genes Dev. 2009;23:2812–2817. doi: 10.1101/gad.1839209.
    1. Sonntag W.E., Xu X., Ingram R.L., D’Costa A. Moderate caloric restriction alters the subcellular distribution of somatostatin mRNA and increases growth hormone pulse amplitude in aged animals. Neuroendocrinology. 1995;61:601–608. doi: 10.1159/000126885.
    1. Caputo M., Mele C., Ferrero A., Leone I., Daffara T., Marzullo P., Prodam F., Aimaretti G. Dynamic tests in pituitary endocrinology: Pitfalls in interpretation during aging. Neuroendocrinology. 2021 doi: 10.1159/000514434.
    1. Bartke A., Wright J.C., Mattison J.A., Ingram D.K., Miller R.A., Roth G.S. Extending the lifespan of long-lived mice. Nature. 2001;414:412. doi: 10.1038/35106646.
    1. Dani S.U., Dani M.A.C., Freire I.L., Gouvea S.P., Knackfuss F.B., Lima F.P., Mercadante M.E.Z., Monteiro E., Paggiaro S.M.G., Razook A.G., et al. Survival of the thriftiest: Restricted nurture reveals the thrifty nature of a growth gene in Bos indicus. Genet. Mol. Res. 2010;9:1032–1044. doi: 10.4238/vol9-2gmr844.
    1. Sonntag W.E., Csiszar A., De Cabo R., Ferrucci L., Ungvari Z. Diverse roles of growth hormone and insulin-like growth factor-1 in mammalian aging: Progress and controversies. J. Gerontol. Ser. A Biol. Sci. Med. Sci. 2012;67:587–598. doi: 10.1093/gerona/gls115.
    1. Suh Y., Atzmon G., Cho M.O., Hwang D., Liu B., Leahy D.J., Barzilai N., Cohen P. Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc. Natl. Acad. Sci. USA. 2008;105:3438–3442. doi: 10.1073/pnas.0705467105.
    1. Guevara-Aguirre J., Balasubramanian P., Guevara-Aguirre M., Wei M., Madia F., Cheng C.W., Hwang D., Martin-Montalvo A., Saavedra J., Ingles S., et al. Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Sci. Transl. Med. 2011;3 doi: 10.1126/scitranslmed.3001845.
    1. Fontana L., Weiss E.P., Villareal D.T., Klein S., Holloszy J.O. Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell. 2008;7:681–687. doi: 10.1111/j.1474-9726.2008.00417.x.
    1. Gavrilova N.S., Gavrilov L.A. Comments on dietary restriction, okinawa diet and longevity. Gerontology. 2012;58:221–223. doi: 10.1159/000329894.
    1. Willcox D.C., Willcox B.J., Todoriki H., Curb J.D., Suzuki M. Caloric restriction and human longevity: What can we learn from the Okinawans? Biogerontology. 2006;7:173–177. doi: 10.1007/s10522-006-9008-z.
    1. Willcox D., Willcox B., Yasura S., Ashitomi I., Suzuki M. Gender gap in healthspan and life expectancy in Okinawa: Health behaviours. Asian J. Gerontol. Geriatr. 2012;7:49.
    1. Lynch C.J., Adams S.H. Branched-chain amino acids in metabolic signalling and insulin resistance. Nat. Rev. Endocrinol. 2014;10:723–736. doi: 10.1038/nrendo.2014.171.
    1. Catenacci V.A., Pan Z., Ostendorf D., Brannon S., Gozansky W.S., Mattson M.P., Martin B., MacLean P.S., Melanson E.L., Troy Donahoo W. A randomized pilot study comparing zero-calorie alternate-day fasting to daily caloric restriction in adults with obesity. Obesity. 2016;24:1874–1883. doi: 10.1002/oby.21581.
    1. Varady K.A., Bhutani S., Church E.C., Klempel M.C. Short-term modified alternate-day fasting: A novel dietary strategy for weight loss and cardioprotection in obese adults. Am. J. Clin. Nutr. 2009;90:1138–1143. doi: 10.3945/ajcn.2009.28380.
    1. Harvie M., Wright C., Pegington M., McMullan D., Mitchell E., Martin B., Cutler R.G., Evans G., Whiteside S., Maudsley S., et al. The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women. Br. J. Nutr. 2013;110:1534–1547. doi: 10.1017/S0007114513000792.
    1. Varady K.A., Bhutani S., Klempel M.C., Kroeger C.M., Trepanowski J.F., Haus J.M., Hoddy K.K., Calvo Y. Alternate day fasting for weight loss in normal weight and overweight subjects: A randomized controlled trial. Nutr. J. 2013;12 doi: 10.1186/1475-2891-12-146.
    1. Varady K.A., Roohk D.J., Loe Y.C., McEvoy-Hein B.K., Hellerstein M.K. Effects of modified alternate-day fasting regimens on adipocyte size, triglyceride metabolism, and plasma adiponectin levels in mice. J. Lipid Res. 2007;48:2212–2219. doi: 10.1194/jlr.M700223-JLR200.
    1. Varady K.A., Allister C.A., Roohk D.J., Hellerstein M.K. Improvements in body fat distribution and circulating adiponectin by alternate-day fasting versus calorie restriction. J. Nutr. Biochem. 2010;21:188–195. doi: 10.1016/j.jnutbio.2008.11.001.
    1. Varady K.A., Hudak C.S., Hellerstein M.K. Modified alternate-day fasting and cardioprotection: Relation to adipose tissue dynamics and dietary fat intake. Metabolism. 2009;58:803–811. doi: 10.1016/j.metabol.2009.01.018.
    1. Ash S., Reeves M.M., Yeo S., Morrison G., Carey D., Capra S. Effect of intensive dietetic interventions on weight and glycaemic control in overweight men with Type II diabetes: A randomised trial. Int. J. Obes. 2003;27:797–802. doi: 10.1038/sj.ijo.0802295.
    1. Klempel M.C., Kroeger C.M., Bhutani S., Trepanowski J.F., Varady K.A. Intermittent fasting combined with calorie restriction is effective for weight loss and cardio-protection in obese women. Nutr. J. 2012;11 doi: 10.1186/1475-2891-11-98.
    1. Hoddy K.K., Kroeger C.M., Trepanowski J.F., Barnosky A., Bhutani S., Varady K.A. Meal timing during alternate day fasting: Impact on body weight and cardiovascular disease risk in obese adults. Obesity. 2014;22:2524–2531. doi: 10.1002/oby.20909.
    1. Eshghinia S., Mohammadzadeh F. The effects of modified alternate-day fasting diet on weight loss and CAD risk factors in overweight and obese women. J. Diabetes Metab. Disord. 2013;12 doi: 10.1186/2251-6581-12-4.
    1. Zuo L., He F., Tinsley G.M., Pannell B.K., Ward E., Arciero P.J. Comparison of high-protein, intermittent fasting low-calorie diet and heart healthy diet for vascular health of the obese. Front. Physiol. 2016;7 doi: 10.3389/fphys.2016.00350.
    1. Harvie M.N., Sims A.H., Pegington M., Spence K., Mitchell A., Vaughan A.A., Allwood J.W., Xu Y., Rattray N.J.W., Goodacre R., et al. Intermittent energy restriction induces changes in breast gene expression and systemic metabolism. Breast Cancer Res. 2016;18 doi: 10.1186/s13058-016-0714-4.
    1. Wegman M.P., Guo M.H., Bennion D.M., Shankar M.N., Chrzanowski S.M., Goldberg L.A., Xu J., Williams T.A., Lu X., Hsu S.I., et al. Practicality of Intermittent Fasting in Humans and its Effect on Oxidative Stress and Genes Related to Aging and Metabolism. Rejuvenation Res. 2015;18:162–172. doi: 10.1089/rej.2014.1624.
    1. Ułamek-Kozioł M., Czuczwar S.J., Pluta R., Januszewski S. Ketogenic diet and epilepsy. Nutrients. 2019;11:2510. doi: 10.3390/nu11102510.
    1. Caprio M., Infante M., Moriconi E., Armani A., Fabbri A., Mantovani G., Mariani S., Lubrano C., Poggiogalle E., Migliaccio S., et al. Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: Systematic review and consensus statement from the Italian Society of Endocrinology (SIE) J. Endocrinol. Investig. 2019;42:1365–1386. doi: 10.1007/s40618-019-01061-2.
    1. Coopmans E.C., Berk K.A.C., El-Sayed N., Neggers S.J.C.M.M., van der Lely A.J. Eucaloric Very-Low-Carbohydrate Ketogenic Diet in Acromegaly Treatment. N. Engl. J. Med. 2020;382:2161–2162. doi: 10.1056/NEJMc1915808.
    1. Kossoff E.H., Zupec-Kania B.A., Auvin S., Ballaban-Gil K.R., Christina Bergqvist A.G., Blackford R., Buchhalter J.R., Caraballo R.H., Cross J.H., Dahlin M.G., et al. Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open. 2018;3:175–192. doi: 10.1002/epi4.12225.
    1. Peterson S.J., Tangney C.C., Pimentel-Zablah E.M., Hjelmgren B., Booth G., Berry-Kravis E. Changes in growth and seizure reduction in children on the ketogenic diet as a treatment for intractable epilepsy. J. Am. Diet. Assoc. 2005;105:718–724. doi: 10.1016/j.jada.2005.02.009.
    1. Spulber G., Spulber S., Hagenäs L., Åmark P., Dahlin M. Growth dependence on insulin-like growth factor-1 during the ketogenic diet. Epilepsia. 2009;50:297–303. doi: 10.1111/j.1528-1167.2008.01769.x.
    1. Vining E.P.G., Pyzik P., McGrogan J., Hladky H., Anand A., Kriegler S., Freeman J.M. Growth of children on the ketogenic diet. Dev. Med. Child Neurol. 2002;44:796–802. doi: 10.1111/j.1469-8749.2002.tb00769.x.
    1. Wiĺliams S., Basualdo-Hammond C., Curtis R., Schuller R. Growth retardation in children with epilepsy on the ketogenic diet: A retrospective chart review. J. Am. Diet. Assoc. 2002;102:405–407. doi: 10.1016/S0002-8223(02)90093-3.
    1. Groleau V., Schall J.I., Stallings V.A., Bergqvist C.A. Long-term impact of the ketogenic diet on growth and resting energy expenditure in children with intractable epilepsy. Dev. Med. Child Neurol. 2014;56:898–904. doi: 10.1111/dmcn.12462.
    1. Kim J.T., Kang H.C., Song J.E., Lee M.J., Lee Y.J., Lee E.J., Lee J.S., Kim H.D. Catch-up growth after long-term implementation and weaning from ketogenic diet in pediatric epileptic patients. Clin. Nutr. 2013;32:98–103. doi: 10.1016/j.clnu.2012.05.019.
    1. Marchiò M., Roli L., Lucchi C., Costa A.M., Borghi M., Iughetti L., Trenti T., Guerra A., Biagini G. Ghrelin Plasma Levels After 1 Year of Ketogenic Diet in Children With Refractory Epilepsy. Front. Nutr. 2019;6 doi: 10.3389/fnut.2019.00112.
    1. Wibisono C., Rowe N., Beavis E., Kepreotes H., Mackie F.E., Lawson J.A., Cardamone M. Ten-year single-center experience of the ketogenic diet: Factors influencing efficacy, tolerability, and compliance. J. Pediatr. 2015;166:1030–1036.e1. doi: 10.1016/j.jpeds.2014.12.018.
    1. Lambrechts D.A.J.E., de Kinderen R.J.A., Vles H.S.H., de Louw A.J., Aldenkamp A.P., Majoie M.J.M. The MCT-ketogenic diet as a treatment option in refractory childhood epilepsy: A prospective study with 2-year follow-up. Epilepsy Behav. 2015;51:261–266. doi: 10.1016/j.yebeh.2015.07.023.
    1. Dressler A., Stöcklin B., Reithofer E., Benninger F., Freilinger M., Hauser E., Reiter-Fink E., Seidl R., Trimmel-Schwahofer P., Feucht M. Long-term outcome and tolerability of the ketogenic diet in drug-resistant childhood epilepsy-the austrian experience. Seizure. 2010;19:404–408. doi: 10.1016/j.seizure.2010.06.006.
    1. Ferraris C., Guglielmetti M., Pasca L., De Giorgis V., Ferraro O.E., Brambilla I., Leone A., De Amicis R., Bertoli S., Veggiotti P., et al. Impact of the ketogenic diet on linear growth in children: A single-center retrospective analysis of 34 cases. Nutrients. 2019;11:1442. doi: 10.3390/nu11071442.
    1. Armeno M., Verini A., del Pino M., Araujo M.B., Mestre G., Reyes G., Caraballo R.H. A prospective study on changes in nutritional status and growth following two years of ketogenic diet (KD) therapy in children with refractory epilepsy. Nutrients. 2019;11:1596. doi: 10.3390/nu11071596.
    1. Nation J., Humphrey M., Mackay M., Boneh A. Linear growth of children on a ketogenic diet: Does the protein-to-energy ratio matter? J. Child Neurol. 2014;29:1496–1501. doi: 10.1177/0883073813508222.
    1. Svedlund A., Hallböök T., Magnusson P., Dahlgren J., Swolin-Eide D. Prospective study of growth and bone mass in Swedish children treated with the modified Atkins diet. Eur. J. Paediatr. Neurol. 2019;23:629–638. doi: 10.1016/j.ejpn.2019.04.001.
    1. Salas-Salvadó J., Fernández-Ballart J., Ros E., Martínez-González M.A., Fitó M., Estruch R., Corella D., Fiol M., Gómez-Gracia E., Arós F., et al. Effect of a Mediterranean diet supplemented with nuts on metabolic syndrome status: One-year results of the PREDIMED randomized trial. Arch. Intern. Med. 2008;168:2449–2458. doi: 10.1001/archinte.168.22.2449.
    1. Muscogiuri G., Barrea L., Laudisio D., Di Somma C., Pugliese G., Salzano C., Colao A., Savastano S. Somatotropic axis and obesity: Is there any role for the Mediterranean diet? Nutrients. 2019;11:2228. doi: 10.3390/nu11092228.
    1. Vila G., Jørgensen J.O.L., Luger A., Stalla G.K. Insulin resistance in patients with acromegaly. Front. Endocrinol. 2019;10:509. doi: 10.3389/fendo.2019.00509.
    1. Jørgensen J.O.L. Treatment guidelines for acromegaly. Report from a Scandinavian workshop. Growth Horm. IGF Res. 2001;11:72–74.
    1. Widmer R.J., Flammer A.J., Lerman L.O., Lerman A. The Mediterranean diet, its components, and cardiovascular disease. Am. J. Med. 2015;128:229–238. doi: 10.1016/j.amjmed.2014.10.014.
    1. Whitehead T., Robinson D., Allaway S., Syms J., Hale A. Effect of red wine ingestion on the antioxidant capacity of serum. Clin. Chem. 1995;41:32–35. doi: 10.1093/clinchem/41.1.32.
    1. Lasheras C., Gonzalez S., Huerta J.M., Lombardia C., Ibañez R., Patterson A.M., Fernandez S. Food habits are associated with lipid peroxidation in an elderly population. J. Am. Diet. Assoc. 2003;103:1480–1487. doi: 10.1016/j.jada.2003.08.023.
    1. Antonini F.M., Petruzzi E., Pinzani P., Orlando C., Petruzzi I., Pazzagli M., Masotti G. Effect of diet and red wine consumption on serum total antioxidant capacity (TAC), dehydroepiandrosterone-sulphate (DHEAS) and insulin-like growth factor-1 (IGF-1) in Italian centenarians. Arch. Gerontol. Geriatr. 2005;41:151–157. doi: 10.1016/j.archger.2005.01.003.
    1. Sambrook P.N., Chen J.S., March L.M., Cameron I.D., Cumming R.G., Lord S.R., Zochling J., Sitoh Y.Y., Lau T.C., Schwarz J., et al. Serum parathyroid hormone predicts time to fall independent of vitamin D status in a frail elderly population. J. Clin. Endocrinol. Metab. 2004;89:1572–1576. doi: 10.1210/jc.2003-031782.
    1. Bassaganya-Riera J., Berry E.M., Blaak E.E., Burlingame B., le Coutre J., van Eden W., El-Sohemy A., German J.B., Knorr D., Lacroix C., et al. Goals in Nutrition Science 2020–2025. Front. Nutr. 2021;7:606378. doi: 10.3389/fnut.2020.606378.
    1. Solon-Biet S.M., Mitchell S.J., de Cabo R., Raubenheimer D., Le Couteur D.G., Simpson S.J. Macronutrients and caloric intake in health and longevity. J. Endocrinol. 2015;226:R17–R28. doi: 10.1530/JOE-15-0173.
    1. Johnson S.C. Subcellular Biochemistry. Volume 90. Springer; New York, NY, USA: 2018. Nutrient sensing, signaling and ageing: The role of IGF-1 and mTOR in ageing and age-related disease; pp. 49–97.
    1. Brown-Borg H.M. The somatotropic axis and longevity in mice. Am. J. Physiol. Endocrinol. Metab. 2015;309:E503–E510. doi: 10.1152/ajpendo.00262.2015.
    1. Simpson S.J., Raubenheimer D. Caloric restriction and aging revisited: The need for a geometric analysis of the nutritional bases of aging. J. Gerontol. Ser. A Biol. Sci. Med. Sci. 2007;62:707–713. doi: 10.1093/gerona/62.7.707.
    1. Simpson S., Raubenheimer D. The Nature of Nutrition. A Unifying Framework Form Animal Adaption to Human Obesity. Princeton University Press; Princeton, NJ, USA: 2012.

Source: PubMed

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