Exercise increases serum fibroblast growth factor 21 (FGF21) levels

Daniel Cuevas-Ramos, Paloma Almeda-Valdés, Clara Elena Meza-Arana, Griselda Brito-Córdova, Francisco J Gómez-Pérez, Roopa Mehta, Jorge Oseguera-Moguel, Carlos A Aguilar-Salinas, Daniel Cuevas-Ramos, Paloma Almeda-Valdés, Clara Elena Meza-Arana, Griselda Brito-Córdova, Francisco J Gómez-Pérez, Roopa Mehta, Jorge Oseguera-Moguel, Carlos A Aguilar-Salinas

Abstract

Background: Fibroblast growth factor 21 (FGF21) increases glucose uptake. It is unknown if FGF21 serum levels are affected by exercise.

Methodology/principal findings: This was a comparative longitudinal study. Anthropometric and biochemical evaluation were carried out before and after a bout of exercise and repeated after two weeks of daily supervised exercise. The study sample was composed of 60 sedentary young healthy women. The mean age was 24±3.7 years old, and the mean BMI was 21.4±7.0 kg/m². The anthropometric characteristics did not change after two weeks of exercise. FGF21 levels significantly increased after two weeks of exercise (276.8 ng/l (142.8-568.6) vs. (460.8 (298.2-742.1), p<0.0001)). The delta (final-basal) log of serum FGF21, adjusted for BMI, showed a significant positive correlation with basal glucose (r = 0.23, p = 0.04), mean maximal heart rate (MHR) (r = 0.54, p<0.0001), mean METs (r = 0.40, p = 0.002), delta plasma epinephrine (r = 0.53, p<0.0001) and delta plasma FFAs (r = 0.35, p = 0.006). A stepwise linear regression model showed that glucose, MHR, METs, FFAs, and epinephrine, were factors independently associated with the increment in FGF21 after the exercise program (F = 4.32; r² = 0.64, p<0.0001).

Conclusions: Serum FGF21 levels significantly increased after two weeks of physical activity. This increment correlated positively with clinical parameters related to the adrenergic and lipolytic response to exercise.

Trial registration: ClinicalTrials.gov NCT01512368.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Flow chart of the study…
Figure 1. Flow chart of the study protocol.
Figure 2. Correlation of the log delta…
Figure 2. Correlation of the log delta FGF21 (final-basal) levels with METs (A), delta epinephrine (B), and delta free fatty acids (C) in 60 women after two weeks of supervised physical activity.

References

    1. Kharitonenkov A, Shiyanova TL, Koester A, Ford AM, Micanovic R, et al. FGF-21 as a novel metabolic regulator. J Clin Invest. 2005;115:1627–1635.
    1. Nishimura T, Nakatake Y, Konishi M, Itoh N. Identification of a novel FGF, FGF-21, preferentially expressed in the liver. Biochim Biophys Acta. 2000;1492:203–206.
    1. Gälman C, Lundasen T, Kharinonekov A, Eriksson M, Haström I, et al. The circulating metabolic regulator FGF21 is induced by prolonged fasting and PPAR-α activation in man. Cell Metab. 2008;8:169–74.
    1. Potthoff MJ, Inagaki T, Satapati S, Ding X, He T, et al. FGF21 induces PGC-1alfa and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response. Proce Natl Acad Sci. 2009;106:10853–10858.
    1. Coskun T, Bina HA, Schneider MA, Dunbar JD, Hu CC, et al. Fibroblast growth factor 21 corrects obesity in mice. Endocrinology. 2008;149:6018–6027.
    1. Kliewer SA, Mangelsdorf DJ. Fibroblast growth factor 21: from pharmacology to physiology. Am J Clin Nutr. 2010;91:254S–257S.
    1. Hojman P, Pedersen M, Nielsen RA, Krogh-Madsen R, Yfanti Ch, et al. Fibroblast growth factor-21 is induced in human skeletal muscles by hyperinsulinemia. Diabetes. 2009;58:2797–2801.
    1. Zhang X, Yeung DC, Karpisek M, Stejskal D, Zhou ZG, et al. Serum FGF21 levels are increased in obesity and are independently associated with the Metabolic Syndrome in Humans. Diabetes. 2008;57:1246–53.
    1. Cuevas-Ramos D, Almeda-Valdés P, Gómez-Pérez FJ, Meza-Arana CE, Cruz-Bautista I, et al. Daily physical activity, fasting glucose, uric acid, and body mass index are independent factors associated with serum fibroblast growth factor 21 levels. Eur J Endocrinol. 2010;163:469–477.
    1. Horton TJ, Dow S, Armstrong M, Donahoo WT. Grater systemic lipolysis in women compared with men during moderate-dose infusion of epinephrine and/or norepinephrine. J Appl Physiol. 2009;107:200–210.
    1. Tremblay MS, Colley RC, Saunders TJ. Physiological and health implications of a sedentary lifestyle. Appl Physiol Nutr Metab. 2010;35:725–740.
    1. Hill J, Timmis A. Exercise tolerance testing. Brit Med J. 2002;324:1084–1087.
    1. López-Alvarenga JC, Reyes-Díaz S, Castillo-Martínez L, Dávalos-Ibáñez A, González-Barranco J. Reproducibilidad y sensibilidad de un cuestionario de actividad física en población mexicana. Salud Pública de México. 2001;43:306–312.
    1. Mai K, Andres J, Biedasek K, Weicht J, Bobbert T, et al. Free fatty acids link metabolism and regulation of the insulin-sensitizing fibroblast growth factor 21. Diabetes 58; 2009;1532–1538
    1. Henderson GC, Fattor JA, Horning MA, Faghihnia N, Johnson ML, et al. Lypolysis and fatty acid metabolism in men and women during postexercise recovery period. J Physiol. 2007;584.3:963–981.
    1. Hom GJ, Forrest MJ, Bach TJ, Brady E, Candelore MR, et al. Beta 3-adrenoreceptor agonist-induced increases in lypolysis, metabolic rate, facial flushing, and reflex tachycardia in anesthetized rhesus monkeys. J Pharmacol Exp Ther 297; 2001;299–307
    1. de Glisezinski I, Larrouy D, Bajzova M, Koppo K, Polak J, et al. Adrenaline but not noradrenaline is a determinant of exercise-induced lipid mobilization in human subcutaneous adipose tissue. J Physiol. 2009;587:3393–3404.
    1. Wahrenberg H, Bolinder J, Arner P. Adrenergic regulation of lipolysis in human fat cells during exercise. Eur J Clin Invest. 1991;21:534–541.
    1. Badman MK, Pissios P, Kennedy AR, Koukos G, Flier JS, et al. Hepatic fibroblast growth factor 21 is regulated by PPAR-alfa and is a key mediator of hepatic lipid metabolism in ketotic states. Cell Metab. 2007;5:426–437.
    1. Inagaki T, Dutchak P, Zhao G, Ding X, Gautron L, et al. Endocrine regulation of the fasting response by PPAR-alfa-mediated induction of FGF21. Cell Metab. 2007;5:415–425.
    1. Lundasen T, Hunt MC, Nilsson LM, Sanyal S, Angelin B, et al. PPARalfa is a key regulator of hepatic FGF21. Biochemical and Biophysical Research Communications 360; 2007;437–440
    1. Uebanso T, Taketani Y, Yamamoto H, Amo K, Ominami H, et al. Paradoxical regulation of human FGF21 by both fasting and feeding signals: is FGF21 a nutritional adaptation factor? PLoS ONE 6; 2011;e22976
    1. Schoenberg KM, Giesy SL, Harvatine KJ, Waldron MR, Cheng C, et al. Plasma FGF21 Is Elevated by the Intense Lipid Mobilization of Lactation. Endocrinology. 2011;152:4652–4561.
    1. Chen W, Hoo RL, Konishi M, Itoh N, Lee PC, et al. Growth hormone induces hepatic production of fibroblast growth factor 21 through a mechanism dependent on lipolysis in adipocytes. J Biol Chem. 2011;286:34559–34566.
    1. Yan H, Xia M, Chang X, Xu Q, Bian H, et al. Circulating fibroblast growth factor 21 levels are closely associated with hepatic fat content: A cross-sectional study. PLoS ONE. 2011;6:e24895.
    1. Chavez AO, Molina-Carrion M, Abdul-Ghani MA, Folli F, DeFronzo RA, et al. Circulating fibroblast growth factor-21 is elevated in impaired glucose tolerance and type 2 diabetes and correlates with muscle and hepatic insulin resistance. Diabetes Care. 2009;32:1542–1546.
    1. Lund S, Holman GD, Schmitz O, Pedersen O. Contraction stimulates translocation of glucose transporter GLUT4 in skeletal muscle through a mechanism distinct from that of insulin. Proc Natl Acad Sci USA 92; 1995;5817–5821
    1. Arner P, Pettersson A, Mitchell PJ, Dunbar JD, Kharitonenkov A, et al. FGF21 attenuates lipolysis in human adipocytes: a possible link to improved insulin sensitivity. FEBS Lett. 2008;582:1725–1730.
    1. Li L, Pan R, Li R, Niemann B, Aurich AC, et al. Mitochondrial biogenesis and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC1alfa) deacetylation by physical activity. Diabetes 60; 2011;157–167

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa