Novel insight into perirenal adipose tissue: A neglected adipose depot linking cardiovascular and chronic kidney disease

Na Huang, En-Wen Mao, Ning-Ning Hou, Yong-Ping Liu, Fang Han, Xiao-Dong Sun, Na Huang, En-Wen Mao, Ning-Ning Hou, Yong-Ping Liu, Fang Han, Xiao-Dong Sun

Abstract

Obesity is associated with adverse metabolic diseases including cardiovascular disease (CVD) and chronic kidney disease (CKD). These obesity-related diseases are highly associated with excess fat accumulation in adipose tissue. However, emerging evidence indicates that visceral adiposity associates more with metabolic and cardiovascular risk factors. Perirenal adipose tissue, surrounding the kidney, is originally thought to provides only mechanical support for kidney. However, more studies demonstrated perirenal adipose tissue have a closer association with renal disease than other visceral fat deposits in obesity. Additionally, perirenal adipose tissue is also an independent risk factor for CKD and even associated more with CVD. Thus, perirenal adipose tissue may be a connection of CVD with CKD. Here, we will provide an overview of the perirenal adipose tissue, a neglected visceral adipose tissue, and the roles of perirenal adipose tissue linking with CVD and CKD and highlight the perirenal adipose tissue as a potential strategy for future therapeutics against obesity-related disease.

Keywords: Abdominal fat; Adipose tissue; Cardiovascular diseases; Endothelium; Kidney diseases; Obesity.

Conflict of interest statement

Conflict-of-interest statement: Authors declare no conflict of interests for this article.

©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.

Figures

Figure 1
Figure 1
Potential mechanism for participation of perirenal adipose tissue in chronic kidney disease and cardiovascular disease. FFA: Free fatty acids; NO: Nitric oxide; RAAS: Renin-Angiotensin-Aldosterone System.

References

    1. Landrier JF, Derghal A, Mounien L. MicroRNAs in Obesity and Related Metabolic Disorders. Cells. 2019:8.
    1. Ghasemi A, Hashemy SI, Azimi-Nezhad M, Dehghani A, Saeidi J, Mohtashami M. The cross-talk between adipokines and miRNAs in health and obesity-mediated diseases. Clin Chim Acta. 2019;499:41–53.
    1. Heinonen S, Jokinen R, Rissanen A, Pietiläinen KH. White adipose tissue mitochondrial metabolism in health and in obesity. Obes Rev. 2020;21:e12958.
    1. Echouffo-Tcheugui JB, Short MI, Xanthakis V, Field P, Sponholtz TR, Larson MG, Vasan RS. Natural History of Obesity Subphenotypes: Dynamic Changes Over Two Decades and Prognosis in the Framingham Heart Study. J Clin Endocrinol Metab. 2019;104:738–752.
    1. Katsiki N, Anagnostis P, Kotsa K, Goulis DG, Mikhailidis DP. Obesity, Metabolic Syndrome and the Risk of Microvascular Complications in Patients with Diabetes mellitus. Curr Pharm Des. 2019;25:2051–2059.
    1. Lopes LL, Bressan J, Peluzio MDCG, Hermsdorff HHM. LINE-1 in Obesity and Cardiometabolic Diseases: A Systematic Review. J Am Coll Nutr. 2019;38:478–484.
    1. Martin-Calvo N, Moreno-Galarraga L, Martinez-Gonzalez MA. Association between Body Mass Index, Waist-to-Height Ratio and Adiposity in Children: A Systematic Review and Meta-Analysis. Nutrients. 2016:8.
    1. Deurenberg P, Yap M. The assessment of obesity: methods for measuring body fat and global prevalence of obesity. Baillieres Best Pract Res Clin Endocrinol Metab. 1999;13:1–11.
    1. Ferreira TDS, Barreto Silva MI, da Costa MS, Pontes KSDS, Castro FG, Antunes VP, Rosina KTC, Menna Barreto APM, Souza E, Klein MRST. High abdominal adiposity and low phase angle in overweight renal transplant recipients. Clin Transplant. 2019;33:e13654.
    1. Mulligan AA, Lentjes MAH, Luben RN, Wareham NJ, Khaw KT. Changes in waist circumference and risk of all-cause and CVD mortality: results from the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) cohort study. BMC Cardiovasc Disord. 2019;19:238.
    1. Bi X, Tey SL, Leong C, Quek R, Loo YT, Henry CJ. Correlation of adiposity indices with cardiovascular disease risk factors in healthy adults of Singapore: a cross-sectional study. BMC Obes. 2016;3:33.
    1. Scheja L, Heeren J. The endocrine function of adipose tissues in health and cardiometabolic disease. Nat Rev Endocrinol. 2019;15:507–524.
    1. Zhu Q, Scherer PE. Immunologic and endocrine functions of adipose tissue: implications for kidney disease. Nat Rev Nephrol. 2018;14:105–120.
    1. Shuster A, Patlas M, Pinthus JH, Mourtzakis M. The clinical importance of visceral adiposity: a critical review of methods for visceral adipose tissue analysis. Br J Radiol. 2012;85:1–10.
    1. Bays H. Central obesity as a clinical marker of adiposopathy; increased visceral adiposity as a surrogate marker for global fat dysfunction. Curr Opin Endocrinol Diabetes Obes. 2014;21:345–351.
    1. Mahabadi AA, Massaro JM, Rosito GA, Levy D, Murabito JM, Wolf PA, O'Donnell CJ, Fox CS, Hoffmann U. Association of pericardial fat, intrathoracic fat, and visceral abdominal fat with cardiovascular disease burden: the Framingham Heart Study. Eur Heart J. 2009;30:850–856.
    1. Sun X, Han F, Miao W, Hou N, Cao Z, Zhang G. Sonographic evaluation of para- and perirenal fat thickness is an independent predictor of early kidney damage in obese patients. Int Urol Nephrol. 2013;45:1589–1595.
    1. Karastergiou K, Fried SK. Multiple adipose depots increase cardiovascular risk via local and systemic effects. Curr Atheroscler Rep. 2013;15:361.
    1. D'Marco L, Salazar J, Cortez M, Salazar M, Wettel M, Lima-Martínez M, Rojas E, Roque W, Bermúdez V. Perirenal fat thickness is associated with metabolic risk factors in patients with chronic kidney disease. Kidney Res Clin Pract. 2019;38:365–372.
    1. Geraci G, Zammuto MM, Mattina A, Zanoli L, Geraci C, Granata A, Nardi E, Fatuzzo PM, Cottone S, Mulè G. Para-perirenal distribution of body fat is associated with reduced glomerular filtration rate regardless of other indices of adiposity in hypertensive patients. J Clin Hypertens (Greenwich) 2018;20:1438–1446.
    1. Lamacchia O, Nicastro V, Camarchio D, Valente U, Grisorio R, Gesualdo L, Cignarelli M. Para- and perirenal fat thickness is an independent predictor of chronic kidney disease, increased renal resistance index and hyperuricaemia in type-2 diabetic patients. Nephrol Dial Transplant. 2011;26:892–898.
    1. Liu BX, Sun W, Kong XQ. Perirenal Fat: A Unique Fat Pad and Potential Target for Cardiovascular Disease. Angiology. 2019;70:584–593.
    1. Marx WJ, Patel SK. Renal fascia: its radiographic importance. Urology. 1979;13:1–7.
    1. Shi Z, Chen WW, Xiong XQ, Han Y, Zhou YB, Zhang F, Gao XY, Zhu GQ. Sympathetic activation by chemical stimulation of white adipose tissues in rats. J Appl Physiol (1985) 2012;112:1008–1014.
    1. Tanuma Y, Ohata M, Ito T, Yokochi C. Possible function of human brown adipose tissue as suggested by observation on perirenal brown fats from necropsy cases of variable age groups. Arch Histol Jpn. 1976;39:117–145.
    1. Tanuma Y, Tamamoto M, Ito T, Yokochi C. The occurrence of brown adipose tissue in perirenal fat in Japanese. Arch Histol Jpn. 1975;38:43–70.
    1. Efremova A, Senzacqua M, Venema W, Isakov E, Di Vincenzo A, Zingaretti MC, Protasoni M, Thomski M, Giordano A, Cinti S. A large proportion of mediastinal and perirenal visceral fat of Siberian adult people is formed by UCP1 immunoreactive multilocular and paucilocular adipocytes. J Physiol Biochem. 2019
    1. Lau WB, Ohashi K, Wang Y, Ogawa H, Murohara T, Ma XL, Ouchi N. Role of Adipokines in Cardiovascular Disease. Circ J. 2017;81:920–928.
    1. Meyers MA, Friedenberg RM, King MC, Meng CH. The significance of the renal capsular arteries. Br J Radiol. 1967;40:949–956.
    1. Czaja K, Lakomy M, Kaleczyc J, Barb CR, Rampacek GB, Kraeling RR. Leptin receptors, NPY, and tyrosine hydroxylase in autonomic neurons supplying fat depots in a pig. Biochem Biophys Res Commun. 2002;293:1138–1144.
    1. Kim JH, Han EH, Jin ZW, Lee HK, Fujimiya M, Murakami G, Cho BH. Fetal topographical anatomy of the upper abdominal lymphatics: its specific features in comparison with other abdominopelvic regions. Anat Rec (Hoboken) 2012;295:91–104.
    1. Jones DW, Kim JS, Andrew ME, Kim SJ, Hong YP. Body mass index and blood pressure in Korean men and women: the Korean National Blood Pressure Survey. J Hypertens. 1994;12:1433–1437.
    1. Graffy PM, Pickhardt PJ. Quantification of hepatic and visceral fat by CT and MR imaging: relevance to the obesity epidemic, metabolic syndrome and NAFLD. Br J Radiol. 2016;89:20151024.
    1. Seabolt LA, Welch EB, Silver HJ. Imaging methods for analyzing body composition in human obesity and cardiometabolic disease. Ann N Y Acad Sci. 2015;1353:41–59.
    1. Favre G, Grangeon-Chapon C, Raffaelli C, François-Chalmin F, Iannelli A, Esnault V. Perirenal fat thickness measured with computed tomography is a reliable estimate of perirenal fat mass. PLoS One. 2017;12:e0175561.
    1. Tripathy P, Sahu A, Sahu M, Nagy A. Ultrasonographic evaluation of intra-abdominal fat distribution and study of its influence on subclinical atherosclerosis in women with polycystic ovarian syndrome. Eur J Obstet Gynecol Reprod Biol. 2017;217:18–22.
    1. Armellini F, Zamboni M, Rigo L, Todesco T, Bergamo-Andreis IA, Procacci C, Bosello O. The contribution of sonography to the measurement of intra-abdominal fat. J Clin Ultrasound. 1990;18:563–567.
    1. Kawasaki S, Aoki K, Hasegawa O, Numata K, Tanaka K, Shibata N, Shimada S, Okamura A, Terauchi Y. Sonographic evaluation of visceral fat by measuring para- and perirenal fat. J Clin Ultrasound. 2008;36:129–133.
    1. De Pergola G, Campobasso N, Nardecchia A, Triggiani V, Caccavo D, Gesualdo L, Silvestris F, Manno C. Para- and perirenal ultrasonographic fat thickness is associated with 24-hours mean diastolic blood pressure levels in overweight and obese subjects. BMC Cardiovasc Disord. 2015;15:108.
    1. Ricci MA, Scavizzi M, Ministrini S, De Vuono S, Pucci G, Lupattelli G. Morbid obesity and hypertension: The role of perirenal fat. J Clin Hypertens (Greenwich) 2018;20:1430–1437.
    1. Weisinger JR, Kempson RL, Eldridge FL, Swenson RS. The nephrotic syndrome: a complication of massive obesity. Ann Intern Med. 1974;81:440–447.
    1. Hsu CY, McCulloch CE, Iribarren C, Darbinian J, Go AS. Body mass index and risk for end-stage renal disease. Ann Intern Med. 2006;144:21–28.
    1. Othman M, Kawar B, El Nahas AM. Influence of obesity on progression of non-diabetic chronic kidney disease: a retrospective cohort study. Nephron Clin Pract. 2009;113:c16–c23.
    1. Klausen KP, Parving HH, Scharling H, Jensen JS. Microalbuminuria and obesity: impact on cardiovascular disease and mortality. Clin Endocrinol (Oxf) 2009;71:40–45.
    1. Ejerblad E, Fored CM, Lindblad P, Fryzek J, McLaughlin JK, Nyrén O. Obesity and risk for chronic renal failure. J Am Soc Nephrol. 2006;17:1695–1702.
    1. Bonnet F, Marre M, Halimi JM, Stengel B, Lange C, Laville M, Tichet J, Balkau B. Larger waist circumference is a predictive factor for the occurrence of microalbuminuria in a non-diabetic population. Arch Mal Coeur Vaiss. 2006;99:660–662.
    1. Pinto-Sietsma SJ, Navis G, Janssen WM, de Zeeuw D, Gans RO, de Jong PE PREVEND Study Group. A central body fat distribution is related to renal function impairment, even in lean subjects. Am J Kidney Dis. 2003;41:733–741.
    1. Foster MC, Hwang SJ, Porter SA, Massaro JM, Hoffmann U, Fox CS. Fatty kidney, hypertension, and chronic kidney disease: the Framingham Heart Study. Hypertension. 2011;58:784–790.
    1. Han F, Hou N, Miao W, Sun X. Correlation of ultrasonographic measurement of intrarenal arterial resistance index with microalbuminuria in nonhypertensive, nondiabetic obese patients. Int Urol Nephrol. 2013;45:1039–1045.
    1. Rea DJ, Heimbach JK, Grande JP, Textor SC, Taler SJ, Prieto M, Larson TS, Cosio FG, Stegall MD. Glomerular volume and renal histology in obese and non-obese living kidney donors. Kidney Int. 2006;70:1636–1641.
    1. Hall ME, do Carmo JM, da Silva AA, Juncos LA, Wang Z, Hall JE. Obesity, hypertension, and chronic kidney disease. Int J Nephrol Renovasc Dis. 2014;7:75–88.
    1. Hall JE, Crook ED, Jones DW, Wofford MR, Dubbert PM. Mechanisms of obesity-associated cardiovascular and renal disease. Am J Med Sci. 2002;324:127–137.
    1. Montani JP, Carroll JF, Dwyer TM, Antic V, Yang Z, Dulloo AG. Ectopic fat storage in heart, blood vessels and kidneys in the pathogenesis of cardiovascular diseases. Int J Obes Relat Metab Disord. 2004;28 Suppl 4:S58–S65.
    1. Hou N, Han F, Wang M, Huang N, Zhao J, Liu X, Sun X. Perirenal fat associated with microalbuminuria in obese rats. Int Urol Nephrol. 2014;46:839–845.
    1. Adeosun SO, Gordon DM, Weeks MF, Moore KH, Hall JE, Hinds TD, Jr, Stec DE. Loss of biliverdin reductase-A promotes lipid accumulation and lipotoxicity in mouse proximal tubule cells. Am J Physiol Renal Physiol. 2018;315:F323–F331.
    1. Sun X, Yu Y, Han L. High FFA levels related to microalbuminuria and uncoupling of VEGF-NO axis in obese rats. Int Urol Nephrol. 2013;45:1197–1207.
    1. Hou N, Huang N, Han F, Zhao J, Liu X, Sun X. Protective effects of adiponectin on uncoupling of glomerular VEGF-NO axis in early streptozotocin-induced type 2 diabetic rats. Int Urol Nephrol. 2014;46:2045–2051.
    1. Katsiki N, Athyros VG, Mikhailidis DP. Abnormal Peri-Organ or Intra-organ Fat (APIFat) Deposition: An Underestimated Predictor of Vascular Risk? Curr Vasc Pharmacol. 2016;14:432–441.
    1. Ma S, Zhu XY, Eirin A, Woollard JR, Jordan KL, Tang H, Lerman A, Lerman LO. Perirenal Fat Promotes Renal Arterial Endothelial Dysfunction in Obese Swine through Tumor Necrosis Factor-α. J Urol. 2016;195:1152–1159.
    1. Liu Y, Wang L, Luo M, Chen N, Deng X, He J, Zhang L, Luo P, Wu J. Inhibition of PAI-1 attenuates perirenal fat inflammation and the associated nephropathy in high-fat diet-induced obese mice. Am J Physiol Endocrinol Metab. 2019;316:E260–E267.
    1. Li H, Li M, Liu P, Wang Y, Zhang H, Li H, Yang S, Song Y, Yin Y, Gao L, Cheng S, Cai J, Tian G. Telmisartan Ameliorates Nephropathy in Metabolic Syndrome by Reducing Leptin Release From Perirenal Adipose Tissue. Hypertension. 2016;68:478–490.
    1. Michaud A, Drolet R, Noël S, Paris G, Tchernof A. Visceral fat accumulation is an indicator of adipose tissue macrophage infiltration in women. Metabolism. 2012;61:689–698.
    1. Ndisang JF, Jadhav A, Mishra M. The heme oxygenase system suppresses perirenal visceral adiposity, abates renal inflammation and ameliorates diabetic nephropathy in Zucker diabetic fatty rats. PLoS One. 2014;9:e87936.
    1. Li Z, Woollard JR, Wang S, Korsmo MJ, Ebrahimi B, Grande JP, Textor SC, Lerman A, Lerman LO. Increased glomerular filtration rate in early metabolic syndrome is associated with renal adiposity and microvascular proliferation. Am J Physiol Renal Physiol. 2011;301:F1078–F1087.
    1. Manno C, Campobasso N, Nardecchia A, Triggiani V, Zupo R, Gesualdo L, Silvestris F, De Pergola G. Relationship of para- and perirenal fat and epicardial fat with metabolic parameters in overweight and obese subjects. Eat Weight Disord. 2019;24:67–72.
    1. Rao A, Pandya V, Whaley-Connell A. Obesity and insulin resistance in resistant hypertension: implications for the kidney. Adv Chronic Kidney Dis. 2015;22:211–217.
    1. Yudkin JS, Forrest RD, Jackson CA. Microalbuminuria as predictor of vascular disease in non-diabetic subjects. Islington Diabetes Survey. Lancet. 1988;2:530–533.
    1. Wachtell K, Olsen MH, Dahlöf B, Devereux RB, Kjeldsen SE, Nieminen MS, Okin PM, Papademetriou V, Mogensen CE, Borch-Johnsen K, Ibsen H. Microalbuminuria in hypertensive patients with electrocardiographic left ventricular hypertrophy: the LIFE study. J Hypertens. 2002;20:405–412.
    1. Hillege HL, Fidler V, Diercks GF, van Gilst WH, de Zeeuw D, van Veldhuisen DJ, Gans RO, Janssen WM, Grobbee DE, de Jong PE Prevention of Renal and Vascular End Stage Disease (PREVEND) Study Group. Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation. 2002;106:1777–1782.
    1. Tebbe U, Bramlage P, Thoenes M, Paar WD, Danchin N, Volpe M, Schrader J, Noll G, Burnier M, Böhm M. Prevalence of microalbuminuria and its associated cardiovascular risk: German and Swiss results of the recent global i-SEARCH survey. Swiss Med Wkly. 2009;139:473–480.
    1. Gerstein HC, Mann JF, Yi Q, Zinman B, Dinneen SF, Hoogwerf B, Hallé JP, Young J, Rashkow A, Joyce C, Nawaz S, Yusuf S HOPE Study Investigators. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA. 2001;286:421–426.
    1. Kumar Jha P, Ete T, Malviya A, Kumar Das C, Saha SK, Nath D, Kapoor M, Mishra A. Microalbuminuria: Correlation With Prevalence and Severity of Coronary Artery Disease in Non-Diabetics. J Clin Med Res. 2017;9:838–843.
    1. Yuyun MF, Khaw KT, Luben R, Welch A, Bingham S, Day NE, Wareham NJ European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) population study. Microalbuminuria independently predicts all-cause and cardiovascular mortality in a British population: The European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) population study. Int J Epidemiol. 2004;33:189–198.
    1. Bajaj NS, Singh A, Zhou W, Gupta A, Fujikura K, Byrne C, Harms HJ, Osborne MT, Bravo P, Andrikopolou E, Divakaran S, Bibbo CF, Hainer J, Skali H, Taqueti V, Steigner M, Dorbala S, Charytan DM, Prabhu SD, Blankstein R, Deo RC, Solomon SD, Di Carli MF. Coronary Microvascular Dysfunction, Left Ventricular Remodeling, and Clinical Outcomes in Patients With Chronic Kidney Impairment. Circulation. 2020;141:21–33.
    1. Grima P, Guido M, Zizza A, Chiavaroli R. Sonographically measured perirenal fat thickness: an early predictor of atherosclerosis in HIV-1-infected patients receiving highly active antiretroviral therapy? J Clin Ultrasound. 2010;38:190–195.
    1. Bassols J, Martínez-Calcerrada JM, Prats-Puig A, Carreras-Badosa G, Xargay-Torrent S, Lizarraga-Mollinedo E, Feliu-Alsina M, Riera-Pérez E, Osiniri I, de Zegher F, Ibáñez L, López-Bermejo A. Perirenal fat is related to carotid intima-media thickness in children. Int J Obes (Lond) 2018;42:641–647.
    1. Kotsis V, Stabouli S, Papakatsika S, Rizos Z, Parati G. Mechanisms of obesity-induced hypertension. Hypertens Res. 2010;33:386–393.
    1. Roever L, Resende ES, Veloso FC, Diniz AL, Penha-Silva N, Casella-Filho A, Dourado PM, Chagas AC. Perirenal Fat and Association With Metabolic Risk Factors: The Uberlândia Heart Study. Medicine (Baltimore) 2015;94:e1105.
    1. Tanida M, Iwashita S, Ootsuka Y, Terui N, Suzuki M. Leptin injection into white adipose tissue elevates renal sympathetic nerve activity dose-dependently through the afferent nerves pathway in rats. Neurosci Lett. 2000;293:107–110.
    1. Grima P, Guido M, Chiavaroli R, Zizza A. Ultrasound-assessed perirenal fat is related to increased ophthalmic artery resistance index in HIV-1 patients. Cardiovasc Ultrasound. 2010;8:24.
    1. Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed-Enevoldsen A. Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia. 1989;32:219–226.
    1. Mateo-Gallego R, Marco-Benedí V, Perez-Calahorra S, Bea AM, Baila-Rueda L, Lamiquiz-Moneo I, de Castro-Orós I, Cenarro A, Civeira F. Energy-restricted, high-protein diets more effectively impact cardiometabolic profile in overweight and obese women than lower-protein diets. Clin Nutr. 2017;36:371–379.
    1. Parrish CC, Pathy DA, Angel A. Dietary fish oils limit adipose tissue hypertrophy in rats. Metabolism. 1990;39:217–219.
    1. Yan H, Cao S, Li Y, Zhang H, Liu J. Reduced meal frequency alleviates high-fat diet-induced lipid accumulation and inflammation in adipose tissue of pigs under the circumstance of fixed feed allowance. Eur J Nutr. 2020;59:595–608.
    1. Zhao SQ, Shi HJ, Zheng NN. [Effects of different intensity interval exercise of 6 weeks on body composition of obese rats] Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2019;35:326–330.
    1. Jespersen NZ, Feizi A, Andersen ES, Heywood S, Hattel HB, Daugaard S, Peijs L, Bagi P, Feldt-Rasmussen B, Schultz HS, Hansen NS, Krogh-Madsen R, Pedersen BK, Petrovic N, Nielsen S, Scheele C. Heterogeneity in the perirenal region of humans suggests presence of dormant brown adipose tissue that contains brown fat precursor cells. Mol Metab. 2019;24:30–43.
    1. Warner A, Kjellstedt A, Carreras A, Böttcher G, Peng XR, Seale P, Oakes N, Lindén D. Activation of β3-adrenoceptors increases in vivo free fatty acid uptake and utilization in brown but not white fat depots in high-fat-fed rats. Am J Physiol Endocrinol Metab. 2016;311:E901–E910.

Source: PubMed

3
Subscribe