Abstract
Glucolipid metabolic disease (GLMD), a complex of interrelated disorders in glucose and lipid metabolism, has become one of the leading chronic diseases causing public and clinical problem worldwide. As the metabolism of lipid and glucose is a highly coordinated process under both physiological and diseased conditions, the impairment in the signals corresponding to the metabolism of either lipid or glucose represents the common mechanism underlying the pathogenesis of GLMD. The liver and adipose tissue are the major metabolic organs responsible for energy utilization and storage, respectively. This review article aims to summarize the current advances in the investigation of the functional roles and the underling mechanisms of the interplay between the liver and adipose tissue in the modulation of GLMD development. Fibroblast growth factor 21 (FGF21) and adiponectin represent the two major hormones secreted from the liver and adipose tissues, respectively. FGF21 exerts pleiotropic effects on regulating glucose and lipid homeostasis majorly through inducing the expression and secretion of adiponectin. Therefore, FGF21-adiponectin axis functions as the key mediator for the crosstalk between the liver and adipose tissue to exert the beneficial effects on the maintenance of the homeostasis of energy consumption. The liver- and adipose tissue-derived factors with pleiotropic effects on regulating of lipid and glucose metabolism function as the key mediator for the crosstalk between these two highly active metabolic organs, thereby coordinating the initiation and development of GLMD.
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Sul HS, Latasa MJ, Moon Y, Kim KH. Regulation of the fatty acid synthase promoter by insulin. J Nutr 2000;130:315S–320S.
Dentin R, Girard J, Postic C. Carbohydrate responsive element binding protein (ChREBP) and sterol regulatory element binding protein-1c (SREBP-1c): two key regulators of glucose metabolism and lipid synthesis in liver. Biochimie 2005;87:81–86.
Bechmann LP, Hannivoort RA, Gerken G, Hotamisligil GS, Trauner M, Canbay A. The interaction of hepatic lipid and glucose metabolism in liver diseases. J Hepatol 2012;56:952–964.
Aguilar M, Bhuket T, Torres S, Liu B, Wong RJ. Prevalence of the metabolic syndrome in the United States, 2003–2012. JAMA 2015;313:1973–1974.
Parhofer KG. Interaction between glucose and lipid metabolism: more than diabetic dyslipidemia. Diabetes Metab J 2015;39:353–362.
Rachek LI. Free fatty acids and skeletal muscle insulin resistance. Prog Mol Biol Transl Sci 2014;121:267–292.
Tenenbaum A, Motro M, Fisman EZ, Schwammenthal E, Adler Y, Goldenberg I, et al. Peroxisome proliferatoractivated receptor ligand bezafibrate for prevention of type 2 diabetes mellitus in patients with coronary artery disease. Circulation 2004;109:2197–2202.
Tenenbaum H, Behar S, Boyko V, Adler Y, Fisman EZ, Tanne D, et al. Long-term effect of bezafibrate on pancreatic beta-cell function and insulin resistance in patients with diabetes. Atherosclerosis 2007;194:265–271.
Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 2010;375:735–742.
Hu X, Wang M, Bei W, Han Z, Guo J. The Chinese herbal medicine FTZ attenuates insulin resistance via IRS1 and PI3K in vitro and in rats with metabolic syndrome. J Transl Med 2014;12:47.
Indrakusuma I, Sell H, Eckel J. Novel mediators of adipose tissue and muscle crosstalk. Curr Obes Rep 2015;4:411–417.
Scherer PE. Adipose tissue: from lipid storage compartment to endocrine organ. Diabetes 2006;55:1537–1545.
Hui X, Feng T, Liu Q, Gao Y, Xu A. The FGF21-adiponectin axis in controlling energy and vascular homeostasis. J Molecul Cell Biol 2016;8:110–119.
Potthoff MJ, Kliewer SA, Mangelsdorf DJ. Endocrine fibroblast growth factors 15/19 and 21: from feast to famine. Genes Development 2012;26:312–324.
Badman MK, Pissios P, Kennedy AR, Koukos G, Flier JS, Maratos-Flier E. Hepatic fibroblast growth factor 21 is regulated by PPAR alpha and is a key mediator of hepatic lipid metabolism in ketotic states. Cell Metab 2007;5:426–437.
Dutchak PA, Katafuchi T, Bookout AL, Choi JH, Yu RT, Mangelsdorf DJ, et al. Fibroblast growth factor-21 regulates PPAR gamma activity and the antidiabetic actions of thiazolidinediones. Cell 2012;148:556–567.
Kharitonenkov A, Dunbar JD, Bina HA, Bright S, Moyers JS, Zhang C, et al. FGF-21/FGF-21 receptor interaction and activation is determined by beta Klotho. J Cellular Physiol 2008;215:1–7.
Véniant MM, Hale C, Helmering J, Chen MM, Stanislaus S, Busby J, et al. FGF21 promotes metabolic homeostasis via white adipose and leptin in mice. PLoS One 2012;7:e40164.
Hui X, Lam KS, Vanhoutte PM, Xu A. Adiponectin and cardiovascular health: an update. British J Pharmacol 2012;165:574–590.
Xu A, Vanhoutte PM. Adiponectin and adipocyte fatty acid binding protein in the pathogenesis of cardiovascular disease. Am J Physiol Heart Circ Physiol 2012;302:H1231–H1240.
Ding X, Boney-Montoya J, Owen BM, Bookout AL, Coate KC, Mangelsdorf DJ, et al. Beta Klotho is required for fibroblast growth factor 21 effects on growth and metabolism. Cell Metab 2012;16:387–393.
Lin Z, Tian H, Lam KS, Lin S, Hoo RC, Konishi M, et al. Adiponectin mediates the metabolic effects of FGF21 on glucose homeostasis and insulin sensitivity in mice. Cell Metab 2013;17:779–789.
Holland WL, Adams AC, Brozinick JT, Bui HH, Miyauchi Y, Kusminski CM, et al. An FGF21-adiponectin-ceramide axis controls energy expenditure and insulin action in mice. Cell Metab 2013:17:790-797.
Berg AH, Combs TP, Du X, Brownlee M, Scherer PE. The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 2001;7:947–953.
Ye D, Wang Y, Li H, Jia W, Man K, Lo CM, et al. Fibroblast growth factor 21 protects against acetaminophen-induced hepatotoxicity by potentiating peroxisome proliferatoractivated receptor coactivator protein-1alpha-mediated antioxidant capacity in mice. Hepatology 2014;60:977–989.
Arner P, Pettersson A, Mitchell PJ, Dunbar JD, Kharitonenkov A, Rydén M. FGF21 attenuates lipolysis in human adipocytes—a possible link to improved insulin sensitivity. FEBS Lett 2008;582:1725–1730.
Qiao L, Kinney B, Schaack J, Shao J. Adiponectin inhibits lipolysis in mouse adipocytes. Diabetes 2011;60:1519–1527.
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Ye, Dw., Rong, Xl., Xu, Am. et al. Liver-adipose tissue crosstalk: A key player in the pathogenesis of glucolipid metabolic disease. Chin. J. Integr. Med. 23, 410–414 (2017). https://doi.org/10.1007/s11655-017-2810-4
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DOI: https://doi.org/10.1007/s11655-017-2810-4