Irisin Inhibits Hepatic Cholesterol Synthesis via AMPK-SREBP2 Signaling

EBioMedicine

Volumn 6, Issue , 2016, Pages 139-148

  Tang, Hong ^a   Yu, Ruili ^a   Liu, Shiying ^a   Huwatibieke, Bahetiyaer ^a   Li, Ziru ^b   Zhang, Weizhen ^a,b  

^a PEKING UNIVERSITY HEALTH SCIENCE CENTER   (China)

^b UNIVERSITY OF MICHIGAN HEALTH SYSTEM   (United States)

Author keywords

AMPK; Cholesterol; Irisin; Liver; SREBP2

Indexed keywords

HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; IRISIN; STEROL REGULATORY ELEMENT BINDING PROTEIN 2; CHOLESTEROL; FIBRONECTIN; FNDC5 PROTEIN, MOUSE; SREBF2 PROTEIN, MOUSE;

ANIMAL CELL; ARTICLE; CHOLESTEROL SYNTHESIS; FAST PROTEIN LIQUID CHROMATOGRAPHY; GENE EXPRESSION; GLUCOSE TOLERANCE TEST; HUMAN; HUMAN CELL; HYPERCHOLESTEROLEMIA; IMMUNOFLUORESCENCE TEST; INSULIN TOLERANCE TEST; MALE; MOUSE; NONHUMAN; OBESITY; PRIORITY JOURNAL; WESTERN BLOTTING; ADVERSE EFFECTS; ANIMAL; BIOSYNTHESIS; BLOOD; CHEMICALLY INDUCED; CHEMISTRY; GENE EXPRESSION REGULATION; GENETICS; HEP-G2 CELL LINE; LIPID DIET; LIVER; METABOLISM; SIGNAL TRANSDUCTION;

AMP-ACTIVATED PROTEIN KINASES; ANIMALS; CHOLESTEROL; DIET, HIGH-FAT; FIBRONECTINS; GENE EXPRESSION REGULATION; HEP G2 CELLS; HUMANS; LIVER; MICE; OBESITY; SIGNAL TRANSDUCTION; STEROL REGULATORY ELEMENT BINDING PROTEIN 2;

EID: 84959377737     PISSN: None     EISSN: 23523964     Source Type: Journal    
DOI: 10.1016/j.ebiom.2016.02.041     Document Type: Article

References (56)

1. Aronis K.N., Moreno M., Polyzos S.A., Moreno-Navarrete J.M., Ricart W., Delgado E., De La Hera J., Sahin-Efe A., Chamberland J.P., Berman R., Spiro A., Vokonas P., Fernandez-Real J.M., Mantzoros C.S. Circulating irisin levels and coronary heart disease: association with future acute coronary syndrome and major adverse cardiovascular events. Int. J. Obes. 2015, 39:156-161.
2. Bilski J., Mazur-Bialy A.I., Brzozowski B., Magierowski M., Jasnos K., Krzysiek-Maczka G., Urbanczyk K., Ptak-Belowska A., Zwolinska-Wcislo M., Mach T., Brzozowski T. Moderate exercise training attenuates the severity of experimental rodent colitis: the importance of crosstalk between adipose tissue and skeletal muscles. Mediat. Inflamm. 2015, 2015:605071.
3. Bostrom P., Wu J., Jedrychowski M.P., Korde A., Ye L., Lo J.C., Rasbach K.A., Bostrom E.A., Choi J.H., Long J.Z., Kajimura S., Zingaretti M.C., Vind B.F., Tu H., Cinti S., Hojlund K., Gygi S.P., Spiegelman B.M. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012, 481:463-468.
4. Chen L., Shu Y., Liang X., Chen E.C., Yee S.W., Zur A.A., Li S., Xu L., Keshari K.R., Lin M.J., Chien H.C., Zhang Y., Morrissey K.M., Liu J., Ostrem J., Younger N.S., Kurhanewicz J., Shokat K.M., Ashrafi K., Giacomini K.M. OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. Proc. Natl. Acad. Sci. U. S. A. 2014, 111:9983-9988.
5. Choi E.S., Kim M.K., Song M.K., Kim J.M., Kim E.S., Chung W.J., Park K.S., Cho K.B., Hwang J.S., Jang B.K. Association between serum irisin levels and non-alcoholic fatty liver disease in health screen examinees. PLoS One 2014, 9.
6. Choi Y.K., Kim M.K., Bae K.H., Seo H.A., Jeong J.Y., Lee W.K., Kim J.G., Lee I.K., Park K.G. Serum irisin levels in new-onset type 2 diabetes. Diabetes Res. Clin. Pract. 2013, 100:96-101.
7. De La Iglesia R., Lopez-Legarrea P., Crujeiras A.B., Pardo M., Casanueva F.F., Zulet M.A., Martinez J.A. Plasma irisin depletion under energy restriction is associated with improvements in lipid profile in metabolic syndrome patients. Clin. Endocrinol. 2014, 81:306-311.
8. Duran I.D., Gulcelik N.E., Unal M., Topcuoglu C., Sezer S., Tuna M.M., Berker D., Guler S. Irisin levels in the progression of diabetes in sedentary women. Clin. Biochem 2015.
9. Ebert T., Focke D., Petroff D., Wurst U., Richter J., Bachmann A., Lossner U., Kralisch S., Kratzsch J., Beige J., Bast I., Anders M., Bluher M., Stumvoll M., Fasshauer M. Serum levels of the myokine irisin in relation to metabolic and renal function. Eur. J. Endocrinol. 2014, 170:501-506.
10. Ebert T., Kralisch S., Wurst U., Scholz M., Stumvoll M., Kovacs P., Fasshauer M., Tonjes A. Association of metabolic parameters and rs726344 in FNDC5 with serum irisin concentrations. Int. J. Obes. 2015.
11. Elhanati S., Kanfi Y., Varvak A., Roichman A., Carmel-Gross I., Barth S., Gibor G., Cohen H.Y. Multiple regulatory layers of SREBP1/2 by SIRT6. Cell Rep. 2013, 4:905-912.
12. Espes D., Lau J., Carlsson P.O. Increased levels of irisin in people with long-standing type 1 diabetes. Diabet. Med. 2015, 32:1172-1176.
13. Gibbons G.F., Attwell Thomas C.P., Pullinger C.R. The metabolic route by which oleate is converted into cholesterol in rat hepatocytes. Biochem. J. 1986, 235:19-24.
14. Goh E.H., Heimberg M. Effect of oleic acid and cholesterol on the activity of hepatic hydroxymethylglutaryl coenzyme A reductase. FEBS Lett. 1976, 63:209-210.
15. Hirsch H.J., Gross I., Pollak Y., Eldar-Geva T., Gross-Tsur V. Irisin and the metabolic phenotype of adults with Prader-Willi Syndrome. PLoS One 2015, 10.
16. Hou N., Han F., Sun X. The relationship between circulating irisin levels and endothelial function in lean and obese subjects. Clin. Endocrinol. 2015, 83:339-343.
17. Huh J.Y., Dincer F., Mesfum E., Mantzoros C.S. Irisin stimulates muscle growth-related genes and regulates adipocyte differentiation and metabolism in humans. Int. J. Obes. 2014, 38:1538-1544.
18. Huh J.Y., Panagiotou G., Mougios V., Brinkoetter M., Vamvini M.T., Schneider B.E., Mantzoros C.S. FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise. Metab. Clin. Exp. 2012, 61:1725-1738.
19. Kurdiova T., Balaz M., Vician M., Maderova D., Vlcek M., Valkovic L., Srbecky M., Imrich R., Kyselovicova O., Belan V., Jelok I., Wolfrum C., Klimes I., Krssak M., Zemkova E., Gasperikova D., Ukropec J., Ukropcova B. Effects of obesity, diabetes and exercise on Fndc5 gene expression and irisin release in human skeletal muscle and adipose tissue: in vivo and in vitro studies. J. Physiol. 2014, 592:1091-1107.
20. Lee H.J., Lee J.O., Kim N., Kim J.K., Kim H.I., Lee Y.W., Kim S.J., Choi J.I., Oh Y., Kim J.H., Suyeon H., Park S.H., Kim H.S. Irisin, a novel myokine, regulates glucose uptake in skeletal muscle cells via AMPK. Mol. Endocrinol. 2015, 29:873-881.
21. Lee J.W., Choe S.S., Jang H., Kim J., Jeong H.W., Jo H., Jeong K.H., Tadi S., Park M.G., Kwak T.H., Man Kim J., Hyun D.H., Kim J.B. AMPK activation with glabridin ameliorates adiposity and lipid dysregulation in obesity. J. Lipid Res. 2012, 53:1277-1286.
22. Lee P., Linderman J.D., Smith S., Brychta R.J., Wang J., Idelson C., Perron R.M., Werner C.D., Phan G.Q., Kammula U.S., Kebebew E., Pacak K., Chen K.Y., Celi F.S. Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab. 2014, 19:302-309.
23. Li D.J., Huang F., Lu W.J., Jiang G.J., Deng Y.P., Shen F.M. Metformin promotes irisin release from murine skeletal muscle independently of AMP-activated protein kinase activation. Acta Physiol (Oxf.) 2015, 213:711-721.
24. Li M., Yang M., Zhou X., Fang X., Hu W., Zhu W., Wang C., Liu D., Li S., Liu H., Yang G., Li L. Elevated circulating levels of irisin and the effect of metformin treatment in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 2015, 100:1485-1493.
25. Liu J.J., Wong M.D., Toy W.C., Tan C.S., Liu S., Ng X.W., Tavintharan S., Sum C.F., Lim S.C. Lower circulating irisin is associated with type 2 diabetes mellitus. J. Diabetes Complicat. 2013, 27:365-369.
26. Liu S., Jing F., Yu C., Gao L., Qin Y., Zhao J. AICAR-induced activation of AMPK inhibits TSH/SREBP-2/HMGCR pathway in liver. PLoS One 2015, 10.
27. Liu T.Y., Shi C.X., Gao R., Sun H.J., Xiong X.Q., Ding L., Chen Q., Li Y.H., Wang J.J., Kang Y.M., Zhu G.Q. Irisin inhibits hepatic gluconeogenesis and increases glycogen synthesis via the PI3K/Akt pathway in type 2 diabetic mice and hepatocytes. Clin. Sci. (Lond.) 2015, 129:839-850.
28. Lopez-Legarrea P., De La Iglesia R., Crujeiras A.B., Pardo M., Casanueva F.F., Zulet M.A., Martinez J.A. Higher baseline irisin concentrations are associated with greater reductions in glycemia and insulinemia after weight loss in obese subjects. Nutr. Diabetes 2014, 4.
29. Ma W., Ding H., Gong X., Liu Z., Lin Y., Zhang Z., Lin G. Methyl protodioscin increases ABCA1 expression and cholesterol efflux while inhibiting gene expressions for synthesis of cholesterol and triglycerides by suppressing SREBP transcription and microRNA 33a/b levels. Atherosclerosis 2015, 239:566-570.
30. Miyamoto-Mikami E., Sato K., Kurihara T., Hasegawa N., Fujie S., Fujita S., Sanada K., Hamaoka T., Tabata I., Iemitsu M. Endurance training-induced increase in circulating irisin levels is associated with reduction of abdominal visceral fat in middle-aged and older adults. PLoS One 2015, 10.
31. Moreno-Navarrete J.M., Ortega F., Serrano M., Guerra E., Pardo G., Tinahones F., Ricart W., Fernandez-Real J.M. Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance. J. Clin. Endocrinol. Metab. 2013, 98:E769-E778.
32. Panagiotou G., Mu L., Na B., Mukamal K.J., Mantzoros C.S. Circulating irisin, omentin-1, and lipoprotein subparticles in adults at higher cardiovascular risk. Metab. Clin. Exp. 2014, 63:1265-1271.
33. Park M.J., Kim D.I., Choi J.H., Heo Y.R., Park S.H. New role of irisin in hepatocytes: the protective effect of hepatic steatosis in vitro. Cell. Signal. 2015, 27:1831-1839.
34. Polyzos S.A., Kountouras J., Anastasilakis A.D., Geladari E.V., Mantzoros C.S. Irisin in patients with nonalcoholic fatty liver disease. Metab. Clin. Exp. 2014, 63:207-217.
35. Polyzos S.A., Kountouras J., Anastasilakis A.D., Margouta A., Mantzoros C.S. Association between circulating irisin and homocysteine in patients with nonalcoholic fatty liver disease. Endocrine 2015, 49:560-562.
36. Quan H.Y., Kim Do Y., Chung S.H. Caffeine attenuates lipid accumulation via activation of AMP-activated protein kinase signaling pathway in HepG2 cells. BMB Rep. 2013, 46:207-212.
37. Rodriguez A., Becerril S., Mendez-Gimenez L., Ramirez B., Sainz N., Catalan V., Gomez-Ambrosi J., Fruhbeck G. Leptin administration activates irisin-induced myogenesis via nitric oxide-dependent mechanisms, but reduces its effect on subcutaneous fat browning in mice. Int. J. Obes. 2015, 39:397-407.
38. Samovski D., Sun J., Pietka T., Gross R.W., Eckel R.H., Su X., Stahl P.D., Abumrad N.A. Regulation of AMPK activation by CD36 links fatty acid uptake to beta-oxidation. Diabetes 2015, 64:353-359.
39. Shan T., Liang X., Bi P., Kuang S. Myostatin knockout drives browning of white adipose tissue through activating the AMPK-PGC1alpha-Fndc5 pathway in muscle. FASEB J. 2013, 27:1981-1989.
40. Song H., Wu F., Zhang Y., Wang F., Jiang M., Wang Z., Zhang M., Li S., Yang L., Wang X.L., Cui T., Tang D. Irisin promotes human umbilical vein endothelial cell proliferation through the ERK signaling pathway and partly suppresses high glucose-induced apoptosis. PLoS One 2014, 9.
41. Tang S., Zhang R., Jiang F., Wang J., Chen M., Peng D., Yan J., Wang S., Bao Y., Hu C., Jia W. Circulating irisin levels are associated with lipid and uric acid metabolism in a Chinese population. Clin. Exp. Pharmacol. Physiol. 2015.
42. Vaughan R.A., Gannon N.P., Barberena M.A., Garcia-Smith R., Bisoffi M., Mermier C.M., Conn C.A., Trujillo K.A. Characterization of the metabolic effects of irisin on skeletal muscle in vitro. Diabetes Obes. Metab. 2014, 16:711-718.
43. Wang C., Wang L., Li W., Yan F., Tian M., Wu C., Qi L., Wang X., Song J., Hou X., Chen L. Irisin has no effect on lipolysis in 3T3-L1 adipocytes or fatty acid metabolism in HepG2 hepatocytes. Endocrine 2015, 49:90-96.
44. Wen M.S., Wang C.Y., Lin S.L., Hung K.C. Decrease in irisin in patients with chronic kidney disease. PLoS One 2013, 8.
45. Wrann C.D., White J.P., Salogiannnis J., Laznik-Bogoslavski D., Wu J., Ma D., Lin J.D., Greenberg M.E., Spiegelman B.M. Exercise induces hippocampal BDNF through a PGC-1alpha/FNDC5 pathway. Cell Metab. 2013, 18:649-659.
46. Wu F., Song H., Zhang Y., Mu Q., Jiang M., Wang F., Zhang W., Li L., Li H., Wang Y., Zhang M., Li S., Yang L., Meng Y., Tang D. Irisin induces angiogenesis in human umbilical vein endothelial cells in vitro and in zebrafish embryos in vivo via activation of the ERK signaling pathway. PLoS One 2015, 10.
47. Wu J., Bostrom P., Sparks L.M., Ye L., Choi J.H., Giang A.H., Khandekar M., Virtanen K.A., Nuutila P., Schaart G., Huang K., Tu H., Van Marken Lichtenbelt W.D., Hoeks J., Enerback S., Schrauwen P., Spiegelman B.M. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 2012, 150:366-376.
48. Wu M.V., Bikopoulos G., Hung S., Ceddia R.B. Thermogenic capacity is antagonistically regulated in classical brown and white subcutaneous fat depots by high fat diet and endurance training in rats: impact on whole-body energy expenditure. J. Biol. Chem. 2014, 289:34129-34140.
49. Xiang L., Xiang G., Yue L., Zhang J., Zhao L. Circulating irisin levels are positively associated with endothelium-dependent vasodilation in newly diagnosed type 2 diabetic patients without clinical angiopathy. Atherosclerosis 2014, 235:328-333.
50. Xiong X.Q., Chen D., Sun H.J., Ding L., Wang J.J., Chen Q., Li Y.H., Zhou Y.B., Han Y., Zhang F., Gao X.Y., Kang Y.M., Zhu G.Q. FNDC5 overexpression and irisin ameliorate glucose/lipid metabolic derangements and enhance lipolysis in obesity. Biochim. Biophys. Acta 2015, 1852:1867-1875.
51. Yan B., Shi X., Zhang H., Pan L., Ma Z., Liu S., Liu Y., Li X., Yang S., Li Z. Association of serum irisin with metabolic syndrome in obese Chinese adults. PLoS One 2014, 9.
52. Yang Z., Chen X., Chen Y., Zhao Q. Decreased irisin secretion contributes to muscle insulin resistance in high-fat diet mice. Int. J. Clin. Exp. Pathol. 2015, 8:6490-6497.
53. Zhang H.J., Zhang X.F., Ma Z.M., Pan L.L., Chen Z., Han H.W., Han C.K., Zhuang X.J., Lu Y., Li X.J., Yang S.Y., Li X.Y. Irisin is inversely associated with intrahepatic triglyceride contents in obese adults. J. Hepatol. 2013, 59:557-562.
54. Zhang W., Chang L., Zhang C., Zhang R., Li Z., Chai B., Li J., Chen E., Mulholland M. Central and peripheral irisin differentially regulate blood pressure. Cardiovasc. Drugs Ther. 2015, 29:121-127.
55. Zhang Y., Li R., Meng Y., Li S., Donelan W., Zhao Y., Qi L., Zhang M., Wang X., Cui T., Yang L.J., Tang D. Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling. Diabetes 2014, 63:514-525.
56. Zhu D., Wang H., Zhang J., Zhang X., Xin C., Zhang F., Lee Y., Zhang L., Lian K., Yan W., Ma X., Liu Y., Tao L. Irisin improves endothelial function in type 2 diabetes through reducing oxidative/nitrative stresses. J. Mol. Cell. Cardiol. 2015, 87:138-147.