收稿日期: 2016-01-18
修回日期: 2016-03-08
网络出版日期: 2016-07-15
基金资助
国家自然科学基金(11075207,20871120)、中国科学院科教融合项目(KJRH2015-003)和中国科学院知识创新工程重大项目(KSCX2-EW-J-29)资助
Effect of autophagy on hepatic lipid metabolism in liver
Received date: 2016-01-18
Revised date: 2016-03-08
Online published: 2016-07-15
黄莹 , 张芳 , 丁文军 . 肝脏脂质代谢与自噬[J]. 中国科学院大学学报, 2016 , 33(4) : 570 -575 . DOI: 10.7523/j.issn.2095-6134.2016.04.020
It has been well demonstrated that lipid accumulation in liver of the obesity is involved in endoplasmic reticulum stress, mitochondria dysfunction, and lipotoxicity, which is associated with insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD).Autophagy has been considered to be an adaptive response to stress, contributing to cellular homeostasis.It has been found that autophagy is activated during hepatic lipid accumulation.Autophagy plays an essential role in maintaining hepatic lipid metabolism.This review summarizes recent studies to identify the molecular mechanism of autophagy maintaining hepatic lipid metabolism in the obesity.
Key words: obesity; liver; autophagy; lipid metabolism
[1] Musso G, Gambino R, Cassader M.Recent insights into hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD)[J].Progress in Lipid Research, 2009,48(1): 1-26.
[2] Marchesini G, Bugianesi E, Forlani G, et al.Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome[J].Hepatology, 2003,37(4): 917-923.
[3] Sanyal A J, Campbell-Sargent C, Mirshahi F, et al.Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities[J].Gastroenterology, 2001,120(5): 1 183-1 192.
[4] Neuschwander-Tetri B A.Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: the central role of nontriglyceride fatty acid metabolites[J].Hepatology, 2010,52(2): 774-788.
[5] Fu S, Yang L, Li P, et al.Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity[J].Nature, 2011,473(7 348): 528-531.
[6] Yin X M, Ding W X, Gao W T.Autophagy in the liver[J].Hepatology, 2008,47(5): 1 773-1 785.
[7] Sweeting H N.Measurement and definitions of obesity in childhood and adolescence: a field guide for the uninitiated[J].Nutrition Journal, 2007,6(1): 125-135.
[8] Zierath J R, Livingston J N, Thorne A, et al.Regional difference in insulin inhibition of non-esterified fatty acid release from human adipocytes: relation to insulin receptor phosphorylation and intracellular signalling through the insulin receptor substrate-1 pathway[J].Diabetologia, 1998,41(11): 1 343-1 354.
[9] Marchesini G, Brizi M, Bianchi G, et al.Nonalcoholic fatty liver disease:a feature of the metabolic syndrome[J].Diabetes, 2001,50(8): 1 844-1 850.
[10] Czaja M J, Ding W X, Donohue T M, et al.Functions of autophagy in normal and diseased liver[J].Autophagy, 2013,9(8): 1 131-1 158.
[11] Berk P D.Regulatable fatty acid transport mechanisms are central to the pathophysiology of obesity, fatty liver, and metabolic syndrome[J].Hepatology, 2008,48(5): 1 362-1 376.
[12] Ge F, Zhou S, Hu C, et al.Insulin-and leptin-regulated fatty acid uptake plays a key causal role in hepatic steatosis in mice with intact leptin signaling but not in ob/ob or db/db mice[J].American Journal of physiology Gastrointestinal and Liver Physiology, 2010,299(4): G855-G866.
[13] Liu F, Xie M X, Chen D L, et al.Effect of (VO)-O-IV(dipic-Cl)(H2O)(2) on lipid metabolism disorders in the liver of STZ-induced diabetic rats[J].Journal of Diabetes Research, 2013(1): 1-10.
[14] Liang G S, Yang J, Horton J D, et al.Diminished hepatic response to fasting/refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-1c[J].The Journal of Biological Chemistry, 2002,277(11): 9 520-9 528.
[15] Perez-Carreras M, Del Hoyo P, Martin M A, et al.Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis[J].Hepatology, 2003,38(4): 999-1 007.
[16] Xu A, Wang Y, Keshaw H, et al.The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice[J].The Journal of Clinical Investigation, 2003,112(1): 91-100.
[17] Cohen P, Miyazaki M, Socci N D, et al.Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss[J].Science, 2002,297(5 579): 240-243.
[18] Stanhope K L, Schwarz J M, Keim N L, et al.Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans[J].The Journal of Clinical Investigation, 2009,119(5): 1 322-1 334.
[19] Chakravarthy M V, Pan Z J, Zhu Y M, et al."New" hepatic fat activates PPAR alpha to maintain glucose, lipid, and cholesterol homeostasis[J].Cell Metabolism, 2005,1(5): 309-322.
[20] Ding X K, Saxena N K, Lin S B, et al.Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, reverses hepatic steatosis in ob/ob mice[J].Hepatology, 2006,43(1): 173-181.
[21] Wierzbicki M, Chabowski A, Zendzian-Piotrowska M, et al.Differential effects of in vivo PPAR alpha and gamma activation on fatty acid transport proteins expression and lipid content in rat liver[J].Journal of Physiology and Pharmacology, 2009,60(1): 99-106.
[22] Knight B L, Hebbachi A, Hauton D, et al.A role for PPARalpha in the control of SREBP activity and lipid synthesis in the liver[J].Biochemical Journal, 2005,389(Pt 2): 413-421.
[23] Schadinger S E, Bucher N L, Schreiber B M, et al.PPARgamma2 regulates lipogenesis and lipid accumulation in steatotic hepatocytes[J].American Journal of physiology Endocrinology and metabolism, 2005,288(6): E1 195-E1 205.
[24] Samuel V T, Petersen K F, Shulman G I.Lipid-induced insulin resistance: unravelling the mechanism[J].The Lancet, 2010,375(9 733): 2 267-2 277.
[25] Edwards P A, Kast H R, Anisfeld A M.BAREing it all: the adoption of LXR and FXR and their roles in lipid homeostasis[J].Journal of Lipid Research, 2002,43(1): 2-12.
[26] Shimomura I, Matsuda M, Hammer R E, et al.Decreased IRS-2 and increased SREBP-1c lead to mixed insulin resistance and sensitivity in livers of lipodystrophic and ob/ob mice[J].Molecular Cell, 2000,6(1): 77-86.
[27] Uyeda KRepa J J.Carbohydrate response element binding protein, ChREBP, a transcription factor coupling hepatic glucose utilization and lipid synthesis[J].Cell Metabolism, 2006,4(2): 107-110.
[28] Sul H S, Latasa M J, Moon Y, et al.Regulation of the fatty acid synthase promoter by insulin[J].Journal of Nutrition, 2000,130(2S Suppl): 3 15S-3 20S.
[29] Hardie D G.Minireview: the AMP-activated protein kinase cascade: the key sensor of cellular energy status[J].Endocrinology, 2003,144(12): 5 179-5 183.
[30] Kobayashi S.Choose delicately and reuse adequately: the newly revealed process of autophagy[J].Biological & Pharmaceutical Bulletin, 2015,38(8): 1 098-1 103.
[31] Singh RCuervo A M.Autophagy in the cellular energetic balance[J].Cell Metabolism, 2011,13(5): 495-504.
[32] Singh R, Kaushik S, Wang Y J, et al.Autophagy regulates lipid metabolism[J].Nature, 2009,458(7 242): 1 131-1 135.
[33] Rautou P E, Mansouri A, Lebrec D, et al.Autophagy in liver diseases[J].Journal of Hepatology, 2010,53(6): 1 123-1 134.
[34] Yang L, Li P, Fu S N, et al.Defective hepatic autophagy in obesity promotes ER stress and causes insulin resistance[J].Cell Metabolism, 2010,11(6): 467-478.
[35] Mehrpour M, Esclatine A, Beau I, et al.Autophagy in health and disease.1.Regulation and significance of autophagy: an overview[J].American Journal of Physiology-Cell Physiology, 2010,298(4): C776-C785.
[36] Orenstein S JCuervo A M.Chaperone-mediated autophagy: Molecular mechanisms and physiological relevance[J].Seminars in Cell & Developmental Biology, 2010,21(7): 719-726.
[37] Mizushima NLevine B.Autophagy in mammalian development and differentiation[J].Nature Cell Biology, 2010,12(9): 823-830.
[38] Sarbassov D D, Ali S M, Sabatini D M.Growing roles for the mTOR pathway[J].Current Opinion in Cell Biology, 2005,17(6): 596-603.
[39] Liang X H, Jackson S, Seaman M, et al.Induction of autophagy and inhibition of tumorigenesis by beclin 1[J].Nature, 1999,402(6 762): 672-676.
[40] Backer J M.The regulation and function of Class III PI3Ks: novel roles for Vps34[J].Biochemical Journal, 2008,410: 1-17.
[41] Mizushima N, Noda T, Yoshimori T, et al.A protein conjugation system essential for autophagy[J].Nature, 1998,395(6 700): 395-398.
[42] Ohsumi Y, Mizushima N.Two ubiquitin-like conjugation systems essential for autophagy[J].Seminars in Cell & Developmental Biology, 2004,15(2): 231-236.
[43] Ichimura Y, Kirisako T, Takao T, et al.A ubiquitin-like system mediates protein lipidation[J].Nature, 2000,408(6 811): 488-492.
[44] Koga H, Kaushik S, Cuervo A M.Altered lipid content inhibits autophagic vesicular fusion[J].The Journal of the Federation of American Societies for Experimental Biology, 2010,24(8): 3 052-3 065.
[45] Singh R, Kaushik S, Wang Y J, et al.Autophagy regulates lipid metabolism[J].Nature, 2009,458(7 242): 1 131-1 164.
[46] Amir MCzaja M J.Autophagy in nonalcoholic steatohepatitis[J].Expert Review of Gastroenterology & Hepatology, 2011,5(2): 159-166.
[47] Farese R V, Jr.Walther T C.Lipid droplets finally get a little R-E-S-P-E-C-T[J].Cell, 2009,139(5): 855-860.
[48] Shibata M, Yoshimura K, Furuya N, et al.The MAP1-LC3 conjugation system is involved in lipid droplet formation[J].Biochemical and Biophysical Research Communications, 2009,382(2): 419-423.
[49] Czaja M J.Autophagy in health and disease.2.Regulation of lipid metabolism and storage by autophagy: pathophysiological implications[J].American Journal of Physiology-Cell Physiology, 2010,298(5): C973-C978.
[50] Shibata M, Yoshimura K, Furuya N, et al.The MAP1-LC3 conjugation system is involved in lipid droplet formation[J].Biochemical and Biophysical Research Communications, 2009,382(2): 419-423.
[51] Kaushik SCuervo A M.Degradation of lipid droplet-associated proteins by chaperone-mediated autophagy facilitates lipolysis[J].Nature Cell Biology, 2015,17(6): 759-770.
[52] Quan W, Kim H K, Moon E Y, et al.Role of hypothalamic proopiomelanocortin neuron autophagy in the control of appetite and leptin response[J].Endocrinology, 2012,153(4): 1 817-1 826.
[53] Peterson T R, Sengupta S S, Harris T E, et al.mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway[J].Cell, 2011,146(3): 408-420.
[54] Sugatani J, Noguchi Y, Hattori Y, et al.Threonine-408 regulates the stability of human pregnane X receptor through Its phosphorylation and the CHIP/chaperone-autophagy pathway[J].Drug Metabolism and Disposition, 2016,44(1): 137-150.
[55] Egan D F, Shackelford D B, Mihaylova M M, et al.Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy[J].Science, 2011,331(6 016): 456-461.
[56] Liu H Y, Han J M, Cao S Y, et al.Hepatic autophagy is suppressed in the presence of insulin resistance and hyperinsulinemia inhibition of FoxO1-dependent expression of key autophagy genes by insulin[J].The Journal of Biological Chemistry, 2009,284(45): 31 484-31 492.
[57] Seo Y K, Jeon T I, Chong H K, et al.Genome-wide localization of SREBP-2 in hepatic chromatin predicts a role in autophagy[J].Cell Metabolism, 2011,13(4): 367-375.
[58] Lin Z F, Wu F, Lin S Q, et al.Adiponectin protects against acetaminophen-induced mitochondrial dysfunction and acute liver injury by promoting autophagy in mice[J].Journal of Hepatology, 2014,61(4): 825-831.
[59] Lee J M, Wagner M, Xiao R, et al.Nutrient-sensing nuclear receptors coordinate autophagy[J].Nature, 2014,516(7 529): 112-115.
[60] Wang K, Damjanov I, Wan Y J Y.The protective role of pregnane X receptor in lipopolysaccharide/D-galactosamine-induced acute liver injury[J].Laboratory Investigation, 2010,90(2):257-265.
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