title: Mechanisms of intrahepatic triglyceride accumulation.
abstract: Hepatic steatosis defined as lipid accumulation in hepatocytes is very frequently found in adults and obese adolescents in the Western World. Etiologically, obesity and associated insulin resistance or excess alcohol intake are the most frequent causes of hepatic steatosis. However, steatosis also often occurs with chronic hepatitis C virus (HCV) infection and is also found in rare but potentially life-threatening liver diseases of pregnancy. Clinical significance and outcome of hepatic triglyceride accumulation are highly dependent on etiology and histological pattern of steatosis. This review summarizes current concepts of pathophysiology of common causes of hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease, chronic HCV infections, drug-induced forms of hepatic steatosis, and acute fatty liver of pregnancy. Regarding the pathophysiology of NAFLD, this work focuses on the close correlation between insulin resistance and hepatic triglyceride accumulation, highlighting the potential harmful effects of systemic insulin resistance on hepatic metabolism of fatty acids on the one side and the role of lipid intermediates on insulin signalling on the other side. Current studies on lipid droplet morphogenesis have identified novel candidate proteins and enzymes in NAFLD.
authors.affiliation: Claudia Ress, Susanne Kaser, Department of Internal Medicine I, Medical University Innsbruck, 6020 Innsbruck, Austria.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ress
authors.affiliation: Claudia Ress, Susanne Kaser, Department of Internal Medicine I, Medical University Innsbruck, 6020 Innsbruck, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Kaser
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000378:metabolism; D005234:Fatty Liver / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D019698:Hepatitis C, Chronic / Q000453:epidemiology / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology / Q000378:metabolism; D011379:Prognosis; D012307:Risk Factors; D015398:Signal Transduction; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D014280:Triglycerides
keywords: Fatty acids; Insulin resistance; Lipid accumulation; Steatosis; Triglycerides
references.citation: Nat Med. 2013 Jun;19(6):722-9
references.pmid: 23708292
references.citation: J Virol. 2014 Apr;88(8):4195-203
references.pmid: 24478438
references.citation: Gastroenterology. 2012 Jun;142(7):1444-6.e2
references.pmid: 22425588
references.citation: Clin Chem Lab Med. 2009;47(10):1217-25
references.pmid: 19803812
references.citation: Proc Natl Acad Sci U S A. 2014 Aug 5;111(31):11437-42
references.pmid: 25028495
references.citation: Rev Recent Clin Trials. 2014;9(3):204-9
references.pmid: 25514907
references.citation: Am J Physiol Regul Integr Comp Physiol. 2012 Apr 15;302(8):R996-1003
references.pmid: 22378776
references.citation: J Clin Endocrinol Metab. 2005 Mar;90(3):1446-52
references.pmid: 15613417
references.citation: J Hepatol. 2015 Jun;62(6):1375-81
references.pmid: 25543082
references.citation: Clin Sci (Lond). 2011 Mar;120(6):239-50
references.pmid: 20929443
references.citation: Hepatology. 2009 Oct;50(4):1030-7
references.pmid: 19787818
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12587-94
references.pmid: 17640906
references.citation: Biochem J. 2004 Mar 15;378(Pt 3):983-90
references.pmid: 14641110
references.citation: Hepatology. 2015 Sep;62(3):964-7
references.pmid: 25854913
references.citation: Am J Physiol Gastrointest Liver Physiol. 2008 Dec;295(6):G1173-81
references.pmid: 18832448
references.citation: Alcohol Clin Exp Res. 1998 May;22(3 Suppl):164S-169S
references.pmid: 9622397
references.citation: Endocrinology. 2003 Dec;144(12):5179-83
references.pmid: 12960015
references.citation: J Hepatol. 1998 Aug;29(2):198-206
references.pmid: 9722200
references.citation: Diabetologia. 2010 May;53(5):882-9
references.pmid: 20099057
references.citation: J Clin Invest. 2005 May;115(5):1343-51
references.pmid: 15864352
references.citation: J Biol Chem. 2008 Aug 8;283(32):22186-92
references.pmid: 18524776
references.citation: Obes Surg. 2009 May;19(5):608-16
references.pmid: 19301078
references.citation: Diabetes. 2015 Feb;64(2):418-26
references.pmid: 25614670
references.citation: Gastroenterology. 2007 May;132(5):1947-54
references.pmid: 17484887
references.citation: J Hepatol. 2015 Feb;62(2):278-85
references.pmid: 25220251
references.citation: PLoS One. 2014;9(5):e97118
references.pmid: 24831094
references.citation: Hepatology. 2013 May;57(5):1697-704
references.pmid: 23417775
references.citation: J Biol Chem. 2007 Jan 12;282(2):826-30
references.pmid: 17071619
references.citation: Int J Clin Pract. 2010 Jun;64(7):968-83
references.pmid: 20584230
references.citation: J Gastroenterol Hepatol. 2011 Jul;26(7):1089-105
references.pmid: 21545524
references.citation: J Genet Genomics. 2014 May 20;41(5):251-9
references.pmid: 24894352
references.citation: JAMA. 2002 Nov 6;288(17):2163-6
references.pmid: 12413376
references.citation: Annu Rev Nutr. 2001;21:193-230
references.pmid: 11375435
references.citation: Nature. 2009 Apr 30;458(7242):1131-5
references.pmid: 19339967
references.citation: Gut. 1997 Dec;41(6):845-50
references.pmid: 9462221
references.citation: Diabetologia. 2011 Jul;54(7):1596-607
references.pmid: 21468641
references.citation: Hepatology. 2010 Jan;51(1):191-200
references.pmid: 20034024
references.citation: J Hepatol. 2005;42 Suppl(1):S2-12
references.pmid: 15777569
references.citation: Gastroenterology. 2014 Mar;146(3):801-11
references.pmid: 24262277
references.citation: J Pharmacol Exp Ther. 2004 Jul;310(1):417-24
references.pmid: 15016835
references.citation: N Engl J Med. 1999 Jun 3;340(22):1723-31
references.pmid: 10352164
references.citation: Chem Rev. 2011 Oct 12;111(10):6359-86
references.pmid: 21627334
references.citation: J Clin Invest. 2003 Jul;112(1):91-100
references.pmid: 12840063
references.citation: J Biol Chem. 2004 Jul 30;279(31):32345-53
references.pmid: 15166226
references.citation: Gastroenterology. 2001 Sep;121(3):710-23
references.pmid: 11522755
references.citation: PLoS One. 2010;5(12):e14258
references.pmid: 21170385
references.citation: Mol Metab. 2015 Feb 09;4(4):353-7
references.pmid: 25830098
references.citation: Hepatology. 2011 Jan;53(1):116-26
references.pmid: 20967758
references.citation: Hepatology. 2012 Dec;56(6):2154-62
references.pmid: 22707181
references.citation: Cell. 2010 Mar 19;140(6):900-17
references.pmid: 20303879
references.citation: J Hepatol. 2013 Apr;58(4):824-6
references.pmid: 23298629
references.citation: Semin Liver Dis. 1988 Feb;8(1):12-25
references.pmid: 3283941
references.citation: J Viral Hepat. 2014 Jan;21(1):9-18
references.pmid: 24329853
references.citation: Diabetes. 2012 Nov;61(11):2711-7
references.pmid: 22829450
references.citation: Hepatology. 2015 Jun;61(6):1896-907
references.pmid: 25565581
references.citation: Gastroenterology. 2006 May;130(6):1636-42
references.pmid: 16697727
references.citation: J Clin Invest. 2007 Mar;117(3):739-45
references.pmid: 17318260
references.citation: Diabetes. 2014 Nov;63(11):3637-46
references.pmid: 24947350
references.citation: J Hepatol. 2009 Oct;51(4):655-66
references.pmid: 19665246
references.citation: Aliment Pharmacol Ther. 2003 Aug 15;18(4):357-73
references.pmid: 12940921
references.citation: Alcohol Clin Exp Res. 2014 Jun;38(6):1520-31
references.pmid: 24773203
references.citation: Hepatology. 2015 Mar;61(3):870-82
references.pmid: 25179419
references.citation: J Gastrointestin Liver Dis. 2014 Sep;23(3):311-9
references.pmid: 25267960
references.citation: J Hepatol. 2008;48 Suppl 1:S104-12
references.pmid: 18304679
references.citation: Hepatology. 2006 Oct;44(4):865-73
references.pmid: 17006923
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11285-90
references.pmid: 13679577
references.citation: Metabolism. 2015 Feb;64(2):163-71
references.pmid: 25441706
references.citation: J Clin Exp Hepatol. 2014 Jun;4(2):151-62
references.pmid: 25755551
references.citation: Arch Virol. 2014 May;159(5):1017-25
references.pmid: 24240483
references.citation: Gastroenterology. 2005 Feb;128(2):334-42
references.pmid: 15685545
references.citation: Hepatology. 2004 Dec;40(6):1387-95
references.pmid: 15565570
references.citation: Cell. 2015 Feb 12;160(4):745-58
references.pmid: 25662011
references.citation: J Virol. 2010 Jun;84(12):5936-46
references.pmid: 20357092
references.citation: Trends Endocrinol Metab. 2008 Dec;19(10):371-9
references.pmid: 18929493
references.citation: Hepatology. 2014 Jan;59(1):98-108
references.pmid: 23897856
references.citation: Int J Mol Sci. 2014;15(5):8713-42
references.pmid: 24837835
references.citation: Hepatology. 2001 Jun;33(6):1358-64
references.pmid: 11391523
references.citation: J Clin Invest. 2008 Feb;118(2):683-94
references.pmid: 18188449
references.citation: Trends Mol Med. 2015 Jan;21(1):34-42
references.pmid: 25496657
references.citation: Gut. 2008 Jan;57(1):83
references.pmid: 18094203
references.citation: Gut. 2008 Jul;57(7):951-6
references.pmid: 18332072
references.citation: World J Gastroenterol. 2014 Oct 28;20(40):14652-9
references.pmid: 25356028
references.citation: J Lipid Res. 1993 Jul;34(7):1237-44
references.pmid: 8371070
references.citation: Nat Genet. 2008 Dec;40(12):1461-5
references.pmid: 18820647
references.citation: Hepatology. 2007 Aug;46(2):380-7
references.pmid: 17659580
references.citation: Proc Natl Acad Sci U S A. 2012 May 22;109(21):8236-40
references.pmid: 22547801
references.citation: Hepatol Res. 2008;38(11):1122-9
references.pmid: 18684130
references.citation: Nat Med. 2004 Apr;10(4):355-61
references.pmid: 15057233
references.citation: J Biol Chem. 2002 Aug 9;277(32):29342-7
references.pmid: 12036955
references.citation: Hepatology. 2006 Dec;44(6):1648-55
references.pmid: 17133473
references.citation: Gastroenterology. 1998 Apr;114(4):842-5
references.pmid: 9547102
references.citation: Curr Mol Med. 2003 Sep;3(6):561-72
references.pmid: 14527087
references.citation: J Biol Chem. 2008 Oct 10;283(41):27565-74
references.pmid: 18662986
references.citation: Int J Obes Relat Metab Disord. 1996 Feb;20(2):130-6
references.pmid: 8646249
references.citation: World J Gastroenterol. 2015 May 7;21(17):5183-90
references.pmid: 25954092
references.citation: J Virol. 2014 Aug;88(15):8361-74
references.pmid: 24829353
references.citation: Histopathology. 2006 Nov;49(5):450-65
references.pmid: 17064291
references.citation: Cell Metab. 2015 May 5;21(5):739-46
references.pmid: 25955209
references.citation: J Lipid Res. 2012 Sep;53(9):1877-89
references.pmid: 22661308
references.citation: J Biol Chem. 2001 Jan 5;276(1):68-75
references.pmid: 11022051
references.citation: Biol Chem. 2012 Mar;393(3):161-7
references.pmid: 22718631
references.citation: Semin Liver Dis. 2004 Aug;24(3):217-32
references.pmid: 15349801
references.citation: Gut. 2011 Jul;60(7):985-91
references.pmid: 21339203
references.citation: Hepatology. 2012 Feb;55(2):437-46
references.pmid: 21953514
references.citation: Obesity (Silver Spring). 2009 Oct;17(10):1872-7
references.pmid: 19629053
references.citation: J Viral Hepat. 2015 Apr;22(4):376-83
references.pmid: 25219291
references.citation: World J Gastroenterol. 2015 Feb 14;21(6):1927-31
references.pmid: 25684961
references.citation: Semin Liver Dis. 2014 May;34(2):205-14
references.pmid: 24879984
references.citation: J Clin Invest. 2004 Jul;114(2):147-52
references.pmid: 15254578
references.citation: Adv Pharmacol. 1997;38:601-28
references.pmid: 8895826
references.citation: J Hepatol. 2015 Mar;62(3):647-56
references.pmid: 25457208
references.citation: Hepatology. 2005 Apr;41(4):753-60
references.pmid: 15791619
references.citation: J Biol Chem. 2011 Jun 24;286(25):22227-34
references.pmid: 21540183
references.citation: J Clin Invest. 2003 Jan;111(2):197-208
references.pmid: 12531875
references.citation: Hepatology. 2015 Mar;61(3):751-3
references.pmid: 25420909
references.citation: Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):16381-5
references.pmid: 21930939
references.citation: Liver Transpl Surg. 1997 May;3(3):206-11
references.pmid: 9346741
references.citation: J Hepatol. 2015 Apr;62(1 Suppl):S47-64
references.pmid: 25920090
references.citation: Gut. 2005 Jul;54(7):1003-8
references.pmid: 15951550
references.citation: Curr Drug Targets. 2015;16(12):1274-80
references.pmid: 26028042
references.citation: J Clin Invest. 2002 May;109(10):1345-50
references.pmid: 12021250