The SCAP/SREBP pathway: A mediator of hepatic steatosis

Endocrinology and Metabolism

Volumn 32, Issue 1, 2017, Pages 6-10

  Moon, Young Ah ^a  

^a Inha University School of Medicine   (South Korea)

Author keywords

Hypertriglyceridemia; Insulin resistance; Lipogenesis; Non alcoholic fatty liver disease

Indexed keywords

CARNITINE PALMITOYLTRANSFERASE I; FATTY ACID; HORMONE SENSITIVE LIPASE; INSULIN; MALONYL COENZYME A; PROTEIN; STEROL REGULATORY ELEMENT BINDING PROTEIN 1C; STEROL REGULATORY ELEMENT BINDING PROTEIN CLEAVAGE ACTIVATING PROTEIN; TRIACYLGLYCEROL; TRIACYLGLYCEROL LIPASE; UNCLASSIFIED DRUG; VERY LOW DENSITY LIPOPROTEIN;

DYSLIPIDEMIA; FATTY LIVER; HUMAN; HYPERINSULINEMIA; HYPERTRIGLYCERIDEMIA; INSULIN RESISTANCE; LIPID LIVER LEVEL; LIPOGENESIS; NONALCOHOLIC FATTY LIVER; NONHUMAN; OBESITY; PROTEIN FUNCTION; REGULATORY MECHANISM; REVIEW;

EID: 85015973538     PISSN: 2093596X     EISSN: 20935978     Source Type: Journal    
DOI: 10.3803/EnM.2017.32.1.6     Document Type: Review

References (19)

1. Clark JM. The epidemiology of nonalcoholic fatty liver disease in adults. J Clin Gastroenterol 2006;40 Suppl 1:S5-10.
2. Lazo M, Clark JM. The epidemiology of nonalcoholic fatty liver disease: a global perspective. Semin Liver Dis 2008;28: 339-50.
3. Starley BQ, Calcagno CJ, Harrison SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology 2010;51:1820-32.
4. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002;346:1221-31.
5. Marchesini G, Brizi M, Bianchi G, Tomassetti S, Bugianesi E, Lenzi M, et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 2001;50:1844-50.
6. Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 2005;115:1343-51.
7. Shimomura I, Bashmakov Y, Horton JD. Increased levels of nuclear SREBP-1c associated with fatty livers in two mouse models of diabetes mellitus. J Biol Chem 1999;274:30028-32.
8. Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 2002;109:1125-31.
9. Ishii S, Iizuka K, Miller BC, Uyeda K. Carbohydrate response element binding protein directly promotes lipogenic enzyme gene transcription. Proc Natl Acad Sci U S A 2004; 101:15597-602.
10. Gavrilova O, Haluzik M, Matsusue K, Cutson JJ, Johnson L, Dietz KR, et al. Liver peroxisome proliferator-activated receptor gamma contributes to hepatic steatosis, triglyceride clearance, and regulation of body fat mass. J Biol Chem 2003;278:34268-76.
11. Yang T, Espenshade PJ, Wright ME, Yabe D, Gong Y, Aebersold R, et al. Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell 2002;110: 489-500.
12. Yabe D, Brown MS, Goldstein JL. Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks ex port of sterol regulatory element-binding proteins. Proc Natl Acad Sci U S A 2002;99:12753-8.
13. Shimano H, Horton JD, Shimomura I, Hammer RE, Brown MS, Goldstein JL. Isoform 1c of sterol regulatory element binding protein is less active than isoform 1a in livers of transgenic mice and in cultured cells. J Clin Invest 1997;99: 846-54.
14. Moon YA, Liang G, Xie X, Frank-Kamenetsky M, Fitzgerald K, Koteliansky V, et al. The Scap/SREBP pathway is essential for developing diabetic fatty liver and carbohydrateinduced hypertriglyceridemia in animals. Cell Metab 2012; 15:240-6.
15. Liang G, Yang J, Horton JD, Hammer RE, Goldstein JL, Brown MS. Diminished hepatic response to fasting/refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-1c. J Biol Chem 2002;277:9520-8.
16. Iizuka K, Bruick RK, Liang G, Horton JD, Uyeda K. Deficiency of carbohydrate response element-binding protein (ChREBP) reduces lipogenesis as well as glycolysis. Proc Natl Acad Sci U S A 2004;101:7281-6.
17. Matsuda M, Korn BS, Hammer RE, Moon YA, Komuro R, Horton JD, et al. SREBP cleavage-activating protein (SCAP) is required for increased lipid synthesis in liver induced by cholesterol deprivation and insulin elevation. Genes Dev 2001;15:1206-16.
18. Bril F, Sninsky JJ, Baca AM, Superko HR, Portillo Sanchez P, Biernacki D, et al. Hepatic steatosis and insulin resistance, but not steatohepatitis, promote atherogenic dyslipidemia in NAFLD. J Clin Endocrinol Metab 2016;101:644-52.
19. Makadia SS, Blaha M, Keenan T, Ndumele C, Jones S, De-Filippis A, et al. Relation of hepatic steatosis to atherogenic dyslipidemia. Am J Cardiol 2013;112:1599-604.