Alcohol
Volume 34, Issue 1 , Pages 39-43 , August 2004

Molecular mechanisms of alcoholic fatty liver: role of sterol regulatory element-binding proteins

Received 30 March 2004 ,Revised 15 July 2004 ,Accepted 20 July 2004.

References 

  1. Arakawa M, Taketomi S, Furuno K, Matsuo T, Iwatsuka H. Metabolic studies on the development of ethanol-induced fatty liver in KK-Ay mice. J Nutr. 1975;105:1500–1508
  2. Bardag-Gorce F, Yuan QX, Li J, French BA, Fang C, Ingelman-Sundberg M, et al. The effect of ethanol-induced cytochrome p4502E1 on the inhibition of proteasome activity by alcohol. Biochem Biophys Res Commun. 2000;279:23–29
  3. Brown MS, Goldstein JL. A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood. Proc Natl Acad Sci U S A. 1999;96:11041–11048
  4. Carrasco MP, Marco C, Segovia JL. Chronic ingestion of ethanol stimulates lipogenic response in rat hepatocytes. Life Sci. 2001;68:1295–1304
  5. Fischer M, You M, Matsumoto M, Crabb DW. Peroxisome proliferator-activated receptor α (PPARα) agonist treatment reverses PPARα dysfunction and abnormalities in hepatic lipid metabolism in ethanol-fed mice. J Biol Chem. 2003;278:27997–28004
  6. Galli A, Price D, Crabb D. High-level expression of rat class I alcohol dehydrogenase is sufficient for ethanol-induced fat accumulation in transduced HeLa cells. Hepatology. 1999;29:1164–1170
  7. Hardie DG, Pan DA. Regulation of fatty acid synthesis and oxidation by the AMP-activated protein kinase. Biochem Soc Trans. 2002;30:1064–1070
  8. Higashi K, Hoshino M, Nomura T, Saso K, Ito M, Hoek JB. Interaction of protein phosphatases and ethanol on phospholipase C–mediated intracellular signal transduction processes in rat hepatocytes: role of protein kinase A. Alcohol Clin Exp Res. 1996;20:320A–324A
  9. 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;109:1125–1131
  10. Ji C, Kaplowitz N. Betaine decreases hyperhomocysteinemia, endoplasmic reticulum stress, and liver injury in alcohol-fed mice. Gastroenterology. 2003;124:1488–1499
  11. Joly J-G, Feinman L, Ishii H, Lieber CS. Effect of chronic ethanol feeding on hepatic microsomal glycerophosphate acyltransferase activity. J Lipid Res. 1973;14:337–343
  12. Kovacic S, Soltys C-LM, Barr AJ, Shiojima I, Walsh K, Dyck JRB. Akt activity negatively regulates phosphorylation of AMP-activated protein kinase in the heart. J Biol Chem. 2003;278:39422–39427
  13. Lieber CS, Spritz N, DeCarli LM. Role of dietary, adipose, and endogenously synthesized fatty acids in the pathogenesis of the alcoholic fatty liver. J Clin Invest. 1966;45:51–62
  14. Lin HZ, Yang SQ, Chuckaree C, Kuhajda F, Ronnet G, Diehl AM. Metformin reverses fatty liver disease in obese, leptin-deficient mice. Nat Med. 2000;6:998–1003
  15. Lluis JM, Colell A, García-Ruiz C, Kaplowitz N, Fernández-Checa JC. Acetaldehyde impairs mitochondrial glutathione transport in HepG2 cells through endoplasmic reticulum stress. Gastroenterology. 2003;124:708–724
  16. Muramatsu M, Kuriyama K, Yuki T, Ohkuma S. Hepatic lipogenesis and mobilization of peripheral fats in the formation of alcoholic fatty liver. Jpn J Pharmacol. 1981;31:931–940
  17. Ouchi N, Kobayashi H, Kihara S, Kumada M, Sato K, Inoue T, et al. Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells. J Biol Chem. 2004;279:1304–1309
  18. Repa JJ, Liang G, Ou J, Bashmakov Y, Lobaccaro J-MA, Shimomura I, et al. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRα and LXRβ. Genes Dev. 2000;14:2819–2830
  19. Sakai J, Rawson RB, Espenshade PJ, Cheng D, Seegmiller AC, Goldstein JL, et al. Molecular identification of the sterol-regulated luminal protease that cleaves SREBPs and controls lipid composition of animal cells. Mol Cell. 1998;2:505–514
  20. Seitz HK, Kuhn B, von Hodenberg E, Fiehn W, Conradt C, Simanowski UA. Increased messenger RNA levels for low-density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase in rat liver after long-term ethanol ingestion. Hepatology. 1994;20:487–493
  21. Shimano H, Horton JD, Hammer RE, Shimomura I, Brown MS, Goldstein JL. Overproduction of cholesterol and fatty acids causes massive liver enlargement in transgenic mice expressing truncated SREBP-1a. J Clin Invest. 1996;98:1575–1584
  22. 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;274:30028–30032
  23. Shimomura I, Hammer RE, Ikemoto S, Brown MS, Goldstein JL. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature. 1999;401:73–76
  24. Shimomura I, Matsuda M, Hammer RE, Bashmakov Y, Brown MS, Goldstein JL. Decreased IRS-2 and increased SREBP-1c lead to mixed insulin resistance and sensitivity in livers of lipodystrophic and ob/ob mice. Mol Cell. 2000;6:77–86
  25. Shimomura I, Shimano H, Horton JD, Goldstein JL, Brown MS. Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells. J Clin Invest. 1997;99:838–845
  26. Shklyaev S, Aslanidi G, Tennant M, Prima V, Kohlbrenner E, Kroutov V, et al. Sustained peripheral expression of transgene adiponectin offsets the development of diet-induced obesity in rats. Proc Natl Acad Sci U S A. 2003;100:14217–14222
  27. Siler SQ, Neese RA, Hellerstein MK. De novo lipogenesis, lipid kinetics, and whole-body lipid balances in humans after acute alcohol consumption. Am J Clin Nutr. 1999;70:928–936
  28. Winder WW, Hardie DG. AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. Am J Physiol. 1999;277:E1–E10
  29. Xu A, Wang Y, Keshaw H, Xu LY, Lam KSL, Cooper GJS. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J Clin Invest. 2003;112:91–100
  30. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med. 2002;8:1288–1295
  31. Yeon JE, Califano S, Xu J, Wands JR, De La Monte SM. Potential role of PTEN phosphatase in ethanol-impaired survival signaling in the liver. Hepatology. 2003;38:703–714
  32. You M, Fischer M, Deeg MA, Crabb DW. Ethanol induces fatty acid synthesis pathways by activation of sterol regulatory element-binding protein (SREBP). J Biol Chem. 2002;277:29342–29347
  33. You, M., Matsumoto, M., Pacold, C. M., Cho, W. K., & Crabb, D. W. (In press). The role of AMP-activated protein kinase in the action of ethanol in the liver. Gastroenterology.
  34. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001;108:1167–1174
  35. Zhou H-Z, Karliner JS, Gray MO. Moderate alcohol consumption induces sustained cardiac protection by activating PKC-εand Akt. Am J Physiol Heart Circ Physiol. 2002;283:H165–H174
  36. Zou M-H, Hou X-Y, Shi C-M, Nagata D, Walsh K, Cohen RA. Modulation by peroxynitrite of Akt- and AMP-activated kinase-dependent Ser1179 phosphorylation of endothelial nitric oxide synthase. J Biol Chem. 2002;277:32552–32557

PII: S0741-8329(04)00152-1

doi: 10.1016/j.alcohol.2004.07.004

Alcohol
Volume 34, Issue 1 , Pages 39-43 , August 2004

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