Pharmacological cholesterol lowering reverses fibrotic NASH in obese, diabetic mice with metabolic syndrome

Journal of Hepatology

Volumn 59, Issue 1, 2013, Pages 144-152

  Van Rooyen, Derrick M ^a   Gan, Lay T ^a   Yeh, Matthew M ^b   Haigh, W Geoffrey ^c   Larter, Claire Z ^a   Ioannou, George ^c   Teoh, Narci C ^a   Farrell, Geoffrey C ^a  

^a CANBERRA HOSPITAL   (Australia)

^b UNIVERSITY OF WASHINGTON MEDICAL CENTER   (United States)

^c UNIVERSITY OF WASHINGTON   (United States)

Author keywords

Atorvastatin; Ezetimibe; Inflammatory recruitment; Lipotoxicity; Liver fibrosis

Indexed keywords

ALANINE AMINOTRANSFERASE; ATORVASTATIN; EZETIMIBE; MESSENGER RNA; MONOCYTE CHEMOTACTIC PROTEIN 1; MYELOPEROXIDASE; STRESS ACTIVATED PROTEIN KINASE;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; CONTROLLED STUDY; DIABETES MELLITUS; ENZYME ACTIVATION; FEMALE; HEPATITIS; HYPERINSULINEMIA; IMMUNOHISTOCHEMISTRY; LIPID ANALYSIS; LIVER CELL DAMAGE; LIVER FIBROSIS; LIVER HISTOLOGY; MACROPHAGE; METABOLIC SYNDROME X; MORPHOMETRICS; MOUSE; NONALCOHOLIC FATTY LIVER; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; STEATOSIS;

ADIPONECTIN; ANIMALS; ANTICHOLESTEREMIC AGENTS; AZETIDINES; CHOLESTEROL; DIABETES COMPLICATIONS; DRUG THERAPY, COMBINATION; FATTY LIVER; FEMALE; HEPTANOIC ACIDS; INSULIN; LIVER; MAP KINASE SIGNALING SYSTEM; METABOLIC SYNDROME X; MICE; MICE, MUTANT STRAINS; MICE, OBESE; PYRROLES;

EID: 84879132692     PISSN: 01688278     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jhep.2013.02.024     Document Type: Article

References (30)

1. K. Cusi Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications Gastroenterology 142 2012 e716
2. C.Z. Larter, S. Chitturi, D. Heydet, and G.C. Farrell A fresh look at NASH pathogenesis. Part 1: The metabolic movers J Gastroenterol Hepatol 25 2010 672 690
3. G.C. Farrell, D. van Rooyen, L. Gan, and S. Chitturi NASH is an inflammatory disorder: pathogenic, prognostic and therapeutic implications Gut Liver 6 2012 149 171
4. B.A. Neuschwander-Tetri Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: the central role of nontriglyceride fatty acid metabolites Hepatology 52 2010 774 788
5. K. Kakisaka, S.C. Cazanave, C.D. Fingas, M.E. Guicciardi, S.F. Bronk, and N.W. Werneburg Mechanisms of lysophosphatidylcholine-induced hepatocyte lipoapoptosis Am J Physiol Gastrointest Liver Physiol 302 2012 G77 G84
6. S. Mei, H.M. Ni, S. Manley, A. Bockus, K.M. Kassel, and J.P. Luyendyk Differential roles of unsaturated and saturated fatty acids on autophagy and apoptosis in hepatocytes J Pharmacol Exp Ther 339 2011 487 498
7. C.Z. Larter, M.M. Yeh, W.G. Haigh, J. Williams, S. Brown, and K.S. Bell-Anderson Hepatic free fatty acids accumulate in experimental steatohepatitis: role of adaptive pathways J Hepatol 48 2008 638 647
8. P. Puri, R.A. Baillie, M.M. Wiest, F. Mirshahi, J. Choudhury, and O. Cheung A lipidomic analysis of nonalcoholic fatty liver disease Hepatology 46 2007 1081 1090
9. F. Caballero, A. Fernandez, A.M. De Lacy, J.C. Fernandez-Checa, J. Caballeria, and C. Garcia-Ruiz Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH J Hepatol 50 2009 789 796
10. H.K. Min, A. Kapoor, M. Fuchs, F. Mirshahi, H. Zhou, and J. Maher Increased hepatic synthesis and dysregulation of cholesterol metabolism is associated with the severity of nonalcoholic fatty liver disease Cell Metab 15 2012 665 674
11. G.C. Farrell, and D. van Rooyen Liver cholesterol: is it playing possum in NASH? Am J Physiol Gastrointest Liver Physiol 303 2012 G9 G11
12. D.M. Van Rooyen, C.Z. Larter, W.G. Haigh, M.M. Yeh, G. Ioannou, and R. Kuver Hepatic free cholesterol accumulates in obese, diabetic mice and causes nonalcoholic steatohepatitis Gastroenterology 141 2011 1393 1403 e1391-e1395
13. M. Mari, F. Caballero, A. Colell, A. Morales, J. Caballeria, and A. Fernandez Mitochondrial free cholesterol loading sensitizes to TNF- and Fas-mediated steatohepatitis Cell Metab 4 2006 185 198
14. K. Wouters, P.J. van Gorp, V. Bieghs, M.J. Gijbels, H. Duimel, and D. Lutjohann Dietary cholesterol, rather than liver steatosis, leads to hepatic inflammation in hyperlipidemic mouse models of nonalcoholic steatohepatitis Hepatology 48 2008 474 486
15. J. Chan, M.C. Mahaney, R.S. Kushwaha, J.F. VandeBerg, and J.L. VandeBerg ABCB4 mediates diet-induced hypercholesterolemia in laboratory opossums J Lipid Res 51 2010 2922 2928
16. D. Heydet, L.X. Chen, C.Z. Larter, C. Inglis, M.A. Silverman, and G.C. Farrell A truncating mutation of Alms1 reduces the number of hypothalamic neuronal cilia in obese mice Dev Neurobiol 73 2013 1 13
17. C.Z. Larter, M.M. Yeh, D.M. Van Rooyen, N.C. Teoh, J. Brooling, and J.Y. Hou Roles of adipose restriction and metabolic factors in progression of steatosis to steatohepatitis in obese, diabetic mice J Gastroenterol Hepatol 24 2009 1658 1668
18. D.E. Kleiner, E.M. Brunt, M. Van Natta, C. Behling, M.J. Contos, and O.W. Cummings Design and validation of a histological scoring system for nonalcoholic fatty liver disease Hepatology 41 2005 1313 1321
19. M. Yoneda, K. Fujita, Y. Nozaki, H. Endo, H. Takahashi, and K. Hosono Efficacy of ezetimibe for the treatment of non-alcoholic steatohepatitis: an open-label, pilot study Hepatol Res 40 2010 613 621
20. H. Park, T. Shima, K. Yamaguchi, H. Mitsuyoshi, M. Minami, and K. Yasui Efficacy of long-term ezetimibe therapy in patients with nonalcoholic fatty liver disease J Gastroenterol 46 2011 101 107
21. S. Zheng, L. Hoos, J. Cook, G. Tetzloff, H. Davis Jr., and M. van Heek Ezetimibe improves high fat and cholesterol diet-induced non-alcoholic fatty liver disease in mice Eur J Pharmacol 584 2008 118 124
22. T. Ogawa, H. Fujii, K. Yoshizato, and N. Kawada A human-type nonalcoholic steatohepatitis model with advanced fibrosis in rabbits Am J Pathol 177 2010 153 165
23. H.H. Wang, P. Portincasa, N. Mendez-Sanchez, M. Uribe, and D.Q. Wang Effect of ezetimibe on the prevention and dissolution of cholesterol gallstones Gastroenterology 134 2008 2101 2110
24. J.M. Holub, K. O'Toole-Colin, A. Getzel, A. Argenti, M.A. Evans, and D.C. Smith Lipid-lowering effects of ethyl 2-phenacyl-3-aryl-1H-pyrrole-4- carboxylates in rodents Molecules 9 2004 134 157
25. J.A. Wang, W.A. Chen, Y. Wang, S. Zhang, H. Bi, and B. Hong Statins exert differential effects on angiotensin II-induced atherosclerosis, but no benefit for abdominal aortic aneurysms Atherosclerosis 217 2011 90 96
26. M. Kozuki, T. Kurata, K. Miyazaki, N. Morimoto, Y. Ohta, and Y. Ikeda Atorvastatin and pitavastatin protect cerebellar Purkinje cells in AD model mice and preserve the cytokines MCP-1 and TNF-alpha Brain Res 1388 2011 32 38
27. J. Farkas, A. Angel, and M.I. Avigan Studies on the compartmentation of lipid in adipose cells. II. Cholesterol accumulation and distribution in adipose tissue components J Lipid Res 14 1973 344 356
28. J.M. Schattenberg, R. Singh, Y. Wang, J.H. Lefkowitch, R.M. Rigoli, and P.E. Scherer JNK1 but not JNK2 promotes the development of steatohepatitis in mice Hepatology 43 2006 163 172
29. G. Musso, M. Cassader, and R. Gambino Cholesterol-lowering therapy for the treatment of nonalcoholic fatty liver disease: an update Curr Opin Lipidol 22 2011 489 496
30. M. Ekstedt, L.E. Franzen, U.L. Mathiesen, M. Holmqvist, G. Bodemar, and S. Kechagias Statins in non-alcoholic fatty liver disease and chronically elevated liver enzymes: a histopathological follow-up study J Hepatol 47 2007 135 141