title: Carbenoxolone prevents the development of fatty liver in C57BL/6-Lep ob/ob mice via the inhibition of sterol regulatory element binding protein-1c activity and apoptosis.
abstract: Carbenoxolone is the 3-hemisuccinate of glycyrrhetinic acid, the active principal of licorice (Glycyrrhiza glabra). It was reported that carbenoxolone improved glucose tolerance with increased insulin sensitivity in mice with high fat diet-induced obesity. In the present study, we elucidated the protective effect of carbenoxolone in fatty liver animal models of C57BL/6-Lep(ob/ob) mice through inhibition of hepatic lipogenesis and apoptosis. In addition, the potential mechanisms by which carbenoxolone could exert such protection were elucidated. Carbenoxolone was daily administrated by gavage for 28 days in C57BL/6 and C57BL/6-Lep(ob/ob) mice. Carbenoxolone prevented the plasma triglyceride and free fatty acid accumulation associated with the reduction of the expression of sterol regulatory element binding protein-1c, liver X receptor, fatty acid synthase and acethyl-CoA carboxylase in the livers of C57BL/6-Lep(ob/ob) mice. Carbenoxolone also prevented hepatic injury through anti-apoptotic action in the livers of C57BL/6-Lep(ob/ob) mice, accompanied by increased Bcl-2 expression and suppressed Bax and cytochrome c expression. As a mechanism, increased inflammatory cytokine expressions were inhibited by carbenoxolone in the fatty livers of C57BL/6-Lep(ob/ob) mice. Furthermore, carbenoxolone inhibited free fatty acid (oleate/palmitate) induced reactive oxygen species formation and reversed free fatty acid induced mitochondrial membrane depolarization in HepG2 cells. Carbenoxolone prevents the development of fatty liver by inhibiting sterol regulatory element binding protein-1c expression and activity with an anti-apoptotic mechanism via the inhibition of inflammatory cytokine and reactive oxygen species formation in the livers of C57BL/6-Lep(ob/ob) mice. It is suggested that carbenoxolone prevents the development and progression of fatty liver disease in patients with insulin resistance.
authors: Bio-Organic Science Division, Korea Research Institute of Chemical Technology, PO Box 107, Yuseong-gu, Daejeon, 305-600, Korea.
authors: Sang Dal
authors: SD
authors: Rhee
authors: Chi-Hyun
authors: CH
authors: Kim
authors: Ji Seon
authors: JS
authors: Park
authors: Won Hoon
authors: WH
authors: Jung
authors: Sung Bum
authors: SB
authors: Park
authors: Hee Youn
authors: HY
authors: Kim
authors: Gyu Hwan
authors: GH
authors: Bae
authors: Ta Jan
authors: TJ
authors: Kim
authors: Ki Young
authors: KY
authors: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002229:Carbenoxolone / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D050155:Lipogenesis / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D017382:Reactive Oxygen Species / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D016207:Cytokines; D004791:Enzyme Inhibitors; D005230:Fatty Acids, Nonesterified; D017382:Reactive Oxygen Species; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D002229:Carbenoxolone