We found a match

Your institution may have access to this item. Find your institution then sign in to continue.

Title

Alpha-Lipoic Acid Prevents Insulin-Induced Hepatic Steatosis Via Down-Regulation of SREBP-1c.

Authors

Park, Keun-Gyu; Min, Ae-Kyung; Kim, Hye-Soon; Cho, Ho-Chan; Kim, Mi-Kyung; Jung, Gui-Hwa; Do, Yoon-Jung; Kim, Sunyee; Ryu, Min-Jeong; Choi, Seoung-Hee; Kim, Jung-Guk; Kim, Bo-Wan; Lee, In-Kyu

Abstract

Non alcoholic fatty liver disease is common in patients with insulin resistance. Sterol regulatory element binding protein-1c (SREBP-1c) is a family of transcription factors that have been established as key regulators for lipid accumulation in the liver by activating the enzymes involved in the fatty acid biosynthetic pathway. We showed previously that alpha-lipoic acid (ALA) activates AMP-activated protein kinase (AMPK) and reduces lipid accumulation in skeletal muscle of obese OLETF rats. Here, we investigated whether ALA inhibits insulin-stimulated SREBP- 1c expression and improves hepatic steatosis by activating AMPK. Insulin markedly increased both SREBP-1c gene expression and active form change of SREBP-1c protein in HepG2 and H4IIE cells. The SREBP-1c gene expression in the liver of OLETF rats was increased compared with that of LETO rats. ALA increased AMPK phosphorylation in hepatocytes and inhibited insulin-stimulated active form change of SREBPI c protein as well as SREBP-1c gene expression. Conseqeuntly, ALA decreased target gene expression of SREBP-1c including fatty acid synthase and acetyl coA carboxylase. Moreover, short-term treatment of ALA decreased SREBP1c expression in the liver of OLETF rats. Dominant negative AMPK reversed the inhibitory effects of ALA on insulin-stimulated SREBP-1c gene expression. Present study shows that ALA has a preventive effect on insulin-induced hepatic steatosis and suggests the possibility that ALA could be used to prevent the development and progression of nonalcoholic fatty liver disease in patients with insulin resistance.

Subjects

LIPOIC acid; FATTY degeneration; FATTY liver; INSULIN; STEROLS; PROTEIN kinases; GENE expression; INSULIN resistance

Publication

Diabetes, 2007, Vol 56, pA390

ISSN

0012-1797

Publication type

Academic Journal