Alpha-lipoic acid decreases hepatic lipogenesis through adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways

Keun-Gyu Park, Ae-Kyung Min, Eun Hee Koh, Hyoun Sik Kim, Mi-Ok Kim, Hye-Sun Park, Yong-Deuk Kim, Tae-Seung Yoon, Byoung Kuk Jang, Jae Seok Hwang, Jae Bum Kim, Hueng-Sik Choi, Joong-Yeol Park, In-Kyu Lee, Ki-Up Lee
Hepatology: Official Journal of the American Association for the Study of Liver Diseases 2008, 48 (5): 1477-86

UNLABELLED: Fatty liver is common in obese subjects with insulin resistance. Hepatic expression of sterol regulatory element binding protein-1c (SREBP-1c), which plays a major role in hepatic steatosis, is regulated by multiple factors, including insulin, adenosine monophosphate-activated protein kinase (AMPK), liver X receptors (LXRs), and specificity protein 1. Alpha-lipoic acid (ALA), a naturally occurring antioxidant, has been shown to decrease lipid accumulation in skeletal muscle by activating AMPK. Here we show that ALA decreases hepatic steatosis and SREBP-1c expression in rats on a high fat diet or given an LXR agonist. ALA increased AMPK phosphorylation in the liver and in cultured liver cells, and dominant-negative AMPK partially prevented ALA-induced suppression of insulin-stimulated SREBP-1c expression. ALA also inhibited DNA-binding activity and transcriptional activity of both specificity protein 1 and LXR.

CONCLUSION: These results show that ALA prevents fatty liver disease through multiple mechanisms, and suggest that ALA can be used to prevent the development and progression of nonalcoholic fatty liver disease in patients with insulin resistance.

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