Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase.

Abstract

AMP-activated protein kinase (AMPK) functions as a fuel sensor in the cell and is activated when cellular energy is depleted. Here we report that alpha-lipoic acid (alpha-LA), a cofactor of mitochondrial enzymes, decreases hypothalamic AMPK activity and causes profound weight loss in rodents by reducing food intake and enhancing energy expenditure. Activation of hypothalamic AMPK reverses the effects of alpha-LA on food intake and energy expenditure. Intracerebroventricular (i.c.v.) administration of glucose decreases hypothalamic AMPK activity, whereas inhibition of intracellular glucose utilization through the administration of 2-deoxyglucose increases hypothalamic AMPK activity and food intake. The 2-deoxyglucose-induced hyperphagia is reversed by inhibiting hypothalamic AMPK. Our findings indicate that hypothalamic AMPK is important in the central regulation of food intake and energy expenditure and that alpha-LA exerts anti-obesity effects by suppressing hypothalamic AMPK activity.

• Authors: Min-Seon Kim, Joong-Yeol Park, Cherl Namkoong, Pil-Geum Jang, Je-Won Ryu, Hai-Sun Song, Ji-Young Yun, Il-Seong Namgoong, Joohun Ha, In-Sun Park, In-Kyu Lee, Benoit Viollet, Jang Hyun Youn, Hong-Kyu Lee, Ki-Up Lee
• Journal: Nature medicine (Nat Med) Vol. 10 Issue 7 Pg. 727-33 (Jul 2004) ISSN: 1078-8956 [Print] United States
• PMID: 15195087 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Obesity Agents
• Leptin
• Thioctic Acid
• Cyclic AMP-Dependent Protein Kinases

Topics

• Animals
• Anti-Obesity Agents (pharmacology)
• Body Weight (drug effects)
• Cyclic AMP-Dependent Protein Kinases (antagonists & inhibitors, physiology)
• Eating (drug effects)
• Energy Metabolism (drug effects)
• Enzyme Activation (drug effects)
• Hypothalamus (drug effects, enzymology, physiology)
• Leptin (physiology)
• Mice
• Muscle, Skeletal (drug effects, metabolism)
• Rats
• Thioctic Acid (pharmacology)