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

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.

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Published on 10-13-2008
Authors: Min-Seon Kim1, Joong-Yeol Park1, Cherl Namkoong2, Pil-Geum Jang2, Je-Won Ryu2, Hai-Sun Song2, Ji-Young Yun2, Il-Seong Namgoong1, Joohun Ha3, In-Sun Park4, In-Kyu Lee5, Benoit Viollet6, Jang Hyun Youn7, Hong-Kyu Lee8 & Ki-Up Lee1
Source: Nature Medicine 10, 727 - 733 (2004),