title: 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.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, 138-736 Poongnap-dong, Songpa-ku, Seoul 138-736, Korea.
authors.forename: Min-Seon
authors.initials: MS
authors.lastname: Kim
authors.forename: Joong-Yeol
authors.initials: JY
authors.lastname: Park
authors.forename: Cherl
authors.initials: C
authors.lastname: Namkoong
authors.forename: Pil-Geum
authors.initials: PG
authors.lastname: Jang
authors.forename: Je-Won
authors.initials: JW
authors.lastname: Ryu
authors.forename: Hai-Sun
authors.initials: HS
authors.lastname: Song
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Yun
authors.forename: Il-Seong
authors.initials: IS
authors.lastname: Namgoong
authors.forename: Joohun
authors.initials: J
authors.lastname: Ha
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Park
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Lee
authors.forename: Benoit
authors.initials: B
authors.lastname: Viollet
authors.forename: Jang Hyun
authors.initials: JH
authors.lastname: Youn
authors.forename: Hong-Kyu
authors.initials: HK
authors.lastname: Lee
authors.forename: Ki-Up
authors.initials: KU
authors.lastname: Lee
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D020738:Leptin / Q000502:physiology; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D019440:Anti-Obesity Agents; D020738:Leptin; D008063:Thioctic Acid; D017868:Cyclic AMP-Dependent Protein Kinases