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.
Kim
Min-Seon
MS
Department of Internal Medicine, University of Ulsan College of Medicine, 138-736 Poongnap-dong, Songpa-ku, Seoul 138-736, Korea.
Park
Joong-Yeol
JY
Namkoong
Cherl
C
Jang
Pil-Geum
PG
Ryu
Je-Won
JW
Song
Hai-Sun
HS
Yun
Ji-Young
JY
Namgoong
Il-Seong
IS
Ha
Joohun
J
Park
In-Sun
IS
Lee
In-Kyu
IK
Viollet
Benoit
B
Youn
Jang Hyun
JH
Lee
Hong-Kyu
HK
Lee
Ki-Up
KU
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*
D019440:Anti-Obesity Agents; D020738:Leptin; D008063:Thioctic Acid; D017868:Cyclic AMP-Dependent Protein Kinases