Role of hypothalamic 5'-AMP-activated protein kinase in the regulation of food intake and energy homeostasis.

Although obesity is an epidemic threat to general health worldwide, an effective treatment has yet to be found. Insights into weight-regulatory pathways will accelerate the identification of new molecular targets for anti-obesity agents. 5'-AMP-activated protein kinase (AMPK) is an enzyme activated during low cellular energy charge. In peripheral tissues, the activation of AMPK influences various metabolic pathways, including glucose uptake, glycolysis, and fatty acid oxidation, all of which help to re-establish a normal cellular energy balance. AMPK is also present in the neurons of the hypothalamus, a critical center in the regulation of energy homeostasis. Recent studies from our group and others have shown that many factors (alpha-lipoic acid, leptin, insulin, ghrelin, glucose, 2-deoxyglucose, etc.) cause an alteration in hypothalamic AMPK activity that mediates effects on feeding behavior. Hypothalamic AMPK also appears to play a role in the central regulation of energy expenditure and peripheral glucose metabolism. These data indicate that hypothalamic AMPK is an important signaling molecule that integrates nutritional and hormonal signals and modulates feeding behavior and energy metabolism.