Ghrelin Regulation of AMPK in the Hypothalamus and Peripheral Tissues

Adenosine 5′ monophosphate-activated protein kinase (AMPK) is a regulator of cellular and systemic energy homeostasis. Several appetite-regulating and metabolic hormones are known to influence AMPK. Ghrelin displays central orexigenic as well as direct peripheral metabolic effects and both could be related to its effects on AMPK activity. In the hypothalamus ghrelin stimulates AMPK and this has been associated with its orexigenic effects. Evidence suggests a tight interaction between the central ghrelin and cannabinoid systems, and hypothalamic AMPK appears to be a common mediator of their orexigenic effects. In the liver and adipose tissue, ghrelin inhibits AMPK and this could be the underlying mechanism for its diabetogenic and lipogenic effects. While in cardiac muscle, ghrelin stimulates AMPK which could be linked to its positive inotropic effects. In summary, tissue-specific alterations of AMPK activity play an important role in the diverse effects of ghrelin.