Appetite and metabolic effects of ghrelin and cannabinoids: involvement of AMP-activated protein kinase.

Obesity is one of the most important health threats to the Western world, and the physiology of appetite-regulating hormones has become a major interest in the last decades. One of the orexigenic hormones, ghrelin is the stomach-derived "brain-gut" peptide, which stimulates energy consumption and storage. Ghrelin promotes gluconeogenesis and adipose tissue deposition. Endocannabinoids, such as anandamide and 2-arachydoglycerol, are lipid-like neurotransmitter molecules activating the cannabinoid receptors. Endocannabinoids, apart from the well-known psychological effects, cause an increase in appetite, and they peripherally promote de novo fatty acid synthesis and gluconeogenesis. Adenosine monophosphate-activated protein kinase (AMPK) is an energy-sensing kinase, which responds to changes in the energy levels of the cell and the whole body in order to maintain adequate ATP levels in the cell. Recently, several hormones have been shown to regulate AMPK activity, and interestingly in a strictly tissue-specific manner. Orexigenic agents such as ghrelin and cannabinoids stimulate hypothalamic AMPK leading to increase in appetite while inhibiting AMPK activity in the liver and adipose tissue, therefore leading to lipogenic and diabetogenic effects. Here we summarize the recent data on hormonal AMPK regulation.