Endocrine Abstracts

The metabolic enzyme adenosine monophosphate-activated protein kinase (AMPK) was originally discovered as a regulator of cellular energy homeostasis. It protects and replenishes cellular ATP via stimulating catabolic processes such as glycolysis and lipid oxidation, and inhibiting anabolic processes such as lipid synthesis and gluconeogenesis in peripheral tissues (liver, adipose or muscle cells). However, more recently it has emerged that AMPK activation in the hypothalamus leads to increased food intake thereby securing appropriate energy supply at the level of the whole organism. Hypoglycaemia is a strong stimulus to hypothalamic AMPK activation, whereas co-administration of compound C, an AMPK inhibitor, inhibited 2-deoxyglucose-induced glucoprivic feeding. Appetite stimulating agents (ghrelin, cannabinoids or AgRP) stimulate, while anorectic compounds (leptin, insulin or α-MSH) inhibit hypothalamic AMPK, but individual nuclei and cell types may respond differentially. The regulation of AMPK by hormones has an intriguing tissue-specific aspect. While leptin is an AMPK-inhibitor in the hypothalamus and ghrelin is a stimulator, in liver tissue leptin stimulates while ghrelin inhibits AMPK activity. The antidiabetic agent metformin and the glitazones also stimulate AMPK in the periphery while metformin inhibits it in the hypothalamus. Other processes, however, such as hypoglycaemia show activation in all the tissue studied. In general, the differential effects at varying tissue sites act in a concerted manner to consolidate the energy supply of the organism at cellular and tissue levels. Recent studies have illustrated the interaction between hormones and AMPK, and have highlighted AMPK as a potential target for the development of tissue-specific AMPK modulators in the treatment of obesity and the metabolic syndrome.