AMP-activated protein kinase and its regulation by adiponectin and interleukin-6

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AMP-activated protein kinase (AMPK) is a fuel-sensing enzyme that responds to decreases in cellular energy state by activating processes that generate adenosine triphosphate (ATP) (e.g. fatty acid oxidation), and inhibiting others that consume ATP but are not acutely necessary for survival (e.g. fatty acid, triglyceride and protein synthesis). In contrast, sustained decreases in AMPK or a failure to activate it appropriately have been implicated in the pathogenesis of the metabolic syndrome. Recent studies suggest that various hormones can activate or inhibit AMPK. One of these hormones, adiponectin (Adn), an adipokine released by the fat cell, activates AMPK in liver, muscle, primary rat adipocytes, cultured endothelium and almost certainly other cells. Low plasma levels of Adn are associated with the metabolic syndrome; thus, in both humans and experimental animals, they are often accompanied by obesity, insulin resistance, ectopic lipid deposition, and a predisposition to both type 2 diabetes and atherosclerotic heart disease. Recent studies suggest that thiazoledinediones (TZDs), agents used to treat diabetes because they diminish insulin resistance, exert this effect in great measure by increasing the synthesis and release of adiponectin by the adipocyte and secondarily increasing AMPK activity in the liver and other tissues. Another cytokine that has been shown to activate AMPK is interleukin-6 (IL-6). Studies in IL-6 knockout (KO) mice have revealed that AMPK activity is diminished in their muscle and adipose tissue at 3 months of age and that, like the adiponectin KO mice, they are predisposed to obesity, glucose intolerance and hypertriglyceridemia. Likewise, when bred on an Apo E-/- they develop more severe atherosclerosis than control mice. Whether AMPK activation by other means prevents the development of the metabolic syndrome in the IL-6 or adiponectin KO mice remains to be determined. (copyright) 2006 Taylor & Francis.




Kelly, M., Ruderman, N. B., & Tomas, E. (2006). AMP-activated protein kinase and its regulation by adiponectin and interleukin-6. In Scandinavian Journal of Food and Nutrition (Vol. 50, pp. 85–91).

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