MAPK signalling in cellular metabolism: stress or wellness?

The crucial roles of MAPKs in health and in disease are discussed. MAPK-dependent signalling is required for physiological metabolic adaption, but its inappropriate activation contributes to the development of metabolic syndrome and its life-threatening clinical consequences, such as type 2 diabetes

Dietary obesity-associated Hif1α activation in adipocytes restricts fatty acid oxidation and energy expenditure via suppression of the Sirt2-NAD+ system

Dietary obesity is a major determinant of type 2 diabetes and is characterized by enlarged white adipose tissue. Such tissue is poorly oxygenated, leading to hypoxia and activation of HIF1α. Krek and colleagues uncover a central role for HIF1α in promoting and maintaining such obesity. HIF1α directly represses a Sirt2–Pgc1α pathway that controls adipocyte fatty acid oxidation and energy expenditure. The work thus outlines a regulatory pathway that is initiated within obesity-associated hypoxic tissue mass and that then creates a metabolic state supportive of pathological tissue expansion