PRDM16 stability and metabolically healthy adipose tissue

PRDM16 is a key thermogenic fat mediator, counteracting adipose fibrosis and inflammation. Kajimura and co-authors demonstrate that an ubiquitin E3 ligase CUL2–APPBP2 complex destabilizes the PRDM16 protein, leading to an age-dependent decrease in metabolic activity.

Adipose tissue has energy storage and immunogenic properties, and encompasses all parts of the mammalian body. However, the specific properties of healthy adipose tissue vary by location. Brown adipose tissue (BAT) is a thermogenic organ, which switches between states of energy storage and energy consumption. White adipose tissue (WAT) is a safe energy storage compartment that switches between storing and releasing energy. These deposits are differentially composed by subtypes of adipocytes specialized for, for example, lipogenesis, thermogenesis or insulin signaling1. Functional studies in mice have identified the PR domain containing protein 16 (PRDM16) as a key mediator of metabolically healthy adipose tissue in all depots2,3,4. Now recent work in Nature by Wang et al5. advances our knowledge of PRDM16 regulation and function by providing insights into the post-translational control of PRDM16 levels.

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