PRDM16 stability and metabolically healthy adipose tissue

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

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ADIPOSE TISSUE

Nature Metabolism

(2022)Cite this article

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

Adipose tissue has energy-storing and immunogenic properties, and embeds all parts of the mammalian body. However, the specific properties of healthy adipose tissue vary with location. Brown adipose tissue (BAT) is a thermogenic organ, which switches between energy-storing and energy-consuming states. White adipose tissue (WAT) is a safe energy-storing compartment that switches between storing and releasing energy. These depots are differentially composed by adipocyte subtypes that are specialized for, for example, lipogenesis, thermogenesis or insulin signalling1. Functional studies in mice have pinpointed PR domain containing protein 16 (PRDM16) as a key mediator of metabolically healthy adipose tissue across 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.