Cell Metabolism
Volume 19, Issue 4, 1 April 2014, Pages 593-604
Journal home page for Cell Metabolism

Article
Prdm16 Is Required for the Maintenance of Brown Adipocyte Identity and Function in Adult Mice

https://doi.org/10.1016/j.cmet.2014.03.007Get rights and content
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Highlights

  • Prdm16 is dispensable for embryonic brown adipose tissue (BAT) development

  • Prdm16 recruits Ehmt1 to repress white-fat-selective gene expression in BAT

  • Prdm16 is required to maintain brown fat identity/function during aging

  • Prdm3 compensates for the loss of Prdm16 to preserve BAT identity in young mice

Summary

Prdm16 is a transcription factor that regulates the thermogenic gene program in brown and beige adipocytes. However, whether Prdm16 is required for the development or physiological function of brown adipose tissue (BAT) in vivo has been unclear. By analyzing mice that selectively lacked Prdm16 in the brown adipose lineage, we found that Prdm16 was dispensable for embryonic BAT development. However, Prdm16 was required in young mice to suppress the expression of white-fat-selective genes in BAT through recruitment of the histone methyltransferase Ehmt1. Additionally, Prdm16 deficiency caused a severe adult-onset decline in the thermogenic character of interscapular BAT. This resulted in BAT dysfunction and cold sensitivity but did not predispose the animals to obesity. Interestingly, the loss of brown fat identity due to ablation of Prdm16 was accelerated by concurrent deletion of the closely related Prdm3 gene. Together, these results show that Prdm16 and Prdm3 control postnatal BAT identity and function.

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