Loss of histone methyltransferase Smyd3 triggers WAT browning and adaptive thermogenesis via enhancing PPARγ expression in a H4K20me3-dependent manner.

ABSTRACT: Adaptive thermogenesis driven by brown/beige adipose tissue has gained attention as a promising strategy for combating obesity. Histone methyltransferase SET and MYND Domain Containing 3 (Smyd3) is strongly associated with metabolic and cardiovascular diseases, however, its role in adaptive thermogenesis has not been well characterized. Here, we demonstrate that Smyd3 is abundant and closely involved in adipocyte thermogenic programming. However, genetic ablation of Smyd3 or pharmacological inhibition with the specific inhibitor EPZ031686 robustly enhanced adaptive thermogenesis in mice. Conversely, Smyd3 overexpression attenuated white adipose tissue (WAT) browning both in vivo and in vitro. Mechanistically, we found that loss of Smyd3 (pharmacological inhibition by EPZ031686, knockdown b

SUBMITTER: Shu M 

PROVIDER: S-EPMC12486502 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature