Loss of histone methyltransferase Smyd3 triggers WAT browning and adaptive thermogenesis via enhancing PPARγ expression in a H4K20me3-dependent manner
Shu M., Ma Y., Zhao D., Meng C., Chen L., Wang L.
Animal Study, published in J Transl Med (2025) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Animal Study
- Journal
- J Transl Med (2025)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 41034941
- PMCID
- PMC12486502
- DOI
- 10.1186/s12967-025-07072-3
- Citations
- 2
Abstract (original English)
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 by Smyd3 siRNA and genetic ablation by Smyd3-KO mice) decreased the trimethylation of histone H4 lysine 20 (H4K20) within the promoter region of the transcription factor Peroxisome proliferator-activated receptor gamma (Pparg) gene and released the transcription suppression, thereby upregulating PPARγ expression, which initiates the transcription of thermogenic genes such as Uncoupling protein 1 (Ucp1), ultimately promoting the protein expression of UCP1 in the cytoplasm and triggering the adaptive thermogenesis program. Collectively, our findings identify Smyd3 as a potential therapeutic targe
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
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