A conserved hormonal signalling-H2A.Z axis rapidly reorganizes 3D chromatin interactions in adipocyte thermogenesis
Zhang Y., Zheng R., Tsuji T., Wang CH., Liu XY., Xing YH.
Animal Study, published in Nat Metab (2026) — 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
- Nat Metab (2026)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 42014869
- PMCID
- PMC13218939
- DOI
- 10.1038/s42255-026-01510-2
Abstract (original English)
Three-dimensional genome organization underlies gene regulation, yet how acute hormonal signalling reshapes chromatin structure to control metabolism remains unclear. β3-adrenergic receptor (β3-AR) hormonal signalling drives adipocyte thermogenesis. Here, we show three-dimensional genome maps of mouse and primary human brown adipocytes during thermogenesis using Micro-C. We find that β3-AR signalling rapidly reorganizes chromatin loops within 4 h, with dynamically gained loops coupled to thermogenic gene activation in both species. Mechanistically, β3-AR stimulation promotes histone variant H2A.Z deposition to enhance chromatin accessibility at loop anchors, facilitating the recruitment of bridging factor MED1. Loss of H2A.Z compromises loop formation and thermogenic gene activation across species. Brown fat-specific H2A.Z deficiency in mice impairs thermogenic activity and glucose tolerance. Integration with genome-wide association studies links H2A.Z-occupied loops to genetic variants associated with obesity and related metabolic disorders. Together, our findings uncover a cross-species conserved β3-AR signalling-H2A.Z axis that rapidly reorganizes chromatin interactions in adipocyte thermogenesis, providing mechanistic and translational insights into metabolic regulation.
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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