TET3 在白色脂肪组织发育和饮食诱导的重塑中起着关键作用。
TET3 plays a critical role in white adipose development and diet-induced remodeling.
机构信息
Nutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA.
Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA; The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.
出版信息
Cell Rep. 2023 Oct 31;42(10):113196. doi: 10.1016/j.celrep.2023.113196. Epub 2023 Sep 30.
Maintaining healthy adipose tissue is crucial for metabolic health, requiring a deeper understanding of adipocyte development and response to high-calorie diets. This study highlights the importance of TET3 during white adipose tissue (WAT) development and expansion. Selective depletion of Tet3 in adipose precursor cells (APCs) reduces adipogenesis, protects against diet-induced adipose expansion, and enhances whole-body metabolism. Transcriptomic analysis of wild-type and Tet3 knockout (KO) APCs unveiled TET3 target genes, including Pparg and several genes linked to the extracellular matrix, pivotal for adipogenesis and remodeling. DNA methylation profiling and functional studies underscore the importance of DNA demethylation in gene regulation. Remarkably, targeted DNA demethylation at the Pparg promoter restored its transcription. In conclusion, TET3 significantly governs adipogenesis and diet-induced adipose expansion by regulating key target genes in APCs.
维持健康的脂肪组织对于代谢健康至关重要，这需要我们更深入地了解脂肪细胞的发育和对高热量饮食的反应。本研究强调了 TET3 在白色脂肪组织（WAT）发育和扩张中的重要性。选择性敲除脂肪前体细胞（APCs）中的 Tet3 会减少脂肪生成，防止饮食诱导的脂肪扩张，并增强全身代谢。对野生型和 Tet3 敲除（KO）APC 的转录组分析揭示了 TET3 的靶基因，包括 Pparg 和几个与细胞外基质相关的基因，这些基因对脂肪生成和重塑至关重要。DNA 甲基化分析和功能研究强调了 DNA 去甲基化在基因调控中的重要性。值得注意的是，在 Pparg 启动子上靶向性的 DNA 去甲基化恢复了其转录。总之，TET3 通过调节 APCs 中的关键靶基因显著调控脂肪生成和饮食诱导的脂肪扩张。
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