Post-graduation Program in Chemical Biology-Institute of Environmental Chemical and Pharmaceutical Sciences, Federal University of São Paulo, Diadema, Brazil.
Universidade Cidade de São Paulo, São Paulo, Brazil.
Obesity (Silver Spring). 2022 Oct;30(10):1995-2004. doi: 10.1002/oby.23537. Epub 2022 Sep 5.
The study goal was to analyze the effects of a high-fat diet (HFD) on the histone 3 lysine 27 (H3K27) posttranscriptional modifications and the expression of histone-modifying enzymes in adipose-derived stromal cells (ASCs) from white adipose tissue (WAT).
Male C57BL/6J mice received control or HFD for 12 weeks. The ASCs were isolated from subcutaneous and visceral (epididymal) WAT, cultivated, and evaluated for expression of H3K27 trimethylation (H3K27me3) and H3K27 acetylation (H3K27ac) by Western blot. The transcription of histone-modifying enzymes was analyzed by real-time polymerase chain reaction.
When compared with control, HFD ASCs showed a decrease in H3K27ac enrichment in subcutaneous and visceral WAT and ATP-citrate lyase expression in subcutaneous WAT. Curiously, the expression of CREB-binding protein was increased in visceral ASCs from HFD-fed mice.
These results show that an HFD significantly reduces acetylation of H3K27 in ASCs and the expression of ATP-citrate lyase in subcutaneous ASCs, suggesting that, in this fat depot, the H3K27ac reduction could be partly due to lower acetyl-coenzyme A availability. H3K27ac is an epigenetic mark responsible for increasing the transcription rate and its reduction can have an important impact on ASC proliferation and differentiation potential.
本研究旨在分析高脂肪饮食（HFD）对白色脂肪组织（WAT）来源的脂肪基质细胞（ASC）中组蛋白 3 赖氨酸 27（H3K27）转录后修饰和组蛋白修饰酶表达的影响。
雄性 C57BL/6J 小鼠接受对照或 HFD 喂养 12 周。从皮下和内脏（附睾）WAT 分离 ASC，进行培养，并通过 Western blot 评估 H3K27 三甲基化（H3K27me3）和 H3K27 乙酰化（H3K27ac）的表达。通过实时聚合酶链反应分析组蛋白修饰酶的转录。
与对照组相比，HFD ASC 显示皮下和内脏 WAT 中 H3K27ac 富集减少，以及皮下 WAT 中 ATP-柠檬酸裂解酶表达降低。有趣的是，HFD 喂养小鼠的内脏 ASC 中 CREB 结合蛋白的表达增加。
这些结果表明，HFD 显著降低了 ASC 中 H3K27 的乙酰化和皮下 ASC 中 ATP-柠檬酸裂解酶的表达，提示在这个脂肪库中，H3K27ac 的减少可能部分归因于乙酰辅酶 A 可用性降低。H3K27ac 是一种负责增加转录率的表观遗传标记，其减少对 ASC 增殖和分化潜力有重要影响。
