Obesity (Silver Spring) 2022 Oct 01;3010:1995-2004. doi: 10.1002/oby.23537.

High-fat diet decreases H3K27ac in mice adipose-derived stromal cells.

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OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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