Intensive lifestyle intervention modulates white adipose glycolipid metabolism via protein acetylation associated with Ep300

The homeostatic regulation of white adipose tissue (WAT) is crucial for maintain energy and metabolism balance. Plenty of clinical trials proved that intensive lifestyle intervention (ILI) improved fat accumulation in patients with obesity. Yet the underlying acetylated regulations of WAT during ILI remain incompletely understood. Here, we build a model to simulate this condition and use multi-omics data from WAT to depict the complicated regulation patterns. The results showed non-histones acetylation were mainly involved in glycolipid metabolism centered on acetyl-CoA. A novel site on histones, H3K36ac, showed a relationship with ILI. Based on the association between Ep300 and process of ILI after DIO, a localized lentivirus designed to suppress Ep300 to loss body weight showed an obvious weight reduction and alleviate dyslipidemia effect. Overall, this study reveals the intricacies of acetylation response to ILI and provide novel sights on finding Ep300 lentivirus as a potential therapeutic strategy of obesity.