Per2 contributes to chronic noise-induced hepatic lipogenesis associated with PPARγ/SREBP-1 signaling

Chronic noise exposure is increasingly recognized as an environmental risk factor for metabolic disorders; however, whether and how circadian dysregulation contributes to noise-induced hepatic lipid abnormalities remains unclear. Here, we investigated the role of circadian regulation in chronic noise-induced hepatic lipid metabolic alterations using transcriptomic, metabolomic, and genetic approaches. Thirty-day noise exposure in C57BL/6 J mice induced hepatic lipid accumulation and mild histopathological changes without affecting body weight or food intake. Noise exposure altered the temporal regulation of hepatic lipid metabolism, characterized by increased hepatic triglyceride accumulation and altered expression of fatty acid metabolic genes, including Fads2 and Elovl6. Transcriptomic profiling identified 613 genes with altered rhythmic expression patterns enriched in lipid metabolic and circadian-related pathways, with the core clock gene Per2 emerging as a candidate hub gene. qPCR-based circadian analysis and time-resolved protein validation demonstrated altered PER2 expression accompanied by changes in PPARγ/SREBP-1 signaling components. Untargeted metabolomics further revealed noise-associated lipogenic metabolic alterations, which were partially attenuated by Per2 deletion. Mechanistically, Per2 knockout alleviated noise-associated hepatic lipid abnormalities and reduced the induction of Srebf1 expression and PPARγ/SREBP-1 protein abundance. Collectively, these findings identify Per2 as an important circadian regulator involved in noise-induced hepatic lipogenic responses and provide new insights into the link between environmental stress, circadian regulation, and metabolic dysfunction.