Time-restricted feeding ameliorates hepatic lipid and glucose metabolism dysregulation induced by PM2.5 exposure in mice

Time-restricted feeding (TRF), a diet-related regimen confining food intake to defined daily windows (usually 6–12 h), potentially preventing and managing various metabolic disorders effectively. Growing evidence demonstrates that exposure to fine particulate matter (PM 2.5 ) induces a phenotype resembling metabolic dysfunction-associated fatty liver disease (MAFLD) and disrupts hepatic glucose homeostasis. However, it remains unknown whether TRF could attenuate dysregulated hepatic glucose - lipid metabolism caused by exposure to PM 2.5 and its underlying molecular mechanisms. This study categorized male C57BL/6 N mice into four groups: the filtered air (FA) exposure group, the PM 2.5 exposure group, the TRF + FA exposure group, and the TRF + PM 2.5 exposure group. The PM 2.5 and TRF + PM 2.5 groups were exposed to PM 2.5 in whole-body PM 2.5 exposure chambers, while the remaining groups continued under filtered air. For the TRF + FA and TRF + PM 2.5 groups, feeding was restricted to an 8 - hour period during the active phase (ZT16-ZT24). Our findings revealed that PM 2.5 exposure induced dyslipidemia, glucose intolerance, and insulin resistance (IR), accompanied by elevated hepatic triglyceride (TG) and total cholesterol (TC) levels. Specifically, PM 2.5 disrupted the expression of molecules related to TG, TC and glucose metabolism, and TRF intervention could ameliorate these effects. Furthermore, PM 2.5 exposure suppressed insulin receptor substrate (IRS) and AMP-activated protein kinase (AMPK) signaling pathways, which were reactivated by TRF. In summary, we provide the first evidence that TRF counteracts PM 2.5 -induced insulin resistance and hepatic steatosis, offering a lifestyle strategy against air-pollution-induced pathologies.