Melatonin restores hepatic lipid metabolic homeostasis disrupted by blue light at night in high-fat diet-fed mice.

Artificial light at night (ALAN) is an emerging environmental pollutant that threatens public health. Recently, ALAN has been identified as a risk factor for obesity; however, the role of ALAN and its light wavelength in hepatic lipid metabolic homeostasis remains undetermined. We showed that chronic dim (~5 lx) ALAN (dLAN) exposure significantly promoted hepatic lipid accumulation in obese or diabetic mice, with the most severe effect of blue light and little effect of green or red light. These metabolic phenotypes were attributed to blue rather than green or red dLAN interfering with hepatic lipid metabolism, especially lipogenesis and lipolysis. Further studies found that blue dLAN disrupted hepatic lipogenesis and lipolysis processes by inhibiting hepatic REV-ERBs. Mechanistically, feeding behavior mediated the regulation of dLAN on hepatic REV-ERBs. In addition, different effects of light wavelengths at night on liver REV-ERBs depended on the activation of the corticosterone (CORT)/glucocorticoid receptor (GR) axis. Blue dLAN could activate the CORT/GR axis significantly while other wavelengths could not. Notably, we demonstrated that exogenous melatonin could effectively inhibit hepatic lipid accumulation and restore the hepatic GR/REV-ERBs axis disrupted by blue dLAN. These findings demonstrate that dLAN promotes hepatic lipid accumulation in mice via a short-wavelength-dependent manner, and exogenous melatonin is a potential therapeutic approach. This study strengthens the relationship between ALAN and hepatic lipid metabolism and provides insights into directing ambient light.