National Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Haidian, Beijing, China.
Department of Nutrition and Health, China Agricultural University, Haidian, Beijing, China.
J Pineal Res. 2024 May;76(4):e12963. doi: 10.1111/jpi.12963.
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.
人造光污染（Artificial light at night，ALAN）是一种新兴的环境污染物，威胁着公众健康。最近，ALAN 已被确定为肥胖的危险因素；然而，ALAN 及其光波长在肝脏脂质代谢稳态中的作用仍未确定。我们发现，慢性低强度（~5 lx）人造光（dim artificial light，dLAN）暴露显著促进肥胖或糖尿病小鼠肝脏脂质积累，其中蓝光的作用最严重，绿光和红光的作用较小。这些代谢表型归因于蓝光而非绿光或红光干扰肝脏脂质代谢，特别是脂肪生成和脂肪分解。进一步的研究发现，蓝光 dLAN 通过抑制肝脏 REV-ERBs 来破坏肝脏脂肪生成和脂肪分解过程。在机制上，摄食行为介导了 dLAN 对肝脏 REV-ERBs 的调节。此外，不同波长的夜间光对肝脏 REV-ERBs 的影响取决于皮质酮（corticosterone，CORT）/糖皮质激素受体（glucocorticoid receptor，GR）轴的激活。蓝光 dLAN 可以显著激活 CORT/GR 轴，而其他波长则不能。值得注意的是，我们证明外源性褪黑素可以有效抑制肝脏脂质积累，并恢复蓝光 dLAN 破坏的肝脏 GR/REV-ERBs 轴。这些发现表明，dLAN 通过依赖于短波长的方式促进小鼠肝脏脂质积累，外源性褪黑素是一种潜在的治疗方法。本研究加强了 ALAN 与肝脏脂质代谢之间的关系，并为指导环境光线提供了新的见解。
