Melatonin attenuates hepatic oxidative stress by regulating the P62/LC3 autophagy pathway in PCOS

作者：Junhui Zhang, Hongyan Zhang, Bao Guo, H. J. Yang, Renxiang Yu, Wenxiu Chen, Muxin Zhai, Cao Yuhan, Yajing Liu, Qiang Hong, Fenfen Xie · 发表于：Endocrine Connections · 年份：2024 · DOI：10.1530/ec-24-0303 · 被引用次数：4 · 研究领域：Diet, Metabolism, and Disease、Liver Disease Diagnosis and Treatment、Ovarian function and disorders

Graphical abstract The potential protective mechanisms of MT on hepatic OS in PCOS. MT could lead to a decrease in autophagy, presenting a decrease of LC3 and an increase of P62 in the PCOS liver. Increased P62 could reduce Nrf2 ubiquitination and increase its nuclear translocation and activation through direct interaction with Keap1. Thus, MT ultimately activated the Keap1-Nrf2 pathway, promoting nuclear Nrf2 expression to reduce hepatic OS. Abstract The elevated level of hepatic oxidative stress (OS) in polycystic ovary syndrome (PCOS) is one of the important causes of liver abnormalities. Therefore, decreasing the level of hepatic OS in PCOS is beneficial in reducing the risk of PCOS-related liver diseases. Melatonin (MT) is recognized as a potent antioxidant. Nevertheless, the efficacy of MT in alleviating hepatic OS associated with PCOS is yet to be established, and the precise mechanisms through which MT exerts its antioxidant effects remain to be fully elucidated. The aim of this study was to explore the potential mechanisms by which MT reduces hepatic OS in PCOS. First, we detected elevated OS levels in PCOS samples. Subsequently, with MT pretreatment, we discovered that MT could significantly diminish the levels of OS, liver triglycerides, total cholesterol, alanine aminotransferase, and aspartate aminotransferase, while concurrently ameliorating mitochondrial structural damage in the PCOS liver. Furthermore, we identified elevated autophagy levels in the liver of PC...