Melatonin appears to protect against steroidogenic collapse in both mice fed with high‐fat diet and H2O2‐treated TM3 cells

High‐fat diets (HFDs) are detrimental to steroidogenesis and male fertility. This study aimed to investigate the protective effects of melatonin (MT) treatment on testicular dysfunction in mice fed with HFD. C57BL/6J male mice were randomly divided into three groups: CTRL, HFD and HFD + MT. MT treatment mitigated the increase in body weight and adipose tissue in HFD‐fed mice. Serum levels of sex hormones were improved upon MT supplementation, and the expression of the testosterone synthesis proteins, StAR and P450scc was rescued as well. MT treatment significantly up‐regulated the expression of SIRT1, SOD2, and GPx4 and down‐regulated the expression of GRP78 and CHOP, indicating an attenuation of oxidative stress (OS) and endoplasmic reticulum (ER) stress. In TM3 cells, MT treatment protected against H2O2‐induced steroidogenic collapse by improving mitochondrial function and attenuating OS and ER stress. These results indicate that MT treatment can improve steroidogenesis in mice fed with HFD and may have therapeutic value in the treatment of obesity‐associated hypogonadism.