Involvement of obesity-associated upregulation of chemerin/chemokine-like receptor 1 in oxidative stress and apoptosis in ovaries and granulosa cells.

In this study, we evaluated the expression and function of chemerin and CMKLR1 in the ovaries and granulosa cells of high-fat diet-induced obese (OB) mice. In vivo, chemerin/CMKLR1 system was upregulated in the serum, ovaries, and granulosa cells of OB mice compared with those in control mice. Apoptotic ovarian follicles, oxidative stress, and apoptosis biomarkers were also increased in the ovaries of OB mice. In vitro, mouse granulosa cells (mGCs) were cultured and treated with different concentrations of chemerin to investigate the effects of chemerin on viability, reactive oxygen species (ROS), and apoptosis and on the phosphorylation of AKT, AMP-activated protein kinase α (AMPKα), and nuclear factor-κB p65. Chemerin suppressed mGC viability with or without gonadotrophin and induced ROS accumulation and apoptosis in mGCs. Moreover, AMPKα and p65 were activated by chemerin, whereas AKT was suppressed. These changes in phosphorylation were blocked with CMKLR1 knockdown. Our findings showed that chemerin contributed to ROS accumulation and apoptotic cell death through three signaling pathways, suggesting that upregulation of chemerin and CMKLR1 may explain the imbalance of oxidative stress and apoptosis in the ovaries of OB mice.