Naringenin alleviates the excessive lipid deposition of polycystic ovary syndrome rats and insulin‐resistant adipocytes by promoting PKGIα

Abstract

AbstractBackgroundNaringenin (NGEN) has anti‐inflammatory and anti‐diabetic effects. On this basis, this study aims to determine whether NGEN affects insulin resistance (IR) in polycystic ovary syndrome (PCOS).MethodsCCK‐8 assay and oil red O staining were used to detect the cytotoxicity of NGEN and lipid production in cells or tissues, respectively. The differentiated mature SW872 cells were treated with palmitic acid (PA) to mimic IR cell model. Through detecting glucose consumption, the changes of inflammation and glycolipid metabolism can be observed with the assessment on expression levels of the inflammatory factors as well as lipid synthesis‐ (ACC, SREBP1c, PPARγ), glucose metabolism‐ and thermogenesis (ATGL, GLUT4, UCP1)‐related genes. Insulin sensitivity was determined by changes in glucose consumption and PKGIα pathway. PKGIα was silenced to verify the protective mechanism of NGEN. PCOS rat model was constructed to confirm the results of cell experiments in vivo.ResultsNGEN generated no effect on SW872 cell viability. SW872 cells were differentiated and mature, as evidenced by lipid droplet formation, lipid synthesis gene activation, sugar metabolism and inhibition of thermogenesis‐related genes. PA induction promoted lipid synthesis in mature adipocytes, and inhibited glucose metabolism and cell insulin sensitivity. NGEN pretreatment effectively alleviated the above‐mentioned abnormalities. The protective mechanism of NGEN was achieved through promoting PKGIα activation. NGEN also mitigated the abnormal glucose and lipid metabolism in PCOS rats.ConclusionNGEN inhibits the expression of PKGIα to alleviate IR that occurs in PCOS.