Pathophysiological Role And Mechanisms Of Androgen On NAFLD In PCOS Patients

Objective: To explore the effects of androgen on liver fat content(LFC)in patients with polycystic ovary syndrome(PCOS)and its influencing factors,in order to analyze the pathogenic mechanism of androgens in nonalcoholic fatty liver disease(NAFLD)in PCOS patients.Methods: This study elucidated the role of androgen in NAFLD through analyzing the baseline data and cellular experiments,and further proved this effect in PCOS patients before and after treatment.The LFC was measured by quantitative ultrasound,liver fat score and MRI.OPN level was measured by ELISA.Immune cell subsets were measured by flow cytometry analysis.Hep G2 cells and differentiated THP-1 cells were treated with androgen,androgen receptor antagonist and GPR55 inhibitor.Then GPR55,lipid metabolism and inflammation parameters were detected.PCOS patients with impaired glucose tolerance were randomized into 3 groups for the treatments for 12weeks: intensive lifestyle intervention group(n = 10),acarbose group(n = 10),and metformin group(n = 10).Results: Androgen in PCOS patients might have a dimorphic role in LFC.LFC in PCOS patients might predict impaired glucose regulation,lipid metabolic disorder and insulin resistance.In PCOS patients,OPN and CD4+T/T cell ratio could be used as independent risk factors for LFC.The expression of GPR55 was increased by androgen/androgen receptor.The elevated GPR55 induced lipogenesis genes expression in Hep G2 cells and pro-inflammatory genes expression in THP-1 cells through ERK signaling pathway.The changes in androgen levels were positively correlated with changes in LFC before and after treatment in PCOS patients Conclusion: Androgen played an important role in the development of NAFLD in PCOS patients.Androgen might influence the progression of NAFLD through OPN,immune cells,and GPR55.This study elaborated the potential early prediction of warning targets in PCOS patients with NAFLD,and has important clinical significance.