Hyperglycemia Inhibits Hepatic SHBG Synthesis Through the NGBR‐AMPK‐HNF4 Pathway in Rats with Polycystic Ovary Syndrome Induced by Letrozole in Combination with a High‐Fat Diet

Abstract

ScopePolycystic ovary syndrome (PCOS) is closely related to non‐alcoholic fatty liver disease (NAFLD), and sex hormone‐binding globulin (SHBG) is a glycoprotein produced by the liver. Hepatic lipogenesis inhibits hepatic SHBG synthesis, which leads to hyperandrogenemia and ovarian dysfunction in PCOS. Therefore, this study aims to characterize the mechanism whereby liver lipogenesis inhibits SHBG synthesis.Methods and resultsThis study establishes a rat model of PCOS complicated by NAFLD using a high‐fat diet in combination with letrozole and performs transcriptomic analysis of the liver. Transcriptomic analysis of the liver shows that the expression of neurite growth inhibitor‐B receptor (NgBR), hepatocyte nuclear factor 4α (HNF4α), and SHBG is low. Meantime, HepG2 cells are treated with palmitic acid (PA) to model NAFLD in vitro, which causes decreases in the expression of NgBR, HNF4α, and SHBG. However, the expression of HNF4α and SHBG is restored by treatment with the AMP‐activated protein kinase (AMPK) agonist AICAR.ConclusionsNgBR regulates the expression of HNF4α by activating the AMPK signaling pathway, thereby affecting the synthesis of SHBG in the liver. Further mechanistic studies regarding the effect of liver fat on NGBR expression are warranted.