RANKL Is Independently Associated with Increased Risks of Non-Alcoholic Fatty Liver Disease in Chinese Women with PCOS: A Cross-Sectional Study

Nan Lu; Chang Shan; Jia-Rong Fu; Yi Zhang; Yu-Ying Wang; Yu-Chen Zhu; Jie Yu; Jie Cai; Sheng-Xian Li; Tao Tao; Wei Liu

doi:10.3390/jcm12020451

RANKL Is Independently Associated with Increased Risks of Non-Alcoholic Fatty Liver Disease in Chinese Women with PCOS: A Cross-Sectional Study

J Clin Med. 2023 Jan 5;12(2):451. doi: 10.3390/jcm12020451.

Authors

Nan Lu¹, Chang Shan¹, Jia-Rong Fu¹, Yi Zhang¹, Yu-Ying Wang¹, Yu-Chen Zhu¹, Jie Yu¹, Jie Cai¹, Sheng-Xian Li¹, Tao Tao¹, Wei Liu¹

Affiliation

¹ Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.

Abstract

Women with polycystic ovarian syndrome (PCOS) are more likely to have non-alcoholic fatty liver disease (NAFLD) than non-PCOS women; however, the exact mechanism underlying this trend is unknown. The receptor activator of NF-κB ligand (RANKL) is strongly involved in bone metabolism and has multiple functions. Recent studies suggest that RANKL is implicated in hepatic insulin resistance (IR), which is the highest risk factor for NAFLD. This study aimed to assess the role of RANKL in NAFLD in Chinese women with PCOS. A cross-sectional observational study was conducted on women newly diagnosed with PCOS, which included 146 patients with NAFLD and 142 patients without NAFLD. Sex hormones, glucose, insulin, and lipids were measured, and anthropometric data were collected. The concentration of serum total RANKL was measured using commercial ELISA kits. PCOS patients with NAFLD had a significantly higher mean age, body mass index (BMI), waist circumference (WC), and worsened metabolic profile than non-NAFLD subjects. The concentrations of high-sensitivity C-reactive protein, total cholesterol, and low-density lipoprotein cholesterol increased with the RANKL tertile (p for trend = 0.023, 0.026, and 0.035, respectively). A significantly positive association was found between RANKL (per SD change) and the risks of NAFLD (OR = 1.545, 95% CI = 1.086−2.199) after adjusting for confounders, including demographic factors, metabolic markers, and sex hormones. Subgroup multivariate logistic analyses stratified by age, BMI, and WC showed the same tendency. In addition, the positive association between RANKL and NAFLD seemed more prominent in lean patients with a BMI < 24 kg/m2 (OR = 1.70, 95% CI = 1.06−2.75) when compared to overweight/obesity subjects. Therefore, this study suggests that RANKL is positively associated with the increased risk of NAFLD in Chinese women with PCOS, independent of metabolic and reproductive factors.

Keywords: free androgen index; insulin resistance; non-alcoholic fatty liver disease; polycystic ovary syndrome; receptor activator of NF-κB ligand.

Grants and funding

This research was funded by the National Natural Science Foundation of China (81800779, 82170807, 81800693, 31900821); the grant of Major Chronic Non-Communicable Disease Prevention and Control Research, National Key R&D Program of China (2016YFC1305600, 2016YFC1305602).