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

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...

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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Journal of Clinical Medicine
Subjects:
Online Access:https://www.mdpi.com/2077-0383/12/2/451
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author 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
author_facet 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
author_sort Nan Lu
collection DOAJ
description 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 (<i>p</i> 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/m<sup>2</sup> (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.
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spelling doaj.art-278d52d37b864f72904857a55bd6cf402023-11-30T22:50:08ZengMDPI AGJournal of Clinical Medicine2077-03832023-01-0112245110.3390/jcm12020451RANKL Is Independently Associated with Increased Risks of Non-Alcoholic Fatty Liver Disease in Chinese Women with PCOS: A Cross-Sectional StudyNan Lu0Chang Shan1Jia-Rong Fu2Yi Zhang3Yu-Ying Wang4Yu-Chen Zhu5Jie Yu6Jie Cai7Sheng-Xian Li8Tao Tao9Wei Liu10Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, ChinaDepartment of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, ChinaDepartment of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, ChinaDepartment of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, ChinaDepartment of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, ChinaDepartment of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, ChinaDepartment of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, ChinaDepartment of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, ChinaDepartment of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, ChinaDepartment of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, ChinaDepartment of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, ChinaWomen 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 (<i>p</i> 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/m<sup>2</sup> (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.https://www.mdpi.com/2077-0383/12/2/451receptor activator of NF-κB ligandnon-alcoholic fatty liver diseasepolycystic ovary syndromefree androgen indexinsulin resistance
spellingShingle 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
RANKL Is Independently Associated with Increased Risks of Non-Alcoholic Fatty Liver Disease in Chinese Women with PCOS: A Cross-Sectional Study
Journal of Clinical Medicine
receptor activator of NF-κB ligand
non-alcoholic fatty liver disease
polycystic ovary syndrome
free androgen index
insulin resistance
title RANKL Is Independently Associated with Increased Risks of Non-Alcoholic Fatty Liver Disease in Chinese Women with PCOS: A Cross-Sectional Study
title_full RANKL Is Independently Associated with Increased Risks of Non-Alcoholic Fatty Liver Disease in Chinese Women with PCOS: A Cross-Sectional Study
title_fullStr RANKL Is Independently Associated with Increased Risks of Non-Alcoholic Fatty Liver Disease in Chinese Women with PCOS: A Cross-Sectional Study
title_full_unstemmed RANKL Is Independently Associated with Increased Risks of Non-Alcoholic Fatty Liver Disease in Chinese Women with PCOS: A Cross-Sectional Study
title_short RANKL Is Independently Associated with Increased Risks of Non-Alcoholic Fatty Liver Disease in Chinese Women with PCOS: A Cross-Sectional Study
title_sort rankl is independently associated with increased risks of non alcoholic fatty liver disease in chinese women with pcos a cross sectional study
topic receptor activator of NF-κB ligand
non-alcoholic fatty liver disease
polycystic ovary syndrome
free androgen index
insulin resistance
url https://www.mdpi.com/2077-0383/12/2/451
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