Association of sex hormones and sex hormone-binding globulin with liver fat in men and women: an observational and Mendelian randomization study

Frontiers in Endocrinology

Endocrinology

Hanieh Yaghootkar¹  Alexander Cecil²  Cornelia Prehn²  Simon Hohenester³  Jana Nano⁴  Barbara Thorand⁵  Annette Peters⁶  Xinting Cai⁷  Jerzy Adamski⁸  Andrea Dennis⁹  Rajarshi Banerjee⁹  Tanja Zeller^1,10 

[1] College of Health and Science, University of Lincoln, Joseph Banks Laboratories, Green Lane, Lincoln, Lincolnshire, United Kingdom;Core Facility Metabolomics and Proteomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;Department of Medicine II, University Hospital, Ludwig-Maximilians University of Munich, Munich, Germany;Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;Institute for Medical Information Processing, Biometry, and Epidemiology – IBE, Faculty of Medicine, Ludwig-Maximilians University of Munich, Munich, Germany;Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;Institute for Medical Information Processing, Biometry, and Epidemiology – IBE, Faculty of Medicine, Ludwig-Maximilians University of Munich, Munich, Germany;German Center for Diabetes Research (DZD), partner site Munich-Neuherberg, Neuherberg, Germany;Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;Institute for Medical Information Processing, Biometry, and Epidemiology – IBE, Faculty of Medicine, Ludwig-Maximilians University of Munich, Munich, Germany;German Center for Diabetes Research (DZD), partner site Munich-Neuherberg, Neuherberg, Germany;German Center for Cardiovascular Disease Research (DZHK), partner site Munich Heart Alliance, Munich, Germany;Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;Institute for Medical Information Processing, Biometry, and Epidemiology – IBE, Faculty of Medicine, Ludwig-Maximilians University of Munich, Munich, Germany;Pettenkofer School of Public Health, Ludwig-Maximilians University of Munich, Munich, Germany;Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Queenstown, Singapore;Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia;Perspectum, Oxford, United Kingdom;University Center of Cardiovascular Science, University Heart and Vascular Center Hamburg, Hamburg, Germany;Clinic of Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany;German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany;

关键词: sex hormones;    sex hormone-binding globulin;    fatty liver index;    liver fat;    Mendelian randomization;    European cohort;   

DOI  :  10.3389/fendo.2023.1223162

 received in 2023-05-15, accepted in 2023-09-11,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundSex hormones and sex hormone-binding globulin (SHBG) may play a role in fatty liver development. We sought to examine the association of various endogenous sex hormones, including testosterone (T), and SHBG with liver fat using complementary observational and Mendelian randomization (MR) analyses.MethodsThe observational analysis included a total of 2,239 participants (mean age 60 years; 35% postmenopausal women) from the population-based KORA study (average follow-up time: 6.5 years). We conducted linear regression analysis to investigate the sex-specific associations of sex hormones and SHBG with liver fat, estimated by fatty liver index (FLI). For MR analyses, we selected genetic variants associated with sex hormones and SHBG and extracted their associations with magnetic resonance imaging measured liver fat from the largest up to date European genome-wide associations studies.ResultsIn the observational analysis, T, dihydrotestosterone (DHT), progesterone and 17α-hydroxyprogesterone (17-OHP) were inversely associated with FLI in men, with beta estimates ranging from -4.23 to -2.30 [p-value <0.001 to 0.003]. Whereas in women, a positive association of free T with FLI (β = 4.17, 95%CI: 1.35, 6.98) was observed. SHBG was inversely associated with FLI across sexes [men: -3.45 (-5.13, -1.78); women: -9.23 (-12.19, -6.28)]. No causal association was found between genetically determined sex hormones and liver fat, but higher genetically determined SHBG was associated with lower liver fat in women (β = -0.36, 95% CI: -0.61, -0.12).ConclusionOur results provide suggestive evidence for a causal association between SHBG and liver fat in women, implicating the protective role of SHBG against liver fat accumulation.

【 授权许可】

Unknown   
Copyright © 2023 Cai, Thorand, Hohenester, Prehn, Cecil, Adamski, Zeller, Dennis, Banerjee, Peters, Yaghootkar and Nano