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The association between thyroid hormones and MAFLD is mediated by obesity and metabolic disorders and varies among MAFLD subtypes

  • Author Footnotes
    1 These authors contributed equally to this work.
    Hong Fan
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China. Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, China

    Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, China

    Fudan University Taizhou Institute of Health Sciences, Taizhou, China
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Lili Li
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China. Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, China

    Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, China
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  • Zhenqiu Liu
    Affiliations
    Fudan University Taizhou Institute of Health Sciences, Taizhou, China

    State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200438, China

    Human Phenome Institute, Fudan University, Shanghai, China
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  • Liou Cao
    Affiliations
    Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, China
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  • Xingdong Chen
    Affiliations
    Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, China

    Fudan University Taizhou Institute of Health Sciences, Taizhou, China

    State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200438, China

    Human Phenome Institute, Fudan University, Shanghai, China
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  • Chen Suo
    Correspondence
    Corresponding authors at: School of Public Health, Fudan University, Shanghai, 200032, China.
    Affiliations
    Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China. Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, China

    Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, China

    Fudan University Taizhou Institute of Health Sciences, Taizhou, China
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  • Tiejun Zhang
    Correspondence
    Corresponding authors at: School of Public Health, Fudan University, Shanghai, 200032, China.
    Affiliations
    Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China. Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, China

    Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, China

    Fudan University Taizhou Institute of Health Sciences, Taizhou, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.
Published:December 17, 2022DOI:https://doi.org/10.1016/j.dld.2022.11.020

      Abstract

      Background

      Thyroid hormone (TH) disorders increased the risk of metabolic dysfunction-associated fatty liver disease (MAFLD).

      Aim

      To assess whether the association between TH and MAFLD is mediated via metabolic dysfunctions and varies among MAFLD subtypes (diabetes-MAFLD, overweight/obesity-MAFLD, metabolic disorders-MAFLD).

      Methods

      A total of 18,427 participants (661 diabetes-MAFLD, 3,600 overweight/obesity-MAFLD, 691 metabolic disorder-MAFLD cases, 13,475 non-MAFLD controls) from a Chinese hospital were enrolled. Hepatic ultrasound measurements and thyroid function were assessed.

      Results

      Overweight/obesity mediated the associations of MAFLD with triiodothyronine (T3), free triiodothyronine (FT3), free thyroxine (FT4), and the mediator accounted for 46.43%, 39.69%, and 42.68%, respectively. Metabolic disorder mediated the association of MAFLD with T3, FT3, FT4, thyroid stimulating hormone (TSH), and the mediator accounted for 36.57%, 23.19%, 34,65%, and 60.92%, respectively. Diabetes did not complementary mediate any association between TH and MAFLD. Elevated T3, FT3, TSH and decreased FT4 increased the risk of overweight/obesity-MAFLD, and the odds ratios were 1.59, 1.72, 1.18, and 0.60, respectively (Q4 vs.Q1, false discovery rate (FDR)<0.05). Elevated T3, FT3, and decreased FT4 increased the risk of metabolic disorder-MAFLD, and the odds ratios were 1.45, 1.33, and 0.52, respectively (Q4 vs.Q1, FDR<0.05). No significant association between TH and diabetes-MAFLD was detected.

      Conclusion

      The association between TH and MAFLD is mediated by overweight/obesity and metabolic disorders and varies among MAFLD subtypes.

      Keywords

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      References

        • Sinha R.A.
        • Singh B.K.
        • Yen P.M
        Direct effects of thyroid hormones on hepatic lipid metabolism.
        Nat Rev Endocrinol. 2018; 14: 259-269
        • Ritter M.J.
        • Amano I.
        • Hollenberg A.N
        Thyroid Hormone Signaling and the Liver.
        Hepatology. 2020; 72: 742-752
        • Fuchs C.D.
        • Claudel T.
        • Trauner M
        Role of metabolic lipases and lipolytic metabolites in the pathogenesis of NAFLD. Trends in endocrinology and metabolism.
        TEM. 2014; 25: 576-585
        • Harrison S.A.
        • Bashir M.R.
        • Guy C.D.
        • et al.
        Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.
        Lancet. 2019; 394: 2012-2024
        • Eslam M.
        • Newsome P.N.
        • Sarin S.K.
        • et al.
        A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement.
        J Hepatol. 2020; 73: 202-209
        • Hernaez R.
        • Peck-Radosavljevic M
        MAFLD, HCC and the dilemma of (changing) terminology in liver diseases.
        Gut. 2022;
        • Chen X.
        • Chen S.
        • Pang J.
        • et al.
        Are the different MAFLD subtypes based on the inclusion criteria correlated with all-cause mortality?.
        J Hepatol. 2021; 75: 987-989
        • Berzigotti A.
        • Boursier J.
        • Castera L.
        • et al.
        Easl Clinical Practice Guidelines (Cpgs) On Non-Invasive Tests For Evaluation Of Liver Disease Severity And Prognosis- 2020 Update.
        J Hepatol. 2021;
        • Angulo P.
        • Hui J.M.
        • Marchesini G.
        • et al.
        The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD.
        Hepatology. 2007; 45: 846-854
        • Kim D.
        • Kim W.R.
        • Kim H.J.
        • et al.
        Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States.
        Hepatology. 2013; 57: 1357-1365
        • van den Berg E.H.
        • van Tienhoven-Wind L.J.
        • Amini M.
        • et al.
        Higher free triiodothyronine is associated with non-alcoholic fatty liver disease in euthyroid subjects: the Lifelines Cohort Study.
        Metabolism. 2017; 67: 62-71
        • Gökmen F.Y.
        • Ahbab S.
        • Ataoğlu H.E.
        • et al.
        FT3/FT4 ratio predicts non-alcoholic fatty liver disease independent of metabolic parameters in patients with euthyroidism and hypothyroidism.
        Clinics. 2016; 71: 221-225
        • Tan Y.
        • Tang X.
        • Mu P.
        • et al.
        High-normal serum thyrotropin levels increased the risk of non-alcoholic fatty liver disease in euthyroid subjects with type 2 diabetes.
        Diabetes Metab Syndr Obes. 2021; 14: 2841-2849
        • Mantovani A.
        • Nascimbeni F.
        • Lonardo A.
        • et al.
        Association between primary hypothyroidism and nonalcoholic fatty liver disease: a systematic review and meta-analysis.
        Thyroid. 2018; 28: 1270-1284
        • Kim D.
        • Kim W.
        • Joo S.K.
        • et al.
        Subclinical hypothyroidism and low-normal thyroid function are associated with nonalcoholic steatohepatitis and fibrosis.
        Clin Gastroenterol Hepatol. 2018; 16 (e1): 123-131
        • Ludwig U.
        • Holzner D.
        • Denzer C.
        • et al.
        Subclinical and clinical hypothyroidism and non-alcoholic fatty liver disease: a cross-sectional study of a random population sample aged 18 to 65 years.
        BMC Endocr Disord. 2015; 15: 41
        • Xu C.
        • Xu L.
        • Yu C.
        • et al.
        Association between thyroid function and nonalcoholic fatty liver disease in euthyroid elderly Chinese.
        Clin Endocrinol (Oxf). 2011; 75: 240-246
        • Guo W.
        • Qin P.
        • Li X.N.
        • et al.
        Free triiodothyronine is associated with hepatic steatosis and liver stiffness in euthyroid chinese adults with non-alcoholic fatty liver disease.
        Front Endocrinol. 2021; 12711956
        • Bril F.
        • Kadiyala S.
        • Portillo Sanchez P.
        • et al.
        Plasma thyroid hormone concentration is associated with hepatic triglyceride content in patients with type 2 diabetes.
        J Investig Med. 2016; 64: 63-68
        • Du J.
        • Chai S.
        • Zhao X.
        • et al.
        Association between thyroid hormone levels and advanced liver fibrosis in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease.
        Diabetes Metab Syndr Obes. 2021; 14: 2399-2406
        • Zhang Y.
        • Li J.
        • Liu H
        Correlation between the thyroid hormone levels and nonalcoholic fatty liver disease in type 2 diabetic patients with normal thyroid function.
        BMC Endocr Disord. 2022; 22: 144
        • Hansen D.
        • Bennedbaek F.N.
        • Hansen L.K.
        • et al.
        Thyroid function, morphology and autoimmunity in young patients with insulin-dependent diabetes mellitus.
        Eur J Endocrinol. 1999; 140: 512-518
        • Shi R.
        • Lin C.
        • Hong Y.
        • et al.
        Free triiodothyronine is independently associated with nonalcoholic fatty liver disease in hospitalized type 2 diabetes mellitus patients.
        Biomed Res Int. 2021; 20218868339
        • Eshraghian A.
        • Hamidian Jahromi A
        Non-alcoholic fatty liver disease and thyroid dysfunction: a systematic review.
        World J. Gastroenterol. 2014; 20: 8102-8109
        • Chung G.E.
        • Kim D.
        • Kwak M.S.
        • et al.
        Longitudinal change in thyroid-stimulating hormone and risk of nonalcoholic fatty liver disease.
        Clin Gastroenterol Hepatol. 2021; 19 (e1): 848-849
        • Liu J.
        • Ayada I.
        • Zhang X.
        • et al.
        Estimating global prevalence of metabolic dysfunction-associated fatty liver disease in overweight or obese adults.
        Clin Gastroenterol Hepatol. 2022; 20: e573-ee82
        • Guo Z.
        • Li M.
        • Han B.
        • et al.
        Association of non-alcoholic fatty liver disease with thyroid function: a systematic review and meta-analysis.
        Dig Liver Dis. 2018; 50: 1153-1162
        • Jaruvongvanich V.
        • Sanguankeo A.
        • Upala S
        Nonalcoholic fatty liver disease is not associated with thyroid hormone levels and hypothyroidism: a systematic review and meta-analysis.
        Eur Thyroid J. 2017; 6: 208-215
        • Sinha R.A.
        • Bruinstroop E.
        • Singh B.K.
        • et al.
        Nonalcoholic fatty liver disease and hypercholesterolemia: roles of thyroid hormones, metabolites, and agonists.
        Thyroid. 2019; 29: 1173-1191
        • Liu T.
        • Li Y.
        • Teng D.
        • et al.
        The characteristics of iodine nutrition status in china after 20 years of universal salt iodization: an epidemiology study covering 31 provinces.
        Thyroid. 2021; 31: 1858-1867
        • Shan Z.
        • Chen L.
        • Lian X.
        • et al.
        Iodine status and prevalence of thyroid disorders after introduction of mandatory universal salt iodization for 16 years in China: a cross-sectional study in 10 cities.
        Thyroid. 2016; 26: 1125-1130
        • Wang Z.
        • Zang J.
        • Shi Z.
        • et al.
        Iodine status of 8 to 10 years old children within 20 years following compulsory salt iodization policy in Shanghai, China.
        Nutr J. 2019; 18: 63