Hypothyroidism-Induced Nonalcoholic Fatty Liver Disease (HIN): Mechanisms and Emerging Therapeutic Options

Abstract

Nonalcoholic fatty liver disease (NAFLD) is an emerging worldwide problem and its association with other metabolic pathologies has been one of the main research topics in the last decade. The aim of this review article is to provide an up-to-date correlation between hypothyroidism and NAFLD. We followed evidence regarding epidemiological impact, immunopathogenesis, thyroid hormone-liver axis, lipid and cholesterol metabolism, insulin resistance, oxidative stress, and inflammation. After evaluating the influence of thyroid hormone imbalance on liver structure and function, the latest studies have focused on developing new therapeutic strategies. Thyroid hormones (THs) along with their metabolites and thyroid hormone receptor β (THR-β) agonist are the main therapeutic targets. Other liver specific analogs and alternative treatments have been tested in the last few years as potential NAFLD therapy. Finally, we concluded that further research is necessary as well as the need for an extensive evaluation of thyroid function in NAFLD/NASH patients, aiming for better management and outcome.

Keywords: hypothyroidism; nonalcoholic fatty liver disease (NAFLD); thyromimetics.

Figure 1

The complex relationship of hypothyroidism-induced NAFLD (HIN). Thyroid stimulating hormone (TSH); free thyroxine (fT4); free triiodothyronine (fT3); de novo lipogenesis (DNL); free fatty acids (FFAs); lipoprotein lipase (LPL); triglycerides (TG); AMP-activated protein kinase (AMPK); sterol regulatory element-binding protein (SREBP-1c); tumor necrosis factor alpha (TNF-α).