Understanding the Relationship between Nonalcoholic Fatty Liver Disease and Thyroid Disease

The prevalence of hypothyroidism in patients with nonalcoholic fatty liver disease (NAFLD) is high (22.4%). Thyroid hormones (THs) regulate many metabolic activities in the liver by promoting the export and oxidation of lipids, as well as de novo lipogenesis. They also control hepatic insulin sensitivity and suppress hepatic gluconeogenesis. Because of its importance in lipid and carbohydrate metabolism, the involvement of thyroid dysfunction in the pathogenesis of NAFLD seems plausible. The mechanisms implicated in this relationship include high thyroid-stimulating hormone (TSH) levels, low TH levels, and chronic inflammation. The activity of the TH receptor (THR)-beta in response to THs is essential in the pathogenesis of hypothyroidism-induced NAFLD. Therefore, an orally active selective liver THR-beta agonist, Resmetirom (MGL-3196), was developed, and has been shown to reduce liver fat content, and as a secondary end point, to improve nonalcoholic steatohepatitis. The treatment of NAFLD with THR-beta agonists seems quite promising, and other agonists are currently under development and investigation. This review aims to shine a light on the pathophysiological and epidemiological evidence regarding this relationship and the effect that treatment with THs and selective liver THR-beta agonists have on hepatic lipid metabolism.

Automated summary

The high prevalence of hypothyroidism in NAFLD patients suggests a possible involvement of thyroid dysfunction in the pathogenesis of NAFLD. Thyroid hormones regulate lipid and carbohydrate metabolism in the liver, and selective liver THR-beta agonists have shown promise in reducing liver fat content and improving nonalcoholic steatohepatitis.