NAFLD and thyroid function: pathophysiological and therapeutic considerations

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a worldwide rising challenge because of hepatic, but also extrahepatic, complications. Thyroid hormones are master regulators of energy and lipid homeostasis, and the presence of abnormal thyroid function in NAFLD suggests pathogenic relationships. Specifically, persons with hypothyroidism feature dyslipidemia and lower hepatic β-oxidation, which favors accumulation of triglycerides and lipotoxins, insulin resistance, and subsequently de novo lipogenesis. Recent studies indicate that liver-specific thyroid hormone receptor β agonists are effective for the treatment of NAFLD, likely due to improved lipid homeostasis and mitochondrial respiration, which, in turn, may contribute to a reduced risk of NAFLD progression. Taken together, the possible coexistence of thyroid disease and NAFLD calls for increased awareness and optimized strategies for mutual screening and management.

Keywords: hypothyroidism; nonalcoholic fatty liver disease; resmetirom; thyroxine; triglycerides; triiodothyronine.