Endocrinol Metab.  2024 Oct;39(5):686-692. 10.3803/EnM.2024.2068.

Thyroid Hormone-Mediated Selective Autophagy and Its Implications in Countering Metabolic Dysfunction-Associated Steatotic Liver Disease

• Sinha RA

• KMID: 2560275
• DOI: http://doi.org/10.3803/EnM.2024.2068

Abstract

The influence of thyroid hormone (TH) on liver metabolism has attracted the attention of pharmacologists seeking new treatments for metabolic dysfunction-associated steatotic liver disease (MASLD), an increasingly common metabolic disorder. In this context, the selective induction of autophagy by TH in preclinical models has been identified as a promising mechanism. In this process, TH clears intrahepatic fat through lipophagy while protecting against inflammation and mitochondrial damage in hepatocytes via mitophagy. Furthermore, TH-induced aggrephagy may represent a protective mechanism to mitigate the development of MASLD-associated hepatocellular carcinoma. Considering the defects in autophagy observed during the progression of human MASLD, the induction of autophagy by TH, its metabolites, and its analogs represent a novel strategy to combat hepatic damage across the MASLD spectrum.

Keyword

Metabolic dysfunction-associated steatotic liver disease; Thyroid hormones; Autophagy; Mitophagy; 3,5-Diiodothyronine; Resmetirom; Metabolic dysfunction-associated steatohepatitis; MASLD-associated hepatocellular carcinoma