Progressive intrahepatic hypothyroidism has been well recognized to play a role in liver disease since 1975.1-3

Thyroid hormone signaling impairment worsens hepatic lipotoxicity, driving progression of metabolic dysfunction–associated steatotic liver disease (MASLD) to MASH with liver fibrosis.4

In MASH in humans, the liver has low THR-β activity, exacerbating mitochondrial dysfunction, lipotoxicity, and fibrosis.5

THR-β agonists act on multiple hepatic pathways to maintain liver health by controlling:6

  • Fatty acid oxidation
  • Mitophagy and mitochondrial biogenesis
  • Cholesterol metabolism
  • Direct anti-inflammatory and anti-fibrotic effects7

MASH and the role of the THR-β pathway

  1. Nomura S, et al. JCI. 1975;56(3):643.
  2. Karim G, Bansal MB. touchREV Endocrinol. 2023;19(1):60-70.
  3. Peeters RP, et al. J Clin Endocrinol Metab. 2003;88(7):3202-11.
  4. Chaves C, et al. Thyroid. 2021;31(7):1127-1134.
  5. Krause C, et al. Endocr Connect. 2018;7(12):1448-1456.
  6. Sinha RA, et al. Nat Rev Endocrinol. 2018;14(5):259-269.
  7. Alonso-Merino E, et al. Proc Natl Acad Sci USA. 2016;113(24):E3451-E3460.