Quick glance at 'metabolic dysfunction associated steatotic liver disease' therapeutics: Targets, trials, and trends

Figure 3 The nuclear thyroid hormone receptor β - retinoid X receptor heterodimer is physiologically activated by triiodothyronine (T3). Resmetirom, a liver-directed agonist of thyroid hormone receptor β (THRβ), interacts with the THRβ - retinoid X receptor heterodimer to activate the thyroid hormone response elements, resulting in selective messenger ribonucleoprotein (mRNA) transcription and protein translation. The resultant proteins promote mitophagy (the removal of damaged mitochondria), mitochondrial biogenesis, and mitochondrial fatty acid oxidation, allowing for improved clearance of free fatty acids. It suppresses hepatic de novo lipogenesis by downregulating sterol regulatory element-binding protein 1c, fatty acid synthase, and acetyl-CoA carboxylase 1. Additional proteins: Cytochrome P450, family 7, subfamily A, polypeptide 1 increases bile acid synthesis; hydroxymethylglutaryl-CoA reductase increases cholesterol synthesis; the low-density lipoprotein receptor increases hepatic low-density lipoproteins uptake. RXR: Retinoid X receptor; TRE: Thyroid hormone response elements; LDL: Low-density lipoproteins; LDL-R: Low-density lipoprotein receptor; THRβ: Thyroid hormone receptor β.