Fig. 2

Mechanism of action for thyroid hormones in the liver. Sources of intrahepatic FFAs: 1. Extrahepatic FFAs enter hepatocytes via transport proteins, such as FATPs, L-FABPs, and CD36. T₃ promotes the expression of these transport proteins. 2. Glucose is converted into FFA through the DNL pathway by enzymes, such as FAS and ACC, and T₃ promotes the expression of related enzymes. 3. Hepatic lipase and AGTL break down triglycerides into FFAs and T₃ promotes the expression of related enzymes. 4. Lysosomes are involved in lipophagy, which breaks down triglycerides into FFAs. T₃ increases lysosomal biogenesis, improves LAMP expression, and increases lysosomal stability. Destinations of FFAs in the liver: 5. Conversion to triglycerides stored in the liver by FAS and ACC, and T₃ promotes the expression of related enzymes. 6. Involved in β-oxidation in mitochondria and eventually metabolized. T₃ increases mitochondrial biogenesis, promotes the expression of β-oxidation related rate-limiting enzymes, and facilitates autophagic degradation of damaged mitochondria to maintain the quality of mitochondria at a high level. 7. Conversion to cholesterol, where LDL is converted into bile acids or excreted directly into the bile. T₃ promotes the expression of rate-limiting enzymes and LDL-R during cholesterol synthesis. ABCG, a transporter protein required for the transfer of bile acids and part of the cholesterol into bile, is also upregulated by T₃