Thyroid hormone signaling promotes hepatic lipogenesis through the transcription factor ChREBP

Abstract

The transcription factor ChREBP mediates lipid accumulation in the liver in response to thyroid hormone.

Sensitivity to thyroid hormones is associated with advanced fibrosis in euthyroid patients with non-alcoholic fatty liver disease: A cross-sectional study

“…THs have profound effects on stimulating lipolysis to generate free fatty acids (FFAs) and regulate FFA uptake in the liver [24] . Additionally, THs can stimulate DNL in the liver by upregulating the expression of the main genes involved in lipogenesis [25] . Moreover, THs can help regulate serum concentrations of cholesterol by increasing the biosynthesis, export, reverse transport, and conversion of cholesterol into bile acids [26] .…”

Hepatic Energy Metabolism under the Local Control of the Thyroid Hormone System

“…However, Chrebp-KO showed decreased hepatic TG concentrations during hyperthyroidism and increased concentrations in a hypothyroid situation, compared to WT. The authors proposed as an underlying mechanism that the increased hepatic TG content in the Chrebp-KO model in hypothyroidism is related to decreased export of VLDL from the liver, whereas in the hyperthyroid animals, the decreased FAO results from lowered availability of substrates and cofactors from DNL [106]. Downstream of the previously described TRß1-specific activation of Sirt1, the master regulator of lipogenesis, Pgc1a is activated.…”

Effects of the Pituitary-targeted Gland Axes on Hepatic Lipid Homeostasis in Endocrine-associated Fatty Liver Disease-A Concept Worth Revisiting

“…Thyroid hormones fine-tune hepatic lipogenesis via modulation of both SREBP-1 and carbohydrate response element-binding protein (ChREBP) gene expression, 16 and these effects are likely to be mediated through the activation of TRβ in the liver and adipocytes. 17 Although similar to the effect of T3 on hepatic lipids, 3,5-diiodo-l-thyronine (T2), the metabolite of triiodothyronine (T3), acts by increasing hepatic nuclear sirtuin 1 (SIRT1) activity rather than TRβ, mainly targeting peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC-1α) and SREBP-1c, resulting in the downregulation of lipogenic genes. 16 , 18 This evidence makes T2 a potential selective agent for the treatment of NAFLD under specific metabolic conditions.…”