Nonalcoholic Fatty Liver Disease and Hypercholesterolemia: Roles of Thyroid Hormones, Metabolites, and Agonists.

Thyroid : Official Journal of the American Thyroid Association
Rohit A SinhaPaul M Yen

Abstract

Background: Thyroid hormones (THs) exert a strong influence on mammalian lipid metabolism at the systemic and hepatic levels by virtue of their roles in regulating circulating lipoprotein, triglyceride (TAG), and cholesterol levels, as well as hepatic TAG storage and metabolism. These effects are mediated by intricate sensing and feedback systems that function at the physiological, metabolic, molecular, and transcriptional levels in the liver. Dysfunction in the pathways involved in lipid metabolism disrupts hepatic lipid homeostasis and contributes to the pathogenesis of metabolic diseases, such as nonalcoholic fatty liver disease (NAFLD) and hypercholesterolemia. There has been strong interest in understanding and employing THs, TH metabolites, and TH mimetics as lipid-modifying drugs. Summary: THs regulate many processes involved in hepatic TAG and cholesterol metabolism to decrease serum cholesterol and intrahepatic lipid content. TH receptor β analogs designed to have less side effects than the natural hormone are currently being tested in phase II clinical studies for NAFLD and hypercholesterolemia. The TH metabolites, 3,5-diiodo-l-thyronine (T2) and T1AM (3-iodothyronamine), have different beneficial effects on lipid met...Continue Reading

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