Early induction of hepatic deiodinase type 1 inhibits hepatosteatosis during NAFLD progression.

Molecular Metabolism
Eveline BruinstroopP. M. Yen

Abstract

Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum ranging from hepatosteatosis to progressive nonalcoholic steatohepatitis that can lead to cirrhosis. Humans with low levels of prohormone thyroxine (T4) have a higher incidence of NAFLD, and thyroid hormone treatment is very promising in all patients with NAFLD. Deiodinase type 1 (Dio1) is a hepatic enzyme that converts T4 to the bioactive T3 and therefore regulates thyroid hormone availability within hepatocytes. We investigated the role of this intrahepatic regulation during the progression of NAFLD. We investigated hepatic thyroid hormone metabolism in two NAFLD models: wild-type mice fed a Western diet with fructose and Leprdb mice fed a methionine- and choline-deficient diet. AAV8-mediated liver-specific Dio1 knockdown was employed to investigate the role of Dio1 during the progression of NAFLD. Intrahepatic thyroid hormone levels, deiodinase activity, and metabolic parameters were measured. Dio1 expression and activity were increased in the early stages of NAFLD and were associated with an increased T3/T4 ratio. Prevention of this increase by AAV8-mediated liver-specific Dio1 knockdown increased hepatic triglycerides and cholesterol and decreased the pACC/ACC r...Continue Reading

References

May 22, 2008·The Journal of Clinical Endocrinology and Metabolism·Vijay PanickerTimothy M Frayling
Dec 17, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Edward E CableMark D Erion
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Aug 14, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Rafal P WitekAnna Mae Diehl
Jun 12, 2012·The Journal of Clinical Investigation·Rohit Anthony SinhaPaul M Yen
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May 7, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Jing LiuHenry N Ginsberg
Jan 29, 2017·The Journal of Endocrinology·Anita BoelenEric Fliers
May 3, 2018·The Journal of Clinical Endocrinology and Metabolism·Eveline BruinstroopPaul M Yen
Aug 8, 2019·Thyroid : Official Journal of the American Thyroid Association·Rohit A SinhaPaul M Yen
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