Please use this identifier to cite or link to this item:
Title: Early induction of hepatic deiodinase type 1 inhibits hepatosteatosis during NAFLD progression
Authors: Bruinstroop, E 
Zhou, J 
Tripathi, M 
Yau, WW 
Boelen, A
Singh, BK 
Yen, PM 
Keywords: Deiodinase
Cells, Cultured
Iodide Peroxidase
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Non-alcoholic Fatty Liver Disease
Issue Date: 1-Nov-2021
Publisher: Elsevier BV
Citation: Bruinstroop, E, Zhou, J, Tripathi, M, Yau, WW, Boelen, A, Singh, BK, Yen, PM (2021-11-01). Early induction of hepatic deiodinase type 1 inhibits hepatosteatosis during NAFLD progression. Molecular Metabolism 53 : 101266-. ScholarBank@NUS Repository.
Abstract: Objective: 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. Methods: 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. Results: 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 ratio and acylcarnitine levels, suggesting there was lower β-oxidation. Dio1 siRNA KD in hepatic cells treated with fatty acids showed increased lipid accumulation and decreased oxidative phosphorylation. Conclusion: Hepatic Dio1 gene expression was modulated by dietary conditions, was increased during hepatosteatosis and early NASH, and regulated hepatic triglyceride content. These early adaptations likely represent compensatory mechanisms that reduce hepatosteatosis and prevent NASH progression.
Source Title: Molecular Metabolism
ISSN: 22128778
DOI: 10.1016/j.molmet.2021.101266
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
Early induction of hepatic deiodinase type 1 inhibits hepatosteatosis during NAFLD progression.pdfPublished version1.59 MBAdobe PDF




checked on Sep 23, 2022

Page view(s)

checked on Sep 22, 2022


checked on Sep 22, 2022

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.