Hepatic Inactivation of the Type 2 Deiodinase Confers Resistance to Alcoholic Liver Steatosis

Tatiana L. Fonseca, Gustavo W. Fernandes, Barbara M.L.C. Bocco, Ali Keshavarzian, Shriram Jakate, Terrence M. Donohue, Balázs Gereben, Antonio C. Bianco

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: A mouse with hepatocyte-specific deiodinase type II inactivation (Alb-D2KO) is resistant to diet-induced obesity, hepatic steatosis, and hypertriglyceridemia due to perinatal epigenetic modifications in the liver. This phenotype is linked to low levels of Zfp125, a hepatic transcriptional repressor that promotes liver steatosis by inhibiting genes involved in packaging and secretion of very-low-density lipoprotein. Methods: Here, we used chronic and binge ethanol (EtOH) in mice to cause liver steatosis. Results: The EtOH treatment causes a 2.3-fold increase in hepatic triglyceride content; Zfp125 levels were approximately 50% higher in these animals. In contrast, Alb-D2KO mice did not develop EtOH-induced liver steatosis. They also failed to elevate Zfp125 to the same levels, despite being on the EtOH-containing diet for the same period of time. Their phenotype was associated with 1.3- to 2.9-fold up-regulation of hepatic genes involved in lipid transport and export that are normally repressed by Zfp125, that is, Mttp, Abca1, Ldlr, Apoc1, Apoc3, Apoe, Apoh, and Azgp1. Furthermore, genes involved in the EtOH metabolic pathway, that is, Aldh2 and Acss2, were also 1.6- to 3.1-fold up-regulated in Alb-D2KO EtOH mice compared with control animals kept on EtOH. Conclusions: EtOH consumption elevates expression of Zfp125. Alb-D2KO animals, which have lower levels of Zfp125, are much less susceptible to EtOH-induced liver steatosis.

Original languageEnglish (US)
Pages (from-to)1376-1383
Number of pages8
JournalAlcoholism: Clinical and Experimental Research
Volume43
Issue number7
DOIs
StatePublished - Jul 2019

Keywords

  • Deiodinase
  • Ethanol
  • Lipogenesis
  • Liver
  • Steatosis
  • Thyroid Hormone

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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