Mechanisms of hepatic steatosis in mice fed a lipogenic methionine choline-deficient diet

Mary E. Rinella, Marc S. Elias, Robin R. Smolak, Tao Fu, Jayme Borensztajn, Richard M. Green

Research output: Contribution to journalArticlepeer-review

271 Scopus citations

Abstract

The methionine choline-deficient (MCD) diet results in liver injury similar to human nonalcoholic steatohepatitis (NASH). The aims of this study were to define mechanisms of MCD-induced steatosis in insulin-resistant db/db and insulin-sensitive db/m mice. MCD-fed db/db mice developed more hepatic steatosis and retained more insulin resistance than MCD-fed db/m mice. Both subcutaneous and gonadal fat were reduced by MCD feeding: gonadal fat decreased by 23% in db/db mice and by 90% in db/m mice. Weight loss was attenuated in the db/db mice, being only 13% compared with 35% in MCD-fed db/db and db/m mice, respectively. Both strains had upregulation of hepatic fatty acid transport proteins as well as increased hepatic uptake of [ 14C]oleic acid: 3-fold in db/m mice (P <0.001) and 2-fold in db/db mice (P < 0.01) after 4 weeks of MCD feeding. In both murine strains, the MCD diet reduced triglyceride secretion and downregulated genes involved in triglyceride synthesis. Therefore, increased fatty acid uptake and decreased VLDL secretion represent two important mechanisms by which the MCD diet promotes intrahepatic lipid accumulation in this model. Feeding the MCD diet to diabetic rodents broadens the applicability of this model for the study of human NASH.

Original languageEnglish (US)
Pages (from-to)1068-1076
Number of pages9
JournalJournal of lipid research
Volume49
Issue number5
DOIs
StatePublished - May 1 2008

Keywords

  • Db/db mouse
  • Lipid metabolism
  • Nonalcoholic steatohepatitis
  • Visceral fat

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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