title: Murine gamma herpes virus 68 infection promotes fatty liver formation and hepatic insulin resistance in C57BL/6J mice.
abstract: OBJECTIVE
  Murine gamma herpes virus 68 (MHV68) is a naturally occurring mouse pathogen that is homologous to Epstein-Barr virus. This study was designed to determine the correlation between MHV68 infection and lipid accumulation and insulin resistance in livers of C57BL/6J mice, and to explore the underlying mechanisms.
  
  
  METHODS
  C57BL/6J mice fed a high fat diet were randomly assigned to receive either MHV68 or phosphate buffered saline treatment. Insulin sensitivities were evaluated by glucose tolerance tests. Serum was analyzed for lipids and cytokines. Liver was taken for histology and lipid analysis. Quantitative RT-PCR and western blotting were used to measure expression of hepatic mammalian target of rapamycin (mTOR), ribosomal S6 kinase 1 (S6K1), insulin receptor substrate-1 (IRS-1), sterol regulatory element binding protein-1 (SREBP1), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC).
  
  
  RESULTS
  MHV68 infection promoted fatty liver, hypertriglyceridemia, insulin resistance, and hyperinsulinemia in association with elevated inflammatory cytokines. In the livers of MHV68-infected C57BL/6J mice, SREBP1, FAS, ACC levels were increased. MHV68 infection also inhibited total IRS-1 expression and increased serine phosphorylation levels of IRS-1, which is parallel to the over activation of mTOR signaling pathway. Sirolimus, a specific inhibitor of mTOR pathway, inhibited MHV68-induced hepatic expression of serine p-IRS-1, increased total IRS-1 levels and improved MHV68-induced hepatic insulin resistance.
  
  
  CONCLUSIONS
  In C57BL/6J mice, MHV68 infection promotes fatty liver formation and hepatic insulin resistance, which can be ameliorated by sirolimus.
authors.affiliation: Centre for Lipid Research, Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Centre for Lipid Research, Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Ya-Xi
authors.initials: YX
authors.lastname: Chen
authors.affiliation: Lipid Research Unit, Centre for Nephrology, University College London (UCL) Medical School, Royal Free Campus, University College London, London, UK.
authors.forename: Zac
authors.initials: Z
authors.lastname: Varghese
authors.affiliation: Centre for Lipid Research, Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Ai-Long
authors.initials: AL
authors.lastname: Huang
authors.affiliation: Centre for Lipid Research, Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Ren-Kuan
authors.initials: RK
authors.lastname: Tang
authors.affiliation: Centre for Lipid Research, Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Bei
authors.initials: B
authors.lastname: Jia
authors.affiliation: Lipid Research Unit, Centre for Nephrology, University College London (UCL) Medical School, Royal Free Campus, University College London, London, UK.
authors.forename: John F
authors.initials: JF
authors.lastname: Moorhead
authors.affiliation: Centre for Lipid Research, Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Gong
authors.affiliation: Centre for Lipid Research, Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China. x.ruan@medsch.ucl.ac.uk.|Lipid Research Unit, Centre for Nephrology, University College London (UCL) Medical School, Royal Free Campus, University College London, London, UK. x.ruan@medsch.ucl.ac.uk.
authors.forename: Xiong Z
authors.initials: XZ
authors.lastname: Ruan