title: Chlamydophila pneumoniae inhibits differentiation of progenitor adipose cells and impairs insulin signaling.
abstract: BACKGROUND
  Recent clinical studies have shown Chlamydophila pneumoniae seropositivity to be related to overweight status and inversely related to insulin sensitivity. The present study was performed to investigate the potential effects of C. pneumoniae infection of adipocytes.
  
  
  METHODS
  3T3-L1 cells and primary epididymal preadipocytes were infected with C. pneumoniae either before or after induction of differentiation, and the effects on adipogenesis and insulin signaling were determined. Tumor necrosis factor (TNF)-alpha signaling was examined by assessing the effects of C. pneumoniae infection in preadipocytes isolated from epididymal adipose tissue of both wild-type and TNF-alpha(-/-) mice.
  
  
  RESULTS
  C. pneumoniae successfully infected both undifferentiated and differentiated 3T3-L1 cells in vitro. The bacteria were also detected in adipose tissue of infected low-density lipoprotein receptor-deficient mice. TNF-alpha protein levels were significantly increased in cells infected with either live or heat-killed C. pneumoniae or treated with lipopolysaccharide or heat-shock protein 65; this increase was associated with inhibition of adipocyte differentiation and down-regulation of insulin-stimulated tyrosine-phosphorylated insulin receptor and its substrate. In contrast, C. pneumoniae infection in TNF-alpha(-/-) adipocytes produced no apparent changes, but addition of recombinant TNF-alpha reversed this effect.
  
  
  CONCLUSIONS
  We demonstrate for the first time that C. pneumoniae can infect murine pre- and postdifferentiated adipocytes and, through a TNF-alpha-mediated inflammatory mechanism, can impair differentiation and insulin signaling.
authors.affiliation: Toronto General Hospital Research Institute, Toronto, Ontario, Canada.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shi
authors.forename: Youan
authors.initials: Y
authors.lastname: Liu
authors.forename: Andrew
authors.initials: A
authors.lastname: Murdin
authors.forename: Ausra
authors.initials: A
authors.lastname: Raudonikiene-Mancevski
authors.forename: Bilal B
authors.initials: BB
authors.lastname: Ayach
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Yu
authors.forename: I George
authors.initials: IG
authors.lastname: Fantus
authors.forename: Peter P
authors.initials: PP
authors.lastname: Liu
mesh_terms: D016475:3T3 Cells; D000273:Adipose Tissue / Q000166:cytology* / Q000382:microbiology*; D000818:Animals; D017304:Annexin A5 / Q000032:analysis; D002454:Cell Differentiation / Q000502:physiology*; D016993:Chlamydophila pneumoniae / Q000302:isolation & purification / Q000472:pathogenicity / Q000502:physiology*; D006367:HeLa Cells / Q000166:cytology; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D015398:Signal Transduction
chemical_list: D017304:Annexin A5; D007328:Insulin