title: Effect of High Glucose Concentration on Human Preadipocytes and Their Response to Macrophage-Conditioned Medium.
abstract: OBJECTIVE
  Adipose tissue expands via differentiation of preadipocytes into adipocytes (adipogenesis) and/or hypertrophy of existing adipocytes. A low adipogenic capacity promotes adipocyte hypertrophy, causing inflammatory macrophage accumulation and insulin resistance. Macrophage-conditioned medium (MacCM) inhibits adipogenesis and promotes adipocyte inflammation, but it is unknown whether these effects are altered by high glucose (HG) versus normal glucose (NG) concentrations. Our aim was to compare the effect of HG-MacCM versus NG-MacCM on human adipogenesis and adipocyte inflammation.
  
  
  METHODS
  Human monocyte-derived macrophages (MDMs) were placed in 5 mmol/L (NG) or 25 mmol/L (HG) glucose for 24 hours. MacCM was collected and its effect on differentiation of human subcutaneous abdominal preadipocytes and adipocyte inflammation was evaluated.
  
  
  RESULTS
  HG-MacCM, but not NG-MacCM, inhibited triacylglycerol (TG) accumulation and protein expression of peroxisome proliferator-activated receptor γ (PPARgamma) during human adipogenesis. Preadipocytes differentiated in HG-MacCM displayed a more pro-inflammatory phenotype, as assessed by increased interleukin-6 and monocyte chemotactic protein-1 (MCP-1), as well as reduced adiponectin mRNA expression. In MDMs, HG increased phosphorylation of inhibitor of kappaB kinase (IKK)-beta and decreased protein expression of inhibitor of kappaB alpha. HG also reduced protein expression of PPARgamma in MDMs. However, no MDM changes in mRNA expression of MCP-1, interleukin-1beta or tumor necrosis factor-alpha were detected. The stimulatory effect of HG-MacCM on MCP-1 expression in adipocytes was partially inhibited when MDMs were treated with sc-514 (IKKbeta inhibitor).
  
  
  CONCLUSIONS
  High glucose concentration accentuates the anti-adipogenic and pro-inflammatory effects of MacCM on human preadipocytes.
authors.affiliation: Chronic Disease Program, Ottawa Hospital Research Institute, Departments of Medicine and Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Vian
authors.initials: V
authors.lastname: Peshdary
authors.affiliation: Chronic Disease Program, Ottawa Hospital Research Institute, Departments of Medicine and Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: AnneMarie
authors.initials: A
authors.lastname: Gagnon
authors.affiliation: Chronic Disease Program, Ottawa Hospital Research Institute, Departments of Medicine and Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada. Electronic address: asorisky@ohri.ca.
authors.forename: Alexander
authors.initials: A
authors.lastname: Sorisky
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects* / Q000276:immunology; D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000502:physiology; D008297:Male; D008875:Middle Aged
chemical_list: D017077:Culture Media, Conditioned; D005947:Glucose
keywords: adipocyte; adipogenesis; adipogenèse; glucose; inflammation; macrophage; preadipocyte; préadipocyte