title: Monocyte chemoattractant protein-1 and nitric oxide promote adipogenesis in a model that mimics obesity.
abstract: OBJECTIVE
  An increasing body of evidence is emerging linking adipogenesis and inflammation. Obesity, alone or as a part of the metabolic syndrome, is characterized by a state of chronic low-level inflammation as revealed by raised plasma levels of inflammatory cytokines and acute-phase proteins. If inflammation can, in turn, increase adipose tissue growth, this may be the basis for a positive feedback loop in obesity. We have developed a tissue engineering model for growing adipose tissue in the mouse that allows quantification of increases in adipogenesis. In this study, we evaluated the adipogenic potential of the inflammogens monocyte chemoattractant protein (MCP)-1 and zymosan-A (Zy) in a murine tissue engineering model.
  
  
  METHODS
  MCP-1 and Zy were added to chambers filled with Matrigel and fibroblast growth factor 2. To analyze the role of inducible nitric oxide synthase (iNOS), the iNOS inhibitor aminoguanidine was added to the chamber.
  
  
  RESULTS
  Our results show that MCP-1 generated proportionally large quantities of new adipose tissue. This neoadipogenesis was accompanied by an ingrowth of macrophages and could be mimicked by Zy. Aminoguanidine significantly inhibited the formation of adipose tissue.
  
  
  CONCLUSIONS
  Our findings demonstrate that low-grade inflammation and iNOS expression are important factors in adipogenesis. Because fat neoformation in obesity and the metabolic syndrome is believed to be mediated by macrophage-derived proinflammatory cytokines, this adipose tissue engineering system provides a model that could potentially be used to further unravel the pathogenesis of these two metabolic disorders.
authors.affiliation: Bernard O'Brien Institute of Microsurgery, Fitzroy, Victoria, Australia. hemmrich@gmx.de
authors.forename: Karsten
authors.initials: K
authors.lastname: Hemmrich
authors.forename: Gregory P L
authors.initials: GP
authors.lastname: Thomas
authors.forename: Keren M
authors.initials: KM
authors.lastname: Abberton
authors.forename: Erik W
authors.initials: EW
authors.lastname: Thompson
authors.forename: John A
authors.initials: JA
authors.lastname: Rophael
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Penington
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Morrison
mesh_terms: D050156:Adipogenesis / Q000187:drug effects*; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D018932:Chemokine CCL2 / Q000494:pharmacology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000473:pathology*; D023822:Tissue Engineering / Q000379:methods; D015054:Zymosan / Q000494:pharmacology
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D006146:Guanidines; D009569:Nitric Oxide; D015054:Zymosan; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine