Monocyte chemoattractant protein-1 and nitric oxide promote adipogenesis in a model that mimics obesity.
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.
Hemmrich
Karsten
K
Bernard O'Brien Institute of Microsurgery, Fitzroy, Victoria, Australia. hemmrich@gmx.de
Thomas
Gregory P L
GP
Abberton
Keren M
KM
Thompson
Erik W
EW
Rophael
John A
JA
Penington
Anthony J
AJ
Morrison
Wayne A
WA
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
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