Adipocyte-derived serum amyloid A3 and hyaluronan play a role in monocyte recruitment and adhesion.
Obesity is characterized by adipocyte hypertrophy and macrophage accumulation in adipose tissue. Monocyte chemoattractant protein-1 (MCP-1) plays a role in macrophage recruitment into adipose tissue. However, other adipocyte-derived factors, e.g., hyaluronan and serum amyloid A (SAA), can facilitate monocyte adhesion and chemotaxis, respectively. The objective was to test the potential involvement of these factors in macrophage recruitment. Differentiated 3T3-L1 adipocytes made hypertrophic by growth in high glucose conditions were used to study SAA and hyaluronan regulation in vitro. Two mouse models of obesity were used to study their expression in vivo. Nuclear factor-kappaB was upregulated and peroxisome proliferator-activated receptor (PPAR)gamma was downregulated in hypertrophic 3T3-L1 cells, with increased expression of SAA3 and increased hyaluronan production. Rosiglitazone, a PPARgamma agonist, reversed these changes. Hypertrophic adipocytes demonstrated overexpression of SAA3 and hyaluronan synthase 2 in vitro and in vivo in diet-induced and genetic obesity. SAA and hyaluronan existed as part of a complex matrix that increased the adhesion and retention of monocytes. This complex, purified by binding to a biotinylated hyaluronan binding protein affinity column, also showed monocyte chemotactic activity, which was dependent on the presence of SAA3 and hyaluronan but independent of MCP-1. We hypothesize that adipocyte hypertrophy leads to increased production of SAA and hyaluronan, which act in concert to recruit and retain monocytes, thereby leading to local inflammation in adipose tissue.
Han
Chang Yeop
CY
Department of Medicine, University of Washington, Seattle, Washington 98195-6426, USA.
Subramanian
Savitha
S
Chan
Christina K
CK
Omer
Mohamed
M
Chiba
Tsuyoshi
T
Wight
Thomas N
TN
Chait
Alan
A
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000273:Adipose Tissue / Q000503:physiopathology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics*; D005947:Glucose / Q000494:pharmacology*; D006820:Hyaluronic Acid / Q000378:metabolism*; D007249:Inflammation; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism / Q000502:physiology; D000077154:Rosiglitazone; D000685:Serum Amyloid A Protein / Q000235:genetics*; D045162:Thiazolidinediones / Q000494:pharmacology
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016328:NF-kappa B; D047495:PPAR gamma; C076498:Saa3 protein, mouse; D000685:Serum Amyloid A Protein; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D006820:Hyaluronic Acid; D005947:Glucose