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Adipocyte-derived serum amyloid A3 and hyaluronan play a role in monocyte recruitment and adhesion

¹Departments of Medicine, University of Washington, and
²Hope Heart Program, Benaroya Research Institute, Seattle, Washington

Correspondence: achait{at}u.washington.edu

OBJECTIVES: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 (HA) 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.

RESEARCH DESIGN AND METHODS:Differentiated 3T3-L1 adipocytes made hypertrophic by growth in high glucose conditions were used to study SAA and HA regulation in vitro. Two mouse models of obesity were used to study their expression in vivo.

RESULTS:NFB was upregulated and PPAR was downregulated in hypertrophic 3T3-L1 cells, with increased expression of SAA3 and increased HA production. Rosiglitazone, a PPAR 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 HA existed as part of a complex matrix, which increased the adhesion and retention of monocytes. This complex, purified by binding to a biotinylated hyaluronan binding protein (HABP) affinity column, also showed monocyte chemotactic activity, which was dependent on the presence of both SAA3 and HA but independent of MCP-1.

CONCLUSIONS:We hypothesize that adipocyte hypertrophy leads to increased production of SAA and HA, which act in concert to recruit and retain monocytes, thereby leading to local inflammation in adipose tissue.

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