Role of serum amyloid a in adipocyte-macrophage cross talk and adipocyte cholesterol efflux.

CONTEXT

Acute phase serum amyloid A (A-SAA) is secreted by hepatocytes in response to injury and is regulated by proinflammatory cytokines. In obese humans, adipocytes are also a major contributor to circulating A-SAA levels.

OBJECTIVE

We aimed to investigate the role and regulation of A-SAA in human adipose tissue (AT).

DESIGN

An approach combining microarrays and the FunNet bioinformatics tool was applied to human AT fractions (i.e. adipocytes vs. stroma vascular fraction) to hypothesize genes and functions related to A-SAA. Experiments with human AT from 37 obese subjects and human multipotent adipose-derived stem (hMADS) cells were used to confirm the microarray driven hypotheses.

RESULTS

Microarray analysis highlighted the relationship between A-SAA and stroma vascular fraction inflammatory genes, and between A-SAA and adipocyte-expressed ATP-binding cassette (ABC) transporters. We confirmed that serum amyloid A (SAA) protein is expressed in sc AT of obese subjects (n = 37, body mass index = 49.3 +/- 1.5 kg/m(2)) and showed that SAA protein expression correlated with adipocyte size (R = 0.44; P = 6.10(-3)), macrophage infiltration (R = 0.61; P = 10(-4)), and ABC subfamily A1 protein expression (R = 0.43; P = 9.10(-3)). IL-1beta, TNF-alpha, and human AT macrophage-conditioned medium significantly induced A-SAA secretion (from 2.6 to 7.6 fold) in hMADS cells. Recombinant SAA induced cholesterol ABC subfamily A1-dependent efflux from hMADS adipocytes by 4.3-fold in a dose-dependent manner.

CONCLUSION

This work provides original insight suggesting that A-SAA is a player in the dialogue between hypertrophied adipocytes and macrophages through its regulation of adipocyte cholesterol efflux.