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Acute-phase serum amyloid A: an inflammatory adipokine and potential link between obesity and its metabolic complications.

Abstract：

BACKGROUND:Obesity is associated with low-grade chronic inflammation, and serum markers of inflammation are independent risk factors for cardiovascular disease (CVD). However, the molecular and cellular mechanisms that link obesity to chronic inflammation and CVD are poorly understood. METHODS AND FINDINGS:Acute-phase serum amyloid A (A-SAA) mRNA levels, and A-SAA adipose secretion and serum levels were measured in obese and nonobese individuals, obese participants who underwent weight-loss, and persons treated with the insulin sensitizer rosiglitazone. Inflammation-eliciting activity of A-SAA was investigated in human adipose stromal vascular cells, coronary vascular endothelial cells and a murine monocyte cell line. We demonstrate that A-SAA was highly and selectively expressed in human adipocytes. Moreover, A-SAA mRNA levels and A-SAA secretion from adipose tissue were significantly correlated with body mass index (r = 0.47; p = 0.028 and r = 0.80; p = 0.0002, respectively). Serum A-SAA levels decreased significantly after weight loss in obese participants (p = 0.006), as well as in those treated with rosiglitazone (p = 0.033). The magnitude of the improvement in insulin sensitivity after weight loss was significantly correlated with decreases in serum A-SAA (r = -0.74; p = 0.034). SAA treatment of vascular endothelial cells and monocytes markedly increased the production of inflammatory cytokines, e.g., interleukin (IL)-6, IL-8, tumor necrosis factor alpha, and monocyte chemoattractant protein-1. In addition, SAA increased basal lipolysis in adipose tissue culture by 47%. CONCLUSIONS:A-SAA is a proinflammatory and lipolytic adipokine in humans. The increased expression of A-SAA by adipocytes in obesity suggests that it may play a critical role in local and systemic inflammation and free fatty acid production and could be a direct link between obesity and its comorbidities, such as insulin resistance and atherosclerosis. Accordingly, improvements in systemic inflammation and insulin resistance with weight loss and rosiglitazone therapy may in part be mediated by decreases in adipocyte A-SAA production.

journal_name

PLoS Med

journal_title

PLoS medicine

authors

Yang RZ,Lee MJ,Hu H,Pollin TI,Ryan AS,Nicklas BJ,Snitker S,Horenstein RB,Hull K,Goldberg NH,Goldberg AP,Shuldiner AR,Fried SK,Gong DW

doi

10.1371/journal.pmed.0030287

subject

Has Abstract

pub_date

2006-06-01 00:00:00

pages

e287

issue

eissn

1549-1277

issn

1549-1676

pii

05-PLME-RA-0092R2

journal_volume

pub_type

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Acute-phase serum amyloid A: an inflammatory adipokine and potential link between obesity and its metabolic complications.