Adipose tissue as an endocrine organ: production of serum amyloid a in response to inflammatory cytokines by human adipocytes

Abstract

Background: Serum amyloid A (SAA) is one of the major acute-phase proteins in humans, and elevated plasma levels of this protein represent a risk factor for the development of cardiovascular disease. At first SAA was thought to be produced by hepatocytes in response to inflammatory stimuli, but several studies have shown that adipose tissue can secrete a number of biologically active molecules, including several proinflammatory factors. Therefore, we tested the hypothesis that cells in adipose tissue can synthesize SAA in response to inflammatory stimuli. Methods and results: Adipocytes and preadipocytes were isolated from abdominal adipose tissue and incubated with interleukin-1 and -6, tumor necrosis factor-α (TNF-α), lipopolysaccharide (LPS), or resistin, or a combination of these proteins, at different concentrations. After 48 hours, the supernatants were analyzed by using ELISAs specific for human SAA. Incubation with TNF-α led to a significant increase in SAA production, with a peak after incubation with either LPS or resistin (∼3 times greater than that in control adipocytes). In addition, the biggest increase in SAA occurred in cells exposed to all stimuli combined (∼5 times greater than that in control cells). Subsequently we investigated whether treatment with some drugs could modulate SAA production, and we observed that treatment with fluvastatin led to a significant, but not complete, inhibition of SAA release from adipocytes, whereas a large, but still not complete, modulation of SAA release from adipocytes was observed after treatment with either troglitazone or aspirin. ![Figure][1] Conclusions: These results show for the first time that human adipocytes can produce SAA in response to inflammatory cytokines, thereby suggesting a new link between obesity and vascular inflammation. [1]: pending:yes