Production of Serum Amyloid a in Response to Inflammatory Cytokines by Human Adipocytes

Serum amyloid A (SAA) is a major acute-phase protein in humans, and elevated plasma levels represent a risk factor for cardiovascular diseases. SAA was thought to be produced by hepatocytes only in response to inflammatory stimuli; moreover, recent studies have shown that adipose tissue can secrete several proinflammatory factors. Therefore, we investigated whether cells in adipose tissue can synthesize SAA in response to inflammatory stimuli. Adipocytes and preadipocytes isolated from abdominal adipose tissue were incubated with IL-1, IL-6, TNF-α, LPS, or resistin at different concentrations. After 48 hours, the supernatants were analyzed by ELISAs for human SAA. Preadipocytes did not show any production in SAA. In contrast, in adipocytes, incubation with TNF-α led to a significant increase in SAA production, peaking after LPS or resistin (∼3 times greater vs unstimulated adipocytes). The greatest increase in SAA occurred with all stimuli combined (∼5 times greater vs control cells). Subsequently, we investigated whether treatment with some drugs could modulate SAA production in adipocytes, and observed that fluvastatin led to a significant inhibition of SAA release, whereas a larger modulation of SAA release was observed after treatment with troglitazone or aspirin. These results show for the first time that human adipocytes, and not preadipocytes, can produce SAA in response to inflammatory cytokines and that this process can be modulated.