The anti-atherogenic aspect of metformin treatment in insulin resistant women with the polycystic ovary Syndrome: Role of the newly established pro-inflammatory adipokine Acute-phase Serum Amyloid A; evidence of an adipose tissue-monocyte axis

Objective: Acute-phase Serum Amyloid A (ASAA) is a novel pro-inflammatory adipokine, increased in obese, insulin resistant subjects. Polycystic ovary syndrome (PCOS) is associated with inflammation and atherosclerosis. We assessed sera, adipose tissue (AT) mRNA and protein levels of ASAA of PCOS women and matched controls. Ex vivo regulation of AT ASAA by d-glucose, effects of metformin treatment on circulating ASAA in PCOS subjects and effects of sera from normal and PCOS subjects (before and after metformin) on ASAA production (THP-1 macrophages) were also studied. Methods and results: Circulating ASAA (ELISA), subcutaneous and omental AT ASAA mRNA (RT-PCR) and protein (western blotting) were significantly higher in PCOS women (P< 0.05). In AT explants, glucose significantly increased ASAA production and secretion (P< 0.05, P< 0.01). Furthermore, ASAA production (THP-1 macrophages) was significantly greater by sera from PCOS women compared to controls (P< 0.01). ASAA protein production was significantly decreased by sera from PCOS women following 6 months of metformin treatment (P< 0.05). After 6 months of metformin treatment, there was a significant decrease in circulating ASAA (P< 0.05). Importantly, changes in intima media thickness were predictive of changes in circulating ASAA (P= 0.034). Conclusion: Serum and AT ASAA are increased in PCOS women and are elevated by glucose. Metformin treatment decreases serum ASAA in these women. An adipose tissue-monocyte axis may be pivotal in the pathogenesis of inflammation and atherosclerosis. ASAA may be a valuable diagnostic marker in the management of dysmetabolic states including PCOS.