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Introduction
Polycystic ovary syndrome (PCOS) is estimated to affect 5–7% of premenopausal females and is associated with a significant risk of developing type two diabetes (T2D), independently of obesity (1). PCOS is characterized by a hyperandrogenic state, and exposure to exogenous testosterone in vivo has been associated with low-grade chronic inflammation in rats and human females. Low-grade chronic inflammation has an important function in the development of insulin resistance, as it triggers the metabolic syndrome (2,3). The risk of developing the metabolic syndrome in adolescent females with PCOS is correlated with increasing concentrations of bioavailable testosterone, an effect which is independent of obesity (4). However, the mechanism by which hyperandrogenism results in the development of low-grade chronic inflammation remains undefined.
Studies have shown that in patients with PCOS, a number of proinflammatory factors, such as interleukin-6 (IL-6), macrophage chemotactic protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α), are positively correlated with serum testosterone concentration. An association between low-grade chronic inflammation and testosterone levels has been demonstrated by intervention studies using simvas-tatin (5) and flutamide (6) in PCOS. When mononuclear cells from the peripheral blood of PCOS patients were exposed to high-sugar conditions in vitro, the concentration of TNF-α in the supernatant was positively correlated with the serum testosterone level. We hypothesised that excess androgen in PCOS may be a key factor in the development of low-grade chronic inflammation (7).
Adipocytes have a crucial function in low-grade chronic inflammation as these cells are sources of cytokines (IL-6, and MCP-1) that are secreted during the activation of certain signalling cascades, which are involved in insulin resistance (8). Current research also suggests that low-grade chronic inflammation is initiated and controlled by adipose tissue as weight loss is able to significantly alleviate low-grade chronic inflammation (9,10). Adipocytes are an important component of adipose tissue and are classic insulin target cells. These cells have a function in the storage and maintenance of energy, and in the balance of glucose and lipid metabolism. In addition, fat cells, in a similar manner to immune cells, activate complement components, such as C3 and produce proinflammatory mediators and chemokines, such as IL-6 and MCP-1, thus triggering inflammation signaling pathways, including p38 mitogen-activated protein kinase (p38-MAPK), extracellular signal-regulated kinase (ERK), inhibitor of nuclear factor-κB (IKK-β/NF-κB)...