Effect of obesity on growth-related oncogene factor-alpha, thrombopoietin, and tissue inhibitor metalloproteinase-1 serum levels.

We have recently identified several adipokines as oversecreted by omental adipose tissue (AT) of obese subjects: two chemokines (growth-related oncogene factor-alpha (GRO-alpha), macrophage inflammatory protein-1 beta (MIP-1 beta)), a tissue inhibitor of metalloproteinases-1 (TIMP-1), an interleukin-7 (IL-7) and a megakaryocytic growth-factor (thrombopoietin (TPO)). These adipokines are involved in insulin resistance and atherosclerosis. The objectives of this study were to determine whether the circulating levels of these adipokines were increased in obesity and to identify the responsible factors. A cross-sectional study including 32 lean (BMI (kg/m(2)) <25), 15 overweight (BMI: 25-29.9), 11 obese (BMI: 30-39.9), and 17 severely obese (BMI >40) age-matched women was carried out. Serum adipokine levels, insulin sensitivity, and substrate oxidation were measured by ELISA, euglycemic-hyperinsulinemic clamp, and indirect calorimetry, respectively. Circulating levels of GRO-alpha, TPO, and TIMP-1 were higher in obese and/or severely obese women than in lean ones (+30, 55, and 20%, respectively). Serum levels of these adipokines positively correlated with insulinemia or glycemia, and negatively with insulin sensitivity. TIMP-1 also positively correlated with blood pressure, and TPO with triglyceride levels. Multiple regression analysis showed that fat mass per se was an independent determinant of GRO-alpha, TPO, and TIMP-1 levels, suggesting that hypertrophied adipocytes and recruited macrophages in expanded AT mainly contribute to this hyperadipokinemia. Insulinemia, glycemia and resistance of glucose oxidation to insulin were additional predictors for TPO. Circulating GRO-alpha, TPO, and TIMP-1 levels are increased in obesity. This may be partially due to augmented adiposity per se and to hyperinsulinemia/insulin resistance. These high systemic levels may in turn worsen/promote insulin resistance and cardiovascular disease.