Contribution of markers of adiposopathy and adipose cell size in predicting insulin resistance markers in women of varying age and adiposity

Markers of adipose tissue (AT) dysfunctions, such as adipocyte hypertrophy, macrophage infiltration and secretory adiposopathy (low plasma adiponectin/leptin, A/L, ratio), associate with metabolic disorders. However, no study has compared the relative contribution of these markers to cardiometabolic risk in women of varying age and adiposity. Body composition, regional AT distribution, lipid-lipoprotein profile, glucose homeostasis and plasma A and L levels were determined in 67 women (age: 40-62 years; BMI: 17-41 kg/m2). Expression of macrophage infiltration marker CD68 and adipocyte size were measured from subcutaneous abdominal (SCABD) and omental (OME) fat samples. AT dysfunction markers were correlated with most lipid-lipoprotein levels such as TAGs (-0.36<rho<0.46; 0.0005<p<0.05), except OME CD68 expression which was negatively related to HDL-cholesterol. The A/L ratio was negatively associated with fasting insulinemia and HOMA-IR (-0.60<rho<-0.63; p<0.0001), while SCABD or OME adipocyte size and SCABD CD68 expression were positively related to these variables (0.39<rho<0.59; p<0.01). Multiple regression analyses including these markers and triacylglycerol (TAG) levels revealed that the A/L ratio was the only predictor of fasting insulinemia and HOMA-IR (partial R2=0.31-0.33; 0.000<p<0.005) in the model with TAGs and CD68 expression. However, the contribution of the A/L ratio was supplanted by adipose cell size in the model where the latter replaced TAGs. Combination of tertiles of largest adipocyte size and lowest A/L ratio showed the highest HOMA-IR. Taken together, our results show that adipocyte hypertrophy combined with reduced A/L ratio was related to increased IR, suggesting an independent contribution of both markers to the variance of cardiometabolic risk.