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

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. AT dysfunction markers correlated with most lipid-lipoprotein levels. The A/L ratio was negatively associated with fasting insulinemia and HOMA-IR, while SCABD or OME adipocyte size and SCABD CD68 expression were positively related to these variables. Combination of tertiles of largest adipocyte size and lowest A/L ratio showed the highest HOMA-IR. Multiple regression analyses including these markers and TAG levels revealed that the A/L ratio was the only predictor of fasting insulinemia and HOMA-IR. The contribution of the A/L ratio was superseded by adipose cell size in the model where the latter replaced TAGs. Finally, leptinemia was a better predictor of IR than adipocyte size and the A/L ratio in our participants sample.

脂肪组织(Adipose Tissue, AT)功能异常，包括脂肪细胞肥大、巨噬细胞浸润以及分泌型脂肪病（血浆脂联素与瘦素A/L比值降低），均与代谢紊乱密切相关。然而目前尚无研究针对不同年龄与体脂水平的女性群体，对比上述标志物对心血管代谢风险的相对贡献度。本研究对67名女性受试者（年龄40~62岁，体质量指数BMI：17~41 kg/m²）的身体成分、脂肪组织区域分布、脂类-脂蛋白谱、糖稳态以及血浆脂联素与瘦素水平进行了检测。从皮下腹部(subcutaneous abdominal, SCABD)脂肪与网膜(omental, OME)脂肪中，研究者测定了巨噬细胞浸润标志物CD68的表达水平以及脂肪细胞大小。结果显示，脂肪组织功能异常标志物与多数脂类-脂蛋白水平存在显著相关性。A/L比值与空腹胰岛素血症及稳态模型胰岛素抵抗指数(HOMA-IR)呈负相关，而SCABD或OME脂肪的细胞大小以及SCABD组织中CD68的表达水平则与上述指标呈正相关。将脂肪细胞大小处于最高三分位数与A/L比值处于最低三分位数的受试者组合，其HOMA-IR水平最高。纳入上述标志物与三酰甘油(TAG)水平的多元回归分析表明，A/L比值是空腹胰岛素血症与HOMA-IR的唯一预测因子。当以脂肪细胞大小替代三酰甘油纳入模型时，脂肪细胞大小将取代A/L比值的预测贡献度。最终，在本研究的受试者队列中，血浆瘦素水平相较于脂肪细胞大小与A/L比值，是胰岛素抵抗(IR)更优的预测因子。