Krempler F, Breban D, Oberkofler H, Esterbauer H, Hell E, Paulweber B, Patsch W
Department of Internal Medicine, Krankenhaus Hallein, Austria.
Arterioscler Thromb Vasc Biol. 2000 Feb;20(2):443-9. doi: 10.1161/01.atv.20.2.443.
Obesity is a prevalent disorder that increases the risk for premature cardiovascular disease. The adipose tissue itself plays an active role in the regulation of fuel metabolism and energy homeostasis by expressing a number of regulatory genes, such as leptin, peroxisome proliferator-activated receptor-gamma (PPARgamma), and CCAAT/enhancer binding protein-alpha (C/EBPalpha). To study the in vivo relationships among these genes and their associations with cardiovascular risk factors, plasma levels of leptin, lipids, apolipoproteins (apo), insulin, and glucose were measured in 216 obese, 165 nonobese, and 36 weight-losing postobese subjects. mRNA expression of leptin, PPARgamma, and C/EBPalpha in the extraperitoneal and intraperitoneal adipose tissue was quantified in subsets of subjects. In obese individuals, plasma leptin was associated with apoA-I (r=0.2346, P<0.001) and insulin (r=0.2125, P<0.002). Leptin and C/EBPalpha mRNA expression in extraperitoneal and intraperitoneal adipose tissue of obese patients was higher than in the respective tissues of nonobese or postobese subjects. No significant differences among the study groups were found for PPARgamma mRNA expression. Leptin, PPARgamma, and C/EBPalpha mRNA levels correlated with each other in the intraperitoneal and extraperitoneal fat of obese subjects, but multivariate analysis revealed that only C/EBPalpha was a predictor of leptin expression in extraperitoneal tissue (partial r=0.6096, P<0.001). Intraperitoneal PPARgamma expression was inversely related to fasting insulin (r=-0.2888, P<0.017) and a fasting insulin resistance index (r=-0.2814, P<0.021) in obese subjects. In postobese patients, intraperitoneal PPARgamma expression was associated with plasma HDL cholesterol (r=0.5695, P<0.018) and apoA-I (r=0.6216, P<0.008) but was inversely related to LDL cholesterol (r=-0.5101, P<0.03) and apoB (r=-0.6331, P<0.007). These findings suggest a relationship between plasma leptin and HDL metabolism as well as adipose-tissue site-dependent associations among leptin, C/EBP-alpha, and PPAR-gamma mRNA expression. Furthermore, our results suggest that C/EBP-alpha enhances leptin expression in vivo and that PPARgamma mRNA expression is inversely associated with cardiovascular risk factors.
肥胖是一种常见疾病，会增加过早发生心血管疾病的风险。脂肪组织本身通过表达多种调节基因，如瘦素、过氧化物酶体增殖物激活受体γ（PPARγ）和CCAAT/增强子结合蛋白α（C/EBPα），在调节燃料代谢和能量平衡中发挥积极作用。为了研究这些基因之间的体内关系及其与心血管危险因素的关联，我们测量了216名肥胖者、165名非肥胖者和36名减肥后的肥胖者的血浆瘦素、脂质、载脂蛋白（apo）、胰岛素和葡萄糖水平。在部分受试者中对腹膜外和腹膜内脂肪组织中瘦素、PPARγ和C/EBPα的mRNA表达进行了定量分析。在肥胖个体中，血浆瘦素与apoA-I（r = 0.2346，P < 0.001）和胰岛素（r = 0.2125，P < 0.002）相关。肥胖患者腹膜外和腹膜内脂肪组织中瘦素和C/EBPα的mRNA表达高于非肥胖或减肥后肥胖受试者的相应组织。各研究组之间PPARγ mRNA表达未发现显著差异。肥胖受试者腹膜内和腹膜外脂肪中瘦素、PPARγ和C/EBPα的mRNA水平相互关联，但多变量分析显示，只有C/EBPα是腹膜外组织中瘦素表达的预测因子（偏相关系数r = 0.6096，P < 0.001）。肥胖受试者腹膜内PPARγ表达与空腹胰岛素（r = -0.2888，P < 0.017）和空腹胰岛素抵抗指数（r = -0.2814，P < 0.021）呈负相关。在减肥后肥胖患者中，腹膜内PPARγ表达与血浆高密度脂蛋白胆固醇（r = 0.5695，P < 0.018）和apoA-I（r = 0.6216，P < 0.008）相关，但与低密度脂蛋白胆固醇（r = -0.5101，P < 0.03）和apoB（r = -0.6331，P < 0.007）呈负相关。这些发现提示血浆瘦素与高密度脂蛋白代谢之间存在关联，以及瘦素、C/EBP-α和PPAR-γ mRNA表达之间存在脂肪组织部位依赖性关联。此外，我们的结果提示C/EBP-α在体内增强瘦素表达，且PPARγ mRNA表达与心血管危险因素呈负相关。
