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—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-γ (PPARγ), and CCAAT/enhancer binding protein-α (C/EBPα). 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, PPARγ, and C/EBPα 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 &lt;0.001) and insulin (r =0.2125,P &lt;0.002). Leptin and C/EBPα 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 PPARγ mRNA expression. Leptin, PPARγ, and C/EBPα mRNA levels correlated with each other in the intraperitoneal and extraperitoneal fat of obese subjects, but multivariate analysis revealed that only C/EBPα was a predictor of leptin expression in extraperitoneal tissue (partialr =0.6096,P &lt;0.001). Intraperitoneal PPARγ expression was inversely related to fasting insulin (r =−0.2888,P &lt;0.017) and a fasting insulin resistance index (r =−0.2814,P &lt;0.021) in obese subjects. In postobese patients, intraperitoneal PPARγ expression was associated with plasma HDL cholesterol (r =0.5695,P &lt;0.018) and apoA-I (r =0.6216,P &lt;0.008) but was inversely related to LDL cholesterol (r =−0.5101,P &lt;0.03) and apoB (r =−0.6331,P &lt;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-α, and PPAR-γ mRNA expression. Furthermore, our results suggest that C/EBP-α enhances leptin expression in vivo and that PPARγ mRNA expression is inversely associated with cardiovascular risk factors.

arteriosclerosis, thrombosis, and vascular biology

Leptin, Peroxisome Proliferator-Activated Receptor-γ, and CCAAT/Enhancer Binding Protein-α mRNA Expression in Adipose Tissue of Humans and Their Relation to Cardiovascular Risk Factors