Leptin, peroxisome proliferator-activated receptor-gamma, and CCAAT/enhancer binding protein-alpha mRNA expression in adipose tissue of humans and their relation to cardiovascular risk factors

Obesity is a prevalent disorder that increases the risk for premature cardi ovascular disease. The adipose tissue itself plays an active role in the re gulation of fuel metabolism and energy homeostasis by expressing a number o f regulatory genes, such as leptin, peroxisome proliferator-activated recep tor-gamma (PPAR gamma), and CCAAT/enhancer binding protein-alpha (C/EBP alp ha). To study the in vivo relationships among these genes and their associa tions with cardiovascular risk factors, plasma levels of leptin, lipids, ap olipoproteins (apo), insulin, and glucose were measured in 216 obese, 165 n onobese, and 36 weight-losing postobese subjects. mRNA expression of leptin , PPAR gamma, and C/EBP alpha in the extraperitoneal and intraperitoneal ad ipose tissue was quantified in subsets of subjects. In obese individuals, p lasma leptin was associated with apoA-I (r=0.2346, P<0.001) and insulin (r= 0.2125, P<0.002). Leptin and C/EBP alpha mRNA expression in extraperitoneal and intraperitoneal adipose tissue of obese patients was higher than in th e respective tissues of nonobese or postobese subjects. No significant diff erences among the study groups were found for PPAR gamma mRNA expression. L eptin, PPAR gamma, and C/EBP alpha mRNA levels correlated with each other i n the intraperitoneal and extraperitoneal fat of obese subjects, but multiv ariate analysis revealed that only C/EBP alpha was a predictor of leptin ex pression in extraperitoneal tissue (partial r=0.6096, P<0.001). Intraperito neal PPAR gamma expression was inversely related to fasting insulin (r=-0.2 888, P<0.017) and a fasting insulin resistance index (r=-0.2814, P<0.021) i n obese subjects. In postobese patients, intraperitoneal PPAR gamma express ion 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=-0.5 101, P<0.03) and apoB (r=-0.6331, P<0.007). These findings suggest a relati onship between plasma leptin and HDL metabolism as well as adipose-tissue s ite-dependent associations among leptin, C/EBP-alpha, and PPAR-gamma mRNA e xpression. Furthermore, our results suggest that C/EBP-alpha enhances lepti n expression in vivo and that PPAR gamma mRNA expression is inversely assoc iated with cardiovascular risk factors.