LEPTIN, POSTPRANDIAL UTILIZATION OF LIPIDS IN HUMANS

Obesity and dyslipidemia are often associated and conduce to an increa sed risk of cardio-vascular disease. Enterostatin and leptin represent physiological satiety factors, and their plasmatic levels are modifie d in obese subjects. Enterostatin, at the entrance of the metabolic pa thway, is representative of a satiety signal from the intestine, speci fically directed towards lipids, and leptin at the end of this pathway , represents another regulation produced by the adipose tissue, respon sible for the << fuel >> homeostasis and storage. Triglycerides (TG) r epresent a pathway for energy transportation. Fasting hypertriglycerid emia is now recognized as an independent risk factor for atheromatosis , and the postprandial delay clearance of triglyceride rich lipoprotei ns (TGRL and remnants), per se, is also responsible of an increased ri sk of atheroma and cardio-vascular disease, despite normal fasting lev els of triglycerides. The intra-vascular metabolism of triglycerides i s modulated by apolipoprotein CIII (Apo-CIII), and is linked to the le vels of Apo-CIII associated to TGRL (TGRL-CIII), which increase postpr andially or during pathological hypertriglyceridemia. The role of Apo- CIII is to delay the clearance of TG and TGRL, by limiting intra-vascu lar lipolysis and receptor cellular clearance. Distribution of Apo-CII I between Triglyceride-Rich-Lipoprotein (TGRL-CIII) and HDL (HDL-CIII) is critical for TC metabolism : increased fasting CIII-ratio (TGRL-CI II/HDL-CIII) levels have been shown to be correlated to atheroscleroti c progression in subjects with coronary artery disease (CAD), and to a delayed postprandial triglyceride response in normolipidemic CAD subj ects. Thus we investigated, in 35 normolipidemic non obese males, the individual potential links of these parameters with the postprandial r esponse to a 1 000 Kcal, 60% fat, test meal given at 7 am. In fasting state, these normolipidemic non obese males, within a low range of BMI (21 +/- 2) and rather low fasting levels of leptin, still showed a st rong positive correlation of leptin levels with BMI (p<0.001), with in sulin (p<0.001), with fasting triglycerides (p<0.02) and fasting TGRL- CIII or CIII-ratio (p<0.01). As expected and previously shown, fasting TGRL-CIII or CIII-ratio correlated positively with fasting triglyceri des (p<0.001). Postprandially, TC and TGRL-CIII levels increased signi ficantly and concomitantly, at 2 and 4 hours, while HDL-CIII showed a mirror-iike decrease, inducing higher postprandial CIII-ratio. The cir cadian leptin cycle induced a mean decrease of 10% (NS) through the te st meal study. Furthermore, the late post prandial values of triglycer ides and TGRL-CIII, 6 or 8 hours after the test meal were positively c orrelated with the early fasting leptin and CIII-ratio levels (p<0.001 ). Thus the putative pro-atherogenic delayed postprandial response exp ressed by higher triglycerides and TGRL-CIII values persisting 6 or 8 hours after a test meal, is positively correlated with higher lasting leptin level (p<0.001), and higher lasting CIII-ratio (p<0.001) in nor molipidemic non obese males. This work was supported by grants from ON I-DOL and CETIOM.