Triglycéridémie postprandiale, insulinémie, leptinémie et distribution des apolipoprotéines CIII entre TGRL et HDL chez l’homme normolipidémique

Hypertriglyceridemia, insulinemia, leptinemia and distribution of apoCIII between TGRL-CIII and HDL in normolipidemic subjects

Laboratoire de biochimie pharmaceutique, 2, avenue du Pr-L.-Bernard, Université de Rennes I, 35000 Rennes, France

Résumé

Notre article, publié en 1998 dans OCL sur la « Leptine, épuration et utilisation postprandiales des lipides chez l’homme », faisait état pour la première fois d’un lien entre cette hormone produite par le tissu adipeux et le risque de maladies cardiovasculaires lié à un défaut d’épuration des lipides en période postprandiale.

Abstract

Fasting hypertriglyceridemia is now recognized as an independent risk factor for atheromatosis. The postprandial delay clearance of triglyceride-rich lipoproteins (TGRL and remnants) per se is also responsible for an increased risk of atheroma and cardiovascular disease, despite normal fasting levels of triglycerides. Triglyceridemia is a member of the pluri-metabolic syndrome parameters often associated with diabetes or obesity and conduces to an increased risk of cardiovascular disease. These pathologies are generally associated with increased levels of insulin and leptin. Leptin is synthesised by the adipocyte tissue and represents a physiological satiety factor. Leptin plasma levels are a function of the degree of the subject’s adiposity. The TG intravascular metabolism is modulated by apolipoprotein CIII (ApoCIII), and is linked to the ApoCIII levels associated with TGRL (TGRL-CIII), which increase postprandially or during pathological hypertriglyceridemia. The role of ApoCIII is to delay the clearance of TG and TGRL by limiting their intravascular lipolysis and receptor-mediated cellular clearance. Distribution of ApoCIII between TGRL-CIII and HDL (HDL-CIII) is critical for TG metabolism: increased fasting TGRL-CIII levels have been shown to be correlated to atherosclerotic progression in subjects with coronary artery disease (CAD), and to a delayed postprandial TG response in normolipidemic CAD subjects. We thus investigated in a group of normolipidemic non obese males, the individual potential links of these parameters (TG, ApoCIII, insulin, leptin) with the postprandial response to a 1,000 kcal, 62.5% fat, test meal. 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 strong positive correlation of leptin levels with BMI (p<0.001), with fasting insulin (p<0.001), with fasting TG (p<0.02) and fasting TGRL-CIII (p<0.01). As expected and previously shown, fasting TGRL-CIII correlated positively with fasting TG (p<0.001). Postprandially, TG and TGRL-CIII levels increased significantly and concomitantly, at 2 and 4 hours, while HDL-CIII showed a mirror-like decrease. Furthermore, delayed postprandial clearance evidenced by higher levels of late postprandial TG and TGRL-CIII (6 or 8 hours after the test meal) were positively correlated with the fasting insulin (p<0.05), leptin and TGRL-CIII levels (p<0.001). Thus, the putative pro-atherogenic delayed postprandial response expressed by higher TG and TGRL-CIII values persisting 6 or 8 hours after the test meal, is positively correlated with higher fasting insulin (p<0.05) and leptin levels (p<0.001), and higher fasting TGRL-CIII (p<0.001) in normolipidemic non obese males.