The Role of Triacylglycerol in the Oxidizability of Low Density Lipoproteins and High Density Lipoproteins: Possible Contributions to Atherosclerosis in Metabolic Syndrome

Objective: Metabolic Syndrome (MetS) is a cluster of Cardio-Vascular Disease (CDV) risk factors including visceral obesity, hyperglycemia, hypertension, low HDL cholesterol, hypertriglyceridemia and increased oxidative stress. Pyrene-lipid derivatives selectively incorporated into the hydrophobic core and surrounding amphipathic envelope of LDLs and HDLs are useful markers of the oxidizability of these lipoprotein regions. We performed an observational study aimed at investigating the effect of lipid composition, in particular triacylglycerol (TAG) levels, on the oxidizability of the core and the envelope of LDLs and HDLs in MetS. Methods: We induced changes in the chemical composition of lipoprotein in vivo by placing on a hypocaloric balanced diet fifteen overweight and moderately obese men (BMI: 25-35 kg/mq) with MetS until they lost at least 5% of their initial weight. The core and the surface of LDLs and HDLs were labeled with selective pyrenic probes. Susceptibility to 2,2'-azobis-2-methyl-propanimidamide-dihydrochloride-induced peroxidation was measured following kinetically the decrease of fluorescence of these probes. The length of the lag phase (lag-time) of peroxidation kinetic were calculated and used as indices of lipoprotein oxidizability. In addition, we measured paraoxonase activity and plasma oxidative status. Results: After weight loss, together with a reduction of triglyceridemia and the improvement of the other CDV risk factors associated with MetS, we observed a massive transfer of TAG from HDLs toward LDLs. In the LDLs core, the increased TAG concentration halved the resistance to peroxidation, while in the HDLs core the reduction of this parameter doubled the value of lag-time. In the lipoprotein hydrophobic cores, the duration of lag-time correlated directly with ratio between cholesteryl esters and TAG. No significant changes were found in paraoxonase activity and plasma oxidative status. Conclusions: Less oxidizable HDLs, but also more oxidizable LDLs seem to accompany the improvement of different metabolic factors induced by weight loss in obese men with MetS.