HUMAN OBESITY - FROM LIPID ABNORMALITIES TO LIPID OXIDATION

The obese state has been recognizedz to accentuate the known risk fact ors for atherosclerotic disease as dyslipidemia, hypertension, glucose intolerance and insulin resistance. Among other risk factors, obesity is characterized by a series of lipid disturbances, such as hyperchol esterolemia, high fasting (and postprandial) triglyceride levels. low HDL cholesterol, high apolipoprotein B, high small dense lipoprotein p articles and alterations of serum and tissue LPL-activity. Although ob esity is associated with such cluster of lipid abnormalities, these fa ctors do not explain the complete process of atherogenesis in the obes e subject. Other risk factors belonging to the polymetabolic syndrome- cluster, insulin resistance, hypertension, fibrinogen. add substantial but not full explanation to the atherothrombotic process. Over the la st decade. a series of excellent studies have provided the background for a more in depth mechanism of atherosclerosis; the role of lipid pe roxidation in particular has been one of the focuses of this current r esearch. There exists a lot of evidence suggesting a major role for ox idized LDL and VLDL particles in the pathogenesis of atherosclerosis. Although obesity is characterized by dyslipidemia. less is known about the oxidation capacity of lipoproteins in obese subjects. We measured the oxidizability in vitro in 21 premenopausal women and compared the m to 18 age-matched controls. The oxidizability of the non-HDL fractio n is evaluated by measuring the fluorescence and thiobarbituric acid r eactive substances (TBARS: MDA nM/mg non-HDL) at different time interv als of incubation. TBARS formation increased linearly with the increas e of lipids both in non-obese and obese subjects. TEARS. measured ever y 300', increased in non-obese controls up to a max. of 59.6 at 180' i n contrast to a max. of 77.1 at 180' (p < 0,001) in obese subjects. Al so the lag-time (period from zero to the start of the particle oxidati on process) was significantly lower (92.5 vs 123.4;p < 0.001) of obese subjects, when compared to lean controls. BMI correlates significantl y with TEARS formation and its log transformed values (max p < 0.001). The lag-time was negatively related to body weight and BMI and the wa ist-to-hip ratio. A significant relationship exists between TBARS form ation (up to r = 0.59) and triglyceride levels and a negative relation ship exists with HDL-cholesterol levels. In vitro oxidizability of non -HDL lipoproteins is significantly increased in obese, non diabetic su bjects and related to increased body weight and triglyceride levels. F urther studies are necessary to explore the underlying mechanisms for this phenomenon and the effects of weight reduction and anti-oxidants ingestion.