Human obesity: from lipid abnormalities to lipid oxidation
Van Gaal, L.F.; Zhang, A.; Steijaert, M.M.; De Leeuw, I.H.
International Journal of Obesity and Related Metabolic Disorders Journal of the International Association for the Study of Obesity 19(Suppl): S21-S26
1995
ISSN/ISBN: 0307-0565 PMID: 8581073 Document Number: 444749
The obese state has been recognized to accentuate the known risk factors 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 hypercholesterolemia, high fasting (and postprandial) triglyceride levels, low HDL cholesterol, high apolipoprotein B, high small dense lipoprotein particles and alterations of serum and tissue LPL-activity. Although obesity is associated with such cluster of lipid abnormalities, these factors do not explain the complete process of atherogenesis in the obese 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 last decade, a series of excellent studies have provided the background for a more indepth mechanism of atherosclerosis; the role of lipid peroxidation in particular has been one of the focuses of this current research. There exists a lot of evidence suggesting a major role for oxidized 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 them to 18 age-matched controls. The oxidizability of the non-HDL fraction is evaluated by measuring the fluorescence and thiobarbituric acid reactive substances (TBARS: MDA nM/mg non-HDL) at different time intervals of incubation. TBARS formation increased linearly with the increase of lipids both in non-obese and obese subjects. TBARS, measured every 300', increased in non-obese controls up to a max. of 59.6 at 180' in contrast to a max. of 77.1 at 180' (p lt 0.001) in obese subjects. Also the lag-time (period from zero to the start of the particle oxidation process) was significantly lower (92.5 vs 123.4; p lt 0.001) of obese subjects, when compared to lean controls. BMI correlates significantly with TBARS formation and its log transformed values (max p lt 0.001). The lag-time was negatively related to body weight and BMI and the waist-to-hip ratio. A significant relationship exists between TBARS formation (up to r = 0.59) and triglyceride levels and a negative relationship exists with HDL-cholesterol levels. In vitro oxidizability of non-HDL lipoproteins is significantly increased in obese, non diabetic subjects and related to increased body weight and triglyceride levels. Further studies are necessary to explore the underlying mechanisms for this phenomenon and the effects of weight reduction and anti-oxidants ingestion.