DIURNAL HETEROGENEITY IN STRUCTURE AND FUNCTION OF LOW-DENSITY LIPOPROTEINS OF NORMOLIPIDEMIC MALES

Structural changes in low density lipoproteins (LDL) have been shown t o alter their metabolism and atherogenic potential. We investigated th e diurnal changes in size and composition of LDL in seven healthy, non -obese, normolipidemic male volunteers consuming a standard diet (14.5 % protein, 31.9% fat, 53.6% carbohydrate and 383 mg cholesterol/day) a nd continuing their daily routine. The food was divided into three mea ls and three snacks, and blood samples were abtained al 7 AM (after 12 h fasting), noon, 8 PM, midnight and 3 AM. LDL were isolated by both sequential and density gradient ultracentrifugation (d = 1.019-1.050 g /ml), and analyzed for lipids, apolipoproteins, size, and affinity to LDL receptors. Diurnal LDL preparations differ from fasting LDL in bot h chemical and physical parameters. The former get richer in triglycer ide (TG/cholesterol weight ratio 0.23 vs. 0.16), larger in diameter (2 1.2+/-0.2 vs. 22.4+/-0.1 nm), and enriched in a more buoyant fraction (74.0+/-4.6 vs. 41.9+/-3.8% of LDL cholesterol in d = 1.019-1.035 g/ml ). These structural changes in LDL were associated with enhanced affin ity to LDL receptors in both human skin fibroblasts and HepG2 cells, a s demonstrated by competition experiments with fasting human I-125-LDL . The observed diurnal heterogeneity in both the structure and the fun ction of LDL may be attributed to the absorptive state as it did nor o ccur during prolonged fasting. These diurnal changes may be important for better understanding LDL metabolism in vivo and for the elucidatio n of the atherogenic process.