To investigate the regulation of serum levels of cholesterol precursor sterols and plant sterols, these noncholesterol sterols, fatty acids, and various parameters of cholesterol metabolism were analyzed in 63 volunteers from a randomly selected Finnish male population sample of 100 subjects, aged 50 years, who had normal dietary habits. Serum levels of cholesterol precursors, desmosterol and lathosterol (in terms of micrograms/mg cholesterol), were negatively related to both the fractional and absolute absorption of dietary cholesterol and serum high density lipoprotein (HDL) cholesterol, and positively related to overall cholesterol synthesis and serum very low density lipoprotein (VLDL) cholesterol. Serum levels of the plant sterols, campesterol and sitosterol, exhibited positive correlations with the polyunsaturated/saturated fatty acid ratio of dietary fat, the linoleic acid contents of plasma and dietary lipids, the amount of dietary plant sterols (as indicated by fecal output), fractional and absolute absorption of dietary cholesterol, and HDL cholesterol, but were inversely related to the overall cholesterol synthesis and VLDL cholesterol. Stepwise multiple regression analysis revealed that the serum level of campesterol was associated with fractional cholesterol absorption, dietary plant sterols, and biliary cholesterol secretion, and that of sitosterol with dietary plant sterols, cholesterol synthesis, fractional cholesterol absorption, and biliary cholesterol secretion. Thus, the serum non-cholesterol sterols are significant indicators of cholesterol absorption and synthesis even under basal conditions and, since gas liquid chromatographic determination of these sterols is quite simple, their measurement may be valuable for monitoring cholesterol metabolism in large-scale epidemiologic studies.
Efficiency of cholesterol absorption in the variation of plasma cholesterol level was studied in a random sample of middle-aged Finnish men. Compared with the subjects in the highest decile of plasma cholesterol, those in the lowest decile had a lower cholesterol absorption and, as measured with the serum contents of the cholesterol precursor sterols lanosterol and lathosterol, a higher cholesterol synthesis, the values for the subjects in the middle decile falling in between. Also, the serum content of betasitosterol, a plant sterol used as an additional indicator of cholesterol absorption, was high in the highest decile and low in the lowest decile of the plasma low density lipoprotein (LDL) cholesterol level. Among the whole study group the fractional absorption of cholesterol was positively correlated with the plasma cholesterol level, and a negative correlation was observed between the amount of absorbed dietary cholesterol and the cholesterol synthesis. Thus, the efficiency of cholesterol absorption has an important role in the determination of the plasma cholesterol level among the Finnish male population.
A B S T R A C T Low density lipoprotein (LDL) catabolism occurs by LDL receptor-dependent and LDL receptor-independent pathways. We have shown previously that nonenzymatic glucosylation of LDL in the presence of cyanoborohydride irreversibly blocks the lysine residues of LDL. Glucosylated LDL (GLC-LDL) was not degraded by the LDL receptor of fibroblasts, and its degradation by macrophages was similar to that of native LDL. This suggested that GLC-LDL should be a good tracer of LDL receptorindependent catabolism, and if combined with a tracer of total LDL catabolism, should enable one to calculate the extent of LDL receptor-dependent catabolism.To determine the contribution of each pathway in man, we prepared '25I-GLC-LDL and '"'I-control LDL and simultaneously determined the fractional catabolic rate (FCR) of each tracer in four subjects. In preliminary experiments, we showed that the conditions for glucosylation did not affect LDL turnover. In the four subjects, the FCR for total LDL catabolism ranged from 0.345 to 0.724 d-' with a mean of 0.57±0.16 d-'. The FCR of GLC-LDL varied from 0.071 to 0.141 d-' with a mean of 0.11±0.03 d-'. The latter is similar to the FCR reported for native LDL in subjects with homozygous familial hypercholesterolemia, supporting the interpretation that GLC-LDL traces only the receptor-independent pathway. De-spite the wide range of total LDL catabolism in these subjects, LDL receptor-independent catabolism ac-
A lineshape fitting model was constructed for classifying the overlapping information in the 1H NMR spectrum of human blood plasma. A reliable assignment of the overlapping fatty acid (-CH2-)n and -CH3 resonances of the various lipoproteins (VLDL, very low density lipoprotein; LDL, low density lipoprotein; HDL high density lipoprotein) is introduced, and for the first time detailed characteristics (chemical shifts, half linewidths, and relative intensities) of the individual lipoprotein components were obtained directly from the whole plasma spectrum. This was achieved by combining the constructed lineshape fitting model and the proper 400 MHz proton NMR measurements from blood plasma of a healthy donor, from fractions of the different lipoproteins, and from plasma samples in which the lipoprotein fractions were separately added. The results suggest fair promise of future applications of the rapid and easy NMR analysis of lipoprotein distribution in various research and clinical situations.
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