Influence of obesity on the metabolism of apolipoprotein B in humans.

The influence of obesity on the metabolism of apolipoprotein B (apo B) in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) was investigated in nine obese and seven nonobese Pima Indian men. Kinetics of VLDL-apo B (VLDL-B), VLDL-triglycerides, IDL-B and LDL-B were studied after injection of autologous 131I-VLDL, [3H]glycerol, and autologous 125I-LDL. Specific activities were measured in apo B isolated from all lipoprotein fractions and in triglyceride isolated from VLDL. Transport rates and fractional catabolic rates for apo B in VLDL, IDL, and LDL and triglyceride in VLDL were determined by multicompartmental analysis. This method also allowed the estimation of rates of interconversions of the lipoproteins. The two groups had similar mean ages and heights, but the obese group had a higher total body weight (131 +/- 14 vs. 66 +/- 3 kg +/- SEM) and fat free mass (81 +/- 5 vs. 54 +/- 2 kg) than lean controls. Plasma total lipids were similar for the two groups, and apo B concentrations in VLDL, IDL, and LDL were similar in obese and lean subjects. In spite of similarity in concentrations, obese subjects compared to lean subjects had higher synthetic rates of VLDL-triglyceride (62.6 +/- 15 vs. 26.2 +/- 7 g/d, P less than 0.01), VLDL-B (2,241 +/- 215 vs. 1,113 +/- 72 mg/d, P less than 0.001), and LDL-B (1,234 +/- 87 vs. 802 +/- 83 mg/d, P less than 0.01). Furthermore, in obese subjects, significantly higher amounts of VLDL-B were removed from the circulation without conversion to LDL-B (1,078 +/- 159 vs. 460 +/- 34 mg/d, P less than 0.05), and obese subjects had a higher fractional catabolic rate for LDL than the lean controls (0.48 +/- 0.02 vs. 0.41 +/- 0.02 d-1, P less than 0.05). The rapid catabolism of LDL and increased metabolism of VLDL without conversion to LDL in obese individuals may be mechanisms for maintenance of LDL at normal levels despite the overproduction of its precursor.

[1]  S. Grundy,et al.  Comparisons of metabolism of apolipoprotein B in normal subjects, obese patients, and patients with coronary heart disease. , 1985, The Journal of clinical investigation.

[2]  B V Howard,et al.  Development of an integrated model for analysis of the kinetics of apolipoprotein B in plasma very low density lipoproteins, intermediate density lipoproteins, and low density lipoproteins. , 1985, The Journal of clinical investigation.

[3]  B. Howard,et al.  Plasma and lipoprotein cholesterol and triglyceride concentrations in the Pima Indians: distributions differing from those of Caucasians. , 1983, Circulation.

[4]  S. Grundy,et al.  Isopropanol precipitation method for the determination of apolipoprotein B specific activity and plasma concentrations during metabolic studies of very low density lipoprotein and low density lipoprotein apolipoprotein B. , 1983, Journal of lipid research.

[5]  T. Kita,et al.  Defective lipoprotein receptors and atherosclerosis. Lessons from an animal counterpart of familial hypercholesterolemia. , 1983, The New England journal of medicine.

[6]  S. Grundy,et al.  Increased Low Density Lipoprotein Production Associated with Obesity , 1983, Arteriosclerosis.

[7]  W. A. Bradley,et al.  Receptor-mediated uptake of hypertriglyceridemic very low density lipoproteins by normal human fibroblasts. , 1982, Journal of lipid research.

[8]  W. A. Bradley,et al.  Hypertriglyceridemic very low density lipoproteins induce triglyceride synthesis and accumulation in mouse peritoneal macrophages. , 1982, The Journal of clinical investigation.

[9]  R. Mahley,et al.  Two independent lipoprotein receptors on hepatic membranes of dog, swine, and man. Apo-B,E and apo-E receptors. , 1981, The Journal of clinical investigation.

[10]  A. Kissebah,et al.  Integrated regulation of very low density lipoprotein triglyceride and apolipoprotein-B kinetics in man: normolipemic subjects, familial hypertriglyceridemia and familial combined hyperlipidemia. , 1981, Metabolism: clinical and experimental.

[11]  S. Grundy,et al.  Transport of very low density lipoprotein triglycerides in varying degrees of obesity and hypertriglyceridemia. , 1979, The Journal of clinical investigation.

[12]  M. D'costa,et al.  Low density lipoprotein binding, internalization, and degradation in human adipose cells. , 1979, Canadian journal of biochemistry.

[13]  W. Kannel,et al.  Obesity, lipids, and glucose intolerance. The Framingham Study. , 1979, The American journal of clinical nutrition.

[14]  G. Reaven,et al.  Effect of obesity on the relationship between very low density lipoprotein production rate and plasma triglyceride concentration in normal and hypertriglyceridemic subjects. , 1978, Metabolism: clinical and experimental.

[15]  N. Tolbert,et al.  A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. , 1978, Analytical biochemistry.

[16]  A. Chait,et al.  Regulatory role of insulin in the degradation of low density lipoprotein by cultured human skin fibroblasts. , 1978, Biochimica et biophysica acta.

[17]  B. Lewis,et al.  Conversion of very low density lipoprotein to low density lipoprotein. A metabolic study of apolipoprotein B kinetics in human subjects. , 1975, The Journal of clinical investigation.

[18]  S. Eisenberg,et al.  Very low density lipoprotein "remnant" particles: uptake by aortic smooth muscle cells in culture. , 1973, Biochimica et biophysica acta.

[19]  G Bucolo,et al.  Quantitative determination of serum triglycerides by the use of enzymes. , 1973, Clinical chemistry.

[20]  P. Barter,et al.  Plasma free fatty acid transport during prolonged glucose consumption and its relationship to plasma triglyceride fatty acids in man. , 1972, Journal of lipid research.

[21]  D. Bilheimer,et al.  The metabolism of very low density lipoprotein proteins. I. Preliminary in vitro and in vivo observations. , 1972, Biochimica et biophysica acta.

[22]  T. Miettinen,et al.  Cholesterol Production in Obesity , 1971, Circulation.

[23]  P. Nestel,et al.  Plasma free fatty acid and triglyceride turnover in obesity. , 1968, Metabolism: clinical and experimental.

[24]  A. Mcfarlane,et al.  Efficient Trace-labelling of Proteins with Iodine , 1958, Nature.

[25]  J. Folch,et al.  A simple method for the isolation and purification of total lipides from animal tissues. , 1957, The Journal of biological chemistry.

[26]  G. Reaven,et al.  Effects of weight reduction on obesity. Studies of lipid and carbohydrate metabolism in normal and hyperlipoproteinemic subjects. , 1974, The Journal of clinical investigation.

[27]  Josef Brozek,et al.  Techniques for measuring body composition , 1961 .