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. 1985 Aug;76(2):596–603. doi: 10.1172/JCI112011

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

G Egusa, W F Beltz, S M Grundy, B V Howard
PMCID: PMC423865  PMID: 4031064

Abstract

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.

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Selected References

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  1. Angel A., D'Costa M. A., Yuen R. Low density lipoprotein binding, internalization, and degradation in human adipose cells. Can J Biochem. 1979 Jun;57(6):578–587. doi: 10.1139/o79-073. [DOI] [PubMed] [Google Scholar]
  2. Barter P. J., Nestel P. J. Plasma free fatty acid transport during prolonged glucose consumption and its relationship to plasma triglyceride fatty acids in man. J Lipid Res. 1972 Jul;13(4):483–490. [PubMed] [Google Scholar]
  3. Beltz W. F., Kesäniemi Y. A., Howard B. V., Grundy S. M. 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. J Clin Invest. 1985 Aug;76(2):575–585. doi: 10.1172/JCI112009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bierman E. L., Eisenberg S., Stein O., Stein Y. Very low density lipoprotein "remnant" particles: uptake by aortic smooth muscle cells in culture. Biochim Biophys Acta. 1973 Nov 2;329(1):163–169. doi: 10.1016/0304-4165(73)90021-4. [DOI] [PubMed] [Google Scholar]
  5. Bilheimer D. W., Eisenberg S., Levy R. I. The metabolism of very low density lipoprotein proteins. I. Preliminary in vitro and in vivo observations. Biochim Biophys Acta. 1972 Feb 21;260(2):212–221. doi: 10.1016/0005-2760(72)90034-3. [DOI] [PubMed] [Google Scholar]
  6. Bucolo G., David H. Quantitative determination of serum triglycerides by the use of enzymes. Clin Chem. 1973 May;19(5):476–482. [PubMed] [Google Scholar]
  7. Chait A., Bierman E. L., Albers J. J. Regulatory role of insulin in the degradation of low density lipoprotein by cultured human skin fibroblasts. Biochim Biophys Acta. 1978 May 25;529(2):292–299. doi: 10.1016/0005-2760(78)90072-3. [DOI] [PubMed] [Google Scholar]
  8. Egusa G., Brady D. W., Grundy S. M., Howard B. V. 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. J Lipid Res. 1983 Sep;24(9):1261–1267. [PubMed] [Google Scholar]
  9. FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
  10. Gianturco S. H., Bradley W. A., Gotto A. M., Jr, Morrisett J. D., Peavy D. L. Hypertriglyceridemic very low density lipoproteins induce triglyceride synthesis and accumulation in mouse peritoneal macrophages. J Clin Invest. 1982 Jul;70(1):168–178. doi: 10.1172/JCI110590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gianturco S. H., Brown F. B., Gotto A. M., Jr, Bradley W. A. Receptor-mediated uptake of hypertriglyceridemic very low density lipoproteins by normal human fibroblasts. J Lipid Res. 1982 Sep;23(7):984–993. [PubMed] [Google Scholar]
  12. Goldstein J. L., Kita T., Brown M. S. Defective lipoprotein receptors and atherosclerosis. Lessons from an animal counterpart of familial hypercholesterolemia. N Engl J Med. 1983 Aug 4;309(5):288–296. doi: 10.1056/NEJM198308043090507. [DOI] [PubMed] [Google Scholar]
  13. Grundy S. M., Mok H. Y., Zech L., Steinberg D., Berman M. Transport of very low density lipoprotein triglycerides in varying degrees of obesity and hypertriglyceridemia. J Clin Invest. 1979 Jun;63(6):1274–1283. doi: 10.1172/JCI109422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Howard B. V., Davis M. P., Pettitt D. J., Knowler W. C., Bennett P. H. Plasma and lipoprotein cholesterol and triglyceride concentrations in the Pima Indians: distributions differing from those of Caucasians. Circulation. 1983 Oct;68(4):714–724. doi: 10.1161/01.cir.68.4.714. [DOI] [PubMed] [Google Scholar]
  15. Kannel W. B., Gordon T., Castelli W. P. Obesity, lipids, and glucose intolerance. The Framingham Study. Am J Clin Nutr. 1979 Jun;32(6):1238–1245. doi: 10.1093/ajcn/32.6.1238. [DOI] [PubMed] [Google Scholar]
  16. Kesaniemi Y. A., Grundy S. M. Increased low density lipoprotein production associated with obesity. Arteriosclerosis. 1983 Mar-Apr;3(2):170–177. doi: 10.1161/01.atv.3.2.170. [DOI] [PubMed] [Google Scholar]
  17. Kesäniemi Y. A., Beltz W. F., Grundy S. M. Comparisons of metabolism of apolipoprotein B in normal subjects, obese patients, and patients with coronary heart disease. J Clin Invest. 1985 Aug;76(2):586–595. doi: 10.1172/JCI112010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kissebah A. H., Alfarsi S., Adams P. W. Integrated regulation of very low density lipoprotein triglyceride and apolipoprotein-B kinetics in man: normolipemic subjects, familial hypertriglyceridemia and familial combined hyperlipidemia. Metabolism. 1981 Sep;30(9):856–868. doi: 10.1016/0026-0495(81)90064-0. [DOI] [PubMed] [Google Scholar]
  19. Knowler W. C., Pettitt D. J., Savage P. J., Bennett P. H. Diabetes incidence in Pima indians: contributions of obesity and parental diabetes. Am J Epidemiol. 1981 Feb;113(2):144–156. doi: 10.1093/oxfordjournals.aje.a113079. [DOI] [PubMed] [Google Scholar]
  20. Mahley R. W., Hui D. Y., Innerarity T. L., Weisgraber K. H. Two independent lipoprotein receptors on hepatic membranes of dog, swine, and man. Apo-B,E and apo-E receptors. J Clin Invest. 1981 Nov;68(5):1197–1206. doi: 10.1172/JCI110365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Markwell M. A., Haas S. M., Bieber L. L., Tolbert N. E. A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Anal Biochem. 1978 Jun 15;87(1):206–210. doi: 10.1016/0003-2697(78)90586-9. [DOI] [PubMed] [Google Scholar]
  22. Miettinen T. A. Cholesterol production in obesity. Circulation. 1971 Nov;44(5):842–850. doi: 10.1161/01.cir.44.5.842. [DOI] [PubMed] [Google Scholar]
  23. Nestel P. J., Whyte H. M. Plasma free fatty acid and triglyceride turnover in obesity. Metabolism. 1968 Dec;17(12):1122–1128. doi: 10.1016/0026-0495(68)90092-9. [DOI] [PubMed] [Google Scholar]
  24. Olefsky J., Reaven G. M., Farquhar J. W. Effects of weight reduction on obesity. Studies of lipid and carbohydrate metabolism in normal and hyperlipoproteinemic subjects. J Clin Invest. 1974 Jan;53(1):64–76. doi: 10.1172/JCI107560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Reaven G. M., Bernstein R. M. Effect of obesity on the relationship between very low density lipoprotein production rate and plasma triglyceride concentration in normal and hypertriglyceridemic subjects. Metabolism. 1978 Sep;27(9):1047–1054. doi: 10.1016/0026-0495(78)90150-6. [DOI] [PubMed] [Google Scholar]
  26. Sigurdsson G., Nicoll A., Lewis B. Conversion of very low density lipoprotein to low density lipoprotein. A metabolic study of apolipoprotein B kinetics in human subjects. J Clin Invest. 1975 Dec;56(6):1481–1490. doi: 10.1172/JCI108229. [DOI] [PMC free article] [PubMed] [Google Scholar]

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