Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-27T09:11:48.088Z Has data issue: false hasContentIssue false
  • English
  • Français

Lipoprotein metabolism in patients with anorexia nervosa: a case–control study investigating the mechanisms leading to hypercholesterolaemia

Published online by Cambridge University Press:  09 March 2007

T. Weinbrenner ,
M. Züger ,
G. E. Jacoby ,
S. Herpertz ,
R. Liedtke ,
T. Sudhop ,
I. Gouni-Berthold ,
M. Axelson  and
H. K. Berthold
T. Weinbrenner
Affiliation:
Department of Clinical Pharmacology, University of Bonn, 53105 Bonn, Germany
M. Züger
Affiliation:
Clinic Am Korso, 32545 Bad Oeynhausen, Germany
G. E. Jacoby
Affiliation:
Clinic Am Korso, 32545 Bad Oeynhausen, Germany
S. Herpertz
Affiliation:
Clinic for Psychotherapy and Psychosomatic Medicine, University of Essen, 45147 Essen, Germany
R. Liedtke
Affiliation:
Clinic and Policlinic for Psychosomatic Medicine and Psychotherapy, University of Bonn, 53105 Bonn, Germany
T. Sudhop
Affiliation:
Department of Clinical Pharmacology, University of Bonn, 53105 Bonn, Germany
I. Gouni-Berthold
Affiliation:
Medical Policlinic, University of Bonn, 53105 Bonn, Germany
M. Axelson
Affiliation:
Department of Clinical Chemistry, Karolinska Hospital, 17176 Stockholm, Sweden
H. K. Berthold*
Affiliation:
Department of Clinical Pharmacology, University of Bonn, 53105 Bonn, Germany
*
*Corresponding author: Professor H. K. Berthold, fax +49 221 4004 539, email heiner.berthold@akdae.de
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Hypercholesterolaemia is a common finding in patients with anorexia nervosa (AN). To investigate the type, frequency and pathophysiological mechanisms of changes in lipoprotein metabolism in AN we performed a cross-sectional study in fifty-eight female patients (mean age 24·2 years, BMI 15·3 (SD 1·5) kg/m2) and fifty-eight healthy age-matched controls (CO; BMI 22·2 (SD 1·7) kg/m2). Total cholesterol and LDL-cholesterol were higher in AN (5·5 (SD 1·3) v. 5·0 (SD 0·8) mmol/l, P=0·023; 3·6 (SD 1·1) v. 3·2 (SD 0·7) mmol/l, P=0·025 respectively). LDL particles were significantly more enriched in cholesterol and triacylglycerol in AN. In multiple regression analysis with LDL-cholesterol as the dependent and BMI, total body fat ( %), lathosterol:cholesterol ratio (endogenous cholesterol synthesis), 7α-hydroxy-4-cholesten-3-one (bile acid synthesis), non-esterified glycerol, free triiodothyronine and free thyroxine as independent variables, BMI was the only significant predictor in CO (R2 0·36, overall P=0·001). In AN the variability of LDL-cholesterol was significantly predicted by total body fat, free thyroxine, BMI, free triiodothyronine and non-esterified glycerol (R2 0·55, overall P<0·001). Subgroup analysis between restricting (AN-R) and binge-eating–purging patients (AN-B) indicated that in AN-R changes in lipoproteins, BMI and total body fat were more pronounced. AN-R patients had lower bile acid synthesis than AN-B (P=0·02). We conclude that elevated cholesterol concentrations in AN are generally due to an increase in LDL-cholesterol, which is mostly determined by the severe loss of body fat and the resulting changes in thyroid hormones, increased lipolysis and decreased endogenous cholesterol synthesis with resulting decrease in LDL removal. The clinical subtype of AN plays a major role in the mechanisms leading to hypercholesterolaemia.

Keywords

Anorexia nervosaLipoprotein metabolismHypercholesterolaemia
Type
Research Article
Information
British Journal of Nutrition , Volume 91 , Issue 6 , June 2004 , pp. 959 - 969
Copyright
Copyright © The Nutrition Society 2004

References

Affenito, SG, Lammi-Keefe, CJ, Vogel, S, Backstrand, JR, Welch, GW & Adams, CH (1997) Women with insulin-dependent diabetes mellitus (IDDM) complicated by eating disorders are at risk for exacerbated alterations in lipid metabolism. Eur J Clin Nutr 51, 462–466.CrossRefGoogle ScholarPubMed
Angelin, B (1991) Regulation of hepatic cholesterol metabolism in man. Ann Med 23, 177–180.CrossRefGoogle ScholarPubMed
Arden, MR, Weiselberg, EC, Nussbaum, MP, Shenker, IR & Jacobson, MS (1990) Effect of weight restoration on the dyslipoproteinemia of anorexia nervosa. J Adolesc Health Care 11, 199–202.Google Scholar
Auwerx, JStaels, B (1998) Leptin. Lancet 351, 737–742.Google Scholar
Axelson, M, Aly, A & Sjovall, J (1988) Levels of 7 alpha-hydroxy-4-cholesten-3-one in plasma reflect rates of bile acid synthesis in man. FEBS Lett 239, 324–328.CrossRefGoogle ScholarPubMed
Bertolotti, M, Spady, DK & Dietschy, JM, (1995) Regulation of hepatic cholesterol metabolism in the rat in vivo: effect of a synthetic fat-free diet on sterol synthesis and low-density lipoprotein transport. Biochim Biophys Acta 1255, 293–300.CrossRefGoogle ScholarPubMed
Björkhem, I, Miettinen, T, Reihner, E, Ewerth, S, Angelin, B & Einarsson, K (1987) Correlation between serum levels of some cholesterol precursors and activity of HMG-CoA reductase in human liver. J Lipid Res 28, 1137–1143.Google Scholar
Blendis, LM & Crisp, AH (1968) Serum cholesterol levels in anorexia nervosa. Postgrad Med J 44, 327–330.Google Scholar
Brown, MS & Goldstein, JL (1986) A receptor-mediated pathway for cholesterol homeostasis. Science 232, 34–47.CrossRefGoogle ScholarPubMed
Case, T, Lemieux, S, Kennedy, SH & Lewis, GF (1999) Elevated plasma lipids in patients with binge eating disorders are found only in those who are anorexic. Int J Eat Disord 25, 187–193.Google Scholar
Crisp, AH, Blendis, LM & Pawan, GL (1968) Aspects of fat metabolism in anorexia nervosa. Metabolism 17, 1109–1118.CrossRefGoogle ScholarPubMed
Crisp, AH, Lace, A, Blendis, LM & Pawan, GL (1967) Some aspects of fat metabolism in anorexia nervosa. Proc Nutr Soc 26, 32–35.Google Scholar
de Bruin, TW, Van Barlingen, H, Linde-Sibenius, TM, van Vuurst de Vries, AR, Akveld, MJ & Erkelens, DW (1993) Lipoprotein(a) and apolipoprotein B plasma concentrations in hypothyroid, euthyroid, and hyperthyroid subjects. J Clin Endocrinol Metab 76, 121–126.Google ScholarPubMed
Diekman, MJ, Anghelescu, N, Endert, E, Bakker, O & Wiersinga, WM (2000) Changes in plasma low-density lipoprotein (LDL)- and high-density lipoprotein cholesterol in hypo- and hyperthyroid patients are related to changes in free thyroxine, not to polymorphisms in LDL receptor or cholesterol ester transfer protein genes. J Clin Endocrinol Metab 85, 1857–1862.Google Scholar
Duvillard, L, Florentin, E, Lizard, G, Petit, JM, Galland, F, Monier, S, Gambert, P & Verges, B (2003) Cell surface expression of LDL receptor is decreased in type 2 diabetic patients and is normalized by insulin therapy. Diabetes Care 26, 1540–1544.Google Scholar
Feillet, F, Feillet-Choloudray, C, Bard, JM, Parra, HJ, Favre, EKabuth, B, Fruchart, JC & Vidailhet, M (2000) Plasma cholesterol and endogenous cholesterol synthesis during refeeding in anorexia nervosa. Clin Chim Acta 294, 45–56.Google Scholar
Gower, BA, Weinsier, RL, Jordan, JM, Hunter, GR & Desmond, R (2002) Effects of weight loss on changes in insulin sensitivity and lipid concentrations in premenopausal African American and white women. Am J Clin Nutr 76, 923–927.Google Scholar
Halmi, KA & Falk, JR (1981) Common physiological changes in anorexia nervosa. Int J Eat Disord 1, 27.3.0.CO;2-H>CrossRefGoogle Scholar
Homma, Y, Homma, K, Iizuka, S & Iigaya, K (2002) A case of anorexia nervosa with severe hyperlipoproteinemia. Int J Eat Disord 32, 121–124.Google Scholar
Kaye, WH, Weltzin, TE, Hsu, LK, McConaha, CW & Bolton, B (1993) Amount of calories retained after binge eating and vomiting. Am J Psychiatry 150, 969–971.Google ScholarPubMed
Kempen, HJ, Glatz, JF, Gevers Leuven, JA, van der Voort, HA & Katan, MB, (1988) Serum lathosterol concentration is an indicator of whole-body cholesterol synthesis in humans. J Lipid Res 29, 1149–1155.Google Scholar
Klinefelter, HF (1965) Hypercholesterolemia in anorexia nervosa. J Clin Endocrinol Metab 25, 1520–1521.CrossRefGoogle ScholarPubMed
Lacombe, CR, Corraze, GR, Nibbelink, MM, Boulze, D, Douste-Blazy, P & Camare, R (1986) Effects of a low-energy diet associated with egg supplementation on plasma cholesterol and lipoprotein levels in normal subjects: results of a cross-over study. Br J Nutr 56, 561–575.Google Scholar
Lin, DS & Connor, WE (1980) The long term effects of dietary cholesterol upon the plasma lipids, lipoproteins, cholesterol absorption, and the sterol balance in man: the demonstration of feedback inhibition of cholesterol biosynthesis and increased bile acid excretion. J Lipid Res 21, 1042–1052.Google Scholar
Mazzella, G, Cipolla, A, Villanova, N, Polimeni, C, Sipahi, A, Parini, P, Fusaroli, P, Festi, D & Roda, E, (1995) Changes in biliary lipid secretion and cholic acid kinetics induced by diet, diet plus simvastatin and diet plus ursodeoxycholic acid in obese subjects. Ital J Gastroenterol 27, 441–445.Google Scholar
Mehler, PS, Lezotte, D & Eckel, R (1998) Lipid levels in anorexia nervosa. Int J Eat Disord 24, 217–221.Google Scholar
Miettinen, TA (1968) Fecal steroid excretion during weight reduction in obese patients with hyperlipidemia. Clin Chim Acta 19, 341–344.CrossRefGoogle ScholarPubMed
Miettinen, TA, Tilvis, RS & Kesaniemi, YA (1990) Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population. Am J Epidemiol 131, 20–31.CrossRefGoogle ScholarPubMed
Montoye, HJ, Epstein, FH & Kjelsberg, MO (1966) Relationship between serum cholesterol and body fatness. An epidemiologic study. Am J Clin Nutr 18, 397–406.Google Scholar
Mordasini, R, Klose, G & Greten, H, (1978) Secondary type II hyperlipoproteinemia in patients with anorexia nervosa. Metabolism 27, 71–79.CrossRefGoogle ScholarPubMed
Nestel, PJ (1974) Cholesterol metabolism in anorexia nervosa and hypercholesterolemia. J Clin Endocrinol Metab 38, 325–328.Google Scholar
Phinney, SD, Tang, AB, Waggoner, CR, Tezanos-Pinto, RG & Davis, PA (1991) The transient hypercholesterolemia of major weight loss. Am J Clin Nutr 53, 1404–1410.Google Scholar
Regnstrom, J, Nilsson, J, Tornvall, P, Landou, C & Hamsten, A, (1992) Susceptibility to low-density lipoprotein oxidation and coronary atherosclerosis in man. Lancet 339, 1183–1186.CrossRefGoogle ScholarPubMed
Sanchez-Muniz, FJ, Marcos, A & Varela, P (1991) Serum lipids and apolipoprotein B values, blood pressure and pulse rate in anorexia nervosa. Eur J Clin Nutr 45, 33–36.Google Scholar
Savendahl, L & Underwood, LE (1999) Fasting increases serum total cholesterol, LDL cholesterol and apolipoprotein B in healthy, nonobese humans. J Nutr 129, 2005–2008.CrossRefGoogle ScholarPubMed
Stone, NJ (1994) Secondary causes of hyperlipidemia. Med Clin North Am 78, 117–141.CrossRefGoogle ScholarPubMed
Sullivan, PF, Gendall, KA, Bulik, CM, Carter, FA & Joyce, PR, (1998) Elevated total cholesterol in bulimia nervosa. Int J Eat Disord 23, 425–432.Google Scholar
Tamai, H, Mori, K, Matsubayashi, S, Kiyohara, K, Nakagawa, T, Okimura, MC, Walter, RM Jr, Kumagai, LF & Nagataki, S (1986) Hypothalamic–pituitary–thyroidal dysfunctions in anorexia nervosa. Psychother Psychosom 46, 127–131.Google Scholar
Teng, B, Thompson, GR, Sniderman, AD, Forte, TM, Krauss, RM & Kwiterovich, PO Jr (1983) Composition and distribution of low density lipoprotein fractions in hyperapobetalipoproteinemia, normolipidemia, and familial hypercholesterolemia. Proc Natl Acad Sci USA 80, 6662–6666.Google Scholar
Vaisman, N, Sklan, D & Dayan, Y (1990) Effect of moderate semi-starvation on plasma lipids. Int J Obes 14, 989–996.Google Scholar
van der Wal, AM, Bakker, O & Wiersinga, WM (1998) The decrease of liver LDL receptor mRNA during fasting is related to the decrease in serum T3. Int J Biochem Cell Biol 30, 209–215.Google Scholar
Wiegratz, I, Jung-Hoffmann, C, Gross, W & Kuhl, H (1998) Effect of two oral contraceptives containing ethinyl estradiol and gestodene or norgestimate on different lipid and lipoprotein parameters. Contraception 58, 83–91.Google Scholar
Zipfel, S, Lowe, B, Reas, DL, Deter, HC & Herzog, W (2000) Long-term prognosis in anorexia nervosa: lessons from a 21-year follow-up study. Lancet 355, 721–722.CrossRefGoogle ScholarPubMed
Zoppi, G, Cinquetti, M & Luciano, A (1993) Hypercholesterolemia in anorexia nervosa: probable cause. Acta Med Auxol 25, 201.Google Scholar