Hostname: page-component-78c5997874-t5tsf Total loading time: 0 Render date: 2024-11-10T04:07:48.423Z Has data issue: false hasContentIssue false
  • English
  • Français

Leptin Functioning in Eating Disorders

Published online by Cambridge University Press:  07 November 2014

Palmiero Monteleone ,
Antonio DiLieto ,
Eloisa Castaldo  and
Mario Maj
Get access Rights & Permissions [Opens in a new window]

Abstract

Leptin is an adipocyte-derived hormone, which is involved predominantly in the long-term regulation of body weight and energy balance by acting as a hunger suppressant signal to the brain. Leptin is also involved in the modulation of reproduction, immune function, physical activity, and some endogenous endocrine axes. Since anorexia nervosa (AN) and bulimia nervosa (BN) are characterized by abnormal eating behaviors, dysregulation of endogenous endocrine axes, alterations of reproductive and immune functions, and increased physical activity, extensive research has been carried out in the last decade in order to ascertain a role of this hormone in the pathophysiology of these syndromes. In this article, we review the available data on leptin physiology in patients with eating disorders. These data support the idea that leptin is not directly involved in the etiology of AN or BN. However, malnutrition-induced alterations in its physiology may contribute to the genesis and/or the maintenance of some clinical manifestations of AN and BN and may have an impact on the prognosis of AN.

Type
Review Articles
Information
CNS Spectrums , Volume 9 , Issue 7 , July 2004 , pp. 523 - 529
Copyright
Copyright © Cambridge University Press 2004

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Zhang, Y, Proenca, R, Maffei, M, Barone, M, Leopold, L, Friedman, JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–432.CrossRefGoogle ScholarPubMed
2.Farooqi, IS, Keogh, JM, Kamath, S, et al.Partial leptin deficiency and human adiposity. Nature. 2001;414:34–35.CrossRefGoogle ScholarPubMed
3.Kolaczynski, JW, Considine, RV, Ohannesian, J, et al. Responses of leptin to short-term fasting and refeeding in humans: a link with ketogenesis but not ketones themselves. Diabetes. 1996;45:1511–1515.CrossRefGoogle Scholar
4.Blundell, JE, Goodson, S, Halford, JCG. Regulation of appetite: role of leptin in signalling systems for drive and satiety. Int J Obes. 2001;25(suppl 1):529–534.CrossRefGoogle ScholarPubMed
5.Havel, PJ, Townsend, R, Chaump, L, Teff, K. High-fat meals reduce 24-h circulating leptin concentrations in women. Diabetes. 1999;48:334–341.CrossRefGoogle ScholarPubMed
6.Coleman, RA, Herrmann, TS. Nutritional regulation of leptin in humans. Diabetobgia. 1999;42:639–646.Google ScholarPubMed
7.Bouloumie, A, Drexler, HC, Lafontan, M, Busse, R. Leptin, the product of Ob gene, promotes angiogenesis. Circ Res. 1998;83:1059–1066.CrossRefGoogle Scholar
8.Fantuzzi, G, Faggioni, R. Leptin in the regulation of immunity, inflammation, and haematopoiesis. J Leukoc Biol. 2000;68:437–446.CrossRefGoogle Scholar
9.Moschos, S, Chan, JL, Mantzoros, CS. Leptin and reproduction: a review. Fertil Steril. 2002;77:433–444.CrossRefGoogle ScholarPubMed
10.Ahima, RS, Prabakaran, D, Mantzoros, C, et al. Role of leptin in the neuroendocrine response to fasting. Nature. 1996;382:250–252.CrossRefGoogle ScholarPubMed
11.Gruaz, NM, Lalaoui, M, Pierroz, DD, et al. Chronic administration of leptin into the lateral ventricle induces sexual maturation in severely food-restricted female rats. J Neuroendocrinol. 1998;10:627–633.CrossRefGoogle ScholarPubMed
12.Strobel, A, Issad, T, Camoin, L, Ozata, M, Strosberg, AD. A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet. 1998;18:213–215.CrossRefGoogle ScholarPubMed
13.Mantzoros, CS, Flier, JS, Rogol, AD. A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. V. Rising leptin levels may signal the onset of puberty. J Clin Endocrinol Metab. 1997;82:1066–1070.Google Scholar
14.Garcia-Mayor, RV, Andrade, MA, Rios, M, et al. Serum leptin levels in normal children: relationship to age, gender, body mass index, pituitary gonadal hormones, and pubertal stages. J Clin Endocrinol Metab. 1997;82: 849–2855.Google Scholar
15.Uotani, S, Bjorbaek, C, Tornoe, J, Flier, JS. Functional properties of leptin receptor isoforms. Internalization and degradation of leptin and ligand-induced receptor downregulation. Diabetes. 1999;48:279–286.CrossRefGoogle ScholarPubMed
16.Liu, C, Liu, XJ, Barry, G, Ling, N, Maki, RA, De Souza, EB. Expression and characterization of a putative high affinity human soluble leptin receptor. Endocrinology. 1997;138:3548–3554.CrossRefGoogle ScholarPubMed
17.Devos, R, Guisez, Y, Van der Heyden, J, et al. Ligand-independent dimerization of the extracellular domain of the leptin receptor and determination of the stoichiometry of leptin binding. J Biol Chem. 1997;272:18304–18310.CrossRefGoogle ScholarPubMed
18.Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Press; 1994.Google Scholar
19.Hebebrand, J, Blum, WF, Barth, N, et al. Leptin levels in patients with anorexia nervosa are reduced in the acute stage and elevated upon short-term weight restoration. Mol Psychiatry. 1997;2:330–334.CrossRefGoogle ScholarPubMed
20.Mantzoros, C, Flier, JS, Lesem, MD, Brewerton, TD, Jimerson, DC. Cerebrospinal fluid leptin in anorexia nervosa: correlation with nutritional status and potential role in resistance to weight gain. J Clin Endocrinol Metab. 1997;82:1845–1851.Google ScholarPubMed
21.Ferron, F, Considine, RV, Peino, R, et al. Serum leptin concentrations in patients with anorexia nervosa, bulimia nervosa and non-specific eating disorders correlate with the body mass index but are independent of the respective disease. Clin Endocrinol. 1997;46:289–293.CrossRefGoogle ScholarPubMed
22.Monteleone, P, Di Lieto, A, Tortorella, A, Longobardi, N, Maj, M. Circulating leptin in patients with anorexia nervosa, bulimia nervosa or binge-eating disorder: relationship to body weight, eating patterns, psychopathology and endocrine changes. Psychiatry Res. 2000;94:121–129.CrossRefGoogle ScholarPubMed
23.Monteleone, P, Fabrazzo, M, Tortorella, A, Fuschino, A, Maj, M. Opposite modifications in circulating leptin and soluble leptin receptor across the eating disorder spectrum. Mol Psychiatry. 2002;7:641–646.CrossRefGoogle ScholarPubMed
24.Monteleone, P, Martiadis, V, Colurcio, B, Maj, M. Leptin secretion is related to chronicity and severity of the illness in bulimia nervosa. Psychosom Med. 2002;64:874–879.Google ScholarPubMed
25.Holtkamp, K, Hebebrand, J, Mika, C, et al. The effect of therapeutically induced weight gain on plasma leptin levels in patients with anorexia nervosa. J Psychiat Res. 2003;37:165–169.CrossRefGoogle ScholarPubMed
26.Lob, S, Pickel, J, Bidlingmaier, M, Schaaf, L, et al. Serum leptin monitoring in anorectic patients during refeeding therapy. Exp Clin Endocrinol Diabetes. 2003;111:278–282.CrossRefGoogle ScholarPubMed
27.Holtkamp, K, Herpertz-Dahlmann, B, Mika, C, et al. Elevated physical activity and low leptin levels co-occur in patients with anorexia nervosa. J Clin Endocrinol Metab. 2003;88:5169–5174.CrossRefGoogle ScholarPubMed
28.Stoving, RK, Vinten, J, Handberg, A, et al. Diurnal variation of the serum leptin concentration in patients with anorexia nervosa. Clin Endocrinol. 1998;48:761–768.CrossRefGoogle ScholarPubMed
29.Gendall, KA, Kaye, WH, Altemus, M, McConaha, CW, La Via, MC. Leptin, neuropeptide Y, and peptide YY in long-term recovered eating disorder patients. Biol Psychiatry. 1999;46:292–299.CrossRefGoogle ScholarPubMed
30.Krizova, J, Papezova, H, Haluzikova, D, et al. Soluble leptin receptor levels in patients with anorexia nervosa. Endocr Res. 2002;28:199–205.CrossRefGoogle ScholarPubMed
31.Remschmidt, H, Schmidt, MH, Gutenbrunner, C. Prediction of long-term outcome in anorectic patients from longitudinal weight measurements during inpatient treatment: a cross validation study. In: Remschmidt, H, Schmidt, MH, eds. Child and Youth Psychiatry: European Perspectives. Vol 1. Anorexia Nervosa. Toronto, Canada: Hogrefe & Huber Publishers; 1990;150–167.Google Scholar
32.Kopp, W, Blum, WF, von Prittwitz, S, et al. Low leptin levels predict amenorrhea in underweight and eating disordered females. Mol Psychiatry. 1997;2:335–340.CrossRefGoogle ScholarPubMed
33.Ballauff, A, Ziegler, A, Emons, G, et al. Serum leptin and gonadotropin levels in patients with anorexia nervosa during weight gain. Mol Psychiatry. 1999;4:71–75.CrossRefGoogle ScholarPubMed
34.Holtkamp, K, Mica, C, Grzella, I, et al. Reproductive function during weight gain in anorexia nervosa. Leptin represents a metabolic gate to gonadotropin secretion. J Neural Transm. 2003;110:427–435.CrossRefGoogle ScholarPubMed
35.Brambilla, F, Monteleone, P, Bortolotti, F, et al. Persistent amenorrhoea in weight-recovered anorexics: psychological and biological aspects. Psychiatry Res. 2003;118:249–257.CrossRefGoogle ScholarPubMed
36.Wauters, M, Considine, RV, Van Gaal, LF. Human leptin: from an adipocyte hormone to an endocrine mediator. Eur J Endocrinol. 2000;143:293–311.CrossRefGoogle Scholar
37.Brambilla, F, Monteleone, P. Physical complications and physiological aberrations in eating disorders: a review. In: Maj, M, Halmi, K, Lopez-Ibor, JJ, Sartorius, N, eds. Eating Disorders. Chichester, England: Wiley & Sons Ltd; 2003;139–192.CrossRefGoogle Scholar
38.Goldstone, AP, Howard, JK, Lord, GM, et al. Leptin prevents the fall in plasma osteocalcin during starvation in male mice. Biochem Biophys Res Commun. 2002;295:475–481.CrossRefGoogle ScholarPubMed
39.Grinspoon, S, Thomas, L, Miller, K, Herzog, D, Klibanski, A. Effects of recombinant human IGF-I and oral contraceptive administration on bone density in anorexia nervosa. J Clin Endocrinol Metab. 2002;87:2883–2891.CrossRefGoogle Scholar
40.Bennett, BD, Solar, GP, Yuan, JQ, Mathias, J, Thomas, GR, Matthews, W. A role for leptin and its cognate receptor in haematopoiesis. Curr Biol. 1996;6:1170–1180;CrossRefGoogle Scholar
41.Faggioni, R, Feingold, KR, Grunfeld, C. Leptin regulation of the immune response and the immunodeficiency of malnutrition. FASEB J. 2001;15:2565–2571.CrossRefGoogle ScholarPubMed
42.Lord, GM, Matarese, G, Howard, JK, et al. Leptin modulated the T-cell immune response and reverses starvation-induced immunosuppression. Nature. 1998;394:897–901.CrossRefGoogle ScholarPubMed
43.Devuyst, O, Lambert, M, Rodhain, J, Lefehvre, C, Coche, E. Haematological changes and infectious complications in anorexia nervosa: a case-control study. Q J Med. 1993;86:791–799.Google ScholarPubMed
44.Davis, C, Katzam, DK, Kaptein, S, et al. The prevalence of high-level exercise in the eating disorders: etiological complications. Compr Psychiatry. 1997;38:321–326.CrossRefGoogle Scholar
45.Exner, C, Hebebrand, J, Remschmidt, H, et al. Leptin suppresses semi-starvation induced hyperactivity in rats: implications for anorexia nervosa. Mol Psychiatry. 2000;5:476–481.CrossRefGoogle ScholarPubMed
46.Monteleone, P, Bortolotti, F, Fabrazzo, M, La Rocca, A, Fuschino, A, Maj, M. Plasma leptin response to acute fasting and refeeding in untreated women with bulimia nervosa. J Clin Endocrinol Metab. 2000;85:2499–2503.CrossRefGoogle ScholarPubMed
47.Jimerson, DC, Mantzoros, C, Wolfe, BE, Metzger, ED. Decreased serum leptin in bulimia nervosa. J Clin Endocrinol Metab. 2000;85:4511–4514.Google ScholarPubMed
48.Brewerton, TD, Lesem, MD, Kennedy, A, Garvey, WT. Reduced plasma leptin concentrations in bulimia nervosa. Psychoneuroendocrinology. 2000;25:649–658.CrossRefGoogle ScholarPubMed
49.Nakai, Y, Hamagaki, S, Takagi, R, et al. Plasma concentrations of tumor necrosis factor-alpha (TNF-alpha) and soluble TNF receptors in patients with bulimia nervosa. Clin Endocrinol. 2000;53:383–388.CrossRefGoogle ScholarPubMed
50.Taylor, AE, Hubbard, J, Anderson, EJ. Impact of binge eating on metabolic and leptin dynamics in normal young women. J Clin Endocrinol Metab. 1999;84:428–434.Google ScholarPubMed
51.Karhunen, L, Haffner, S, Lappalainen, R, Turpeinen, A, Miettinen, H, Uusitupa, M. Serum leptin and short-term regulation of eating in obese women. Clin Sci (Lond). 1997; 92:573–578.CrossRefGoogle ScholarPubMed
52.Adami, GF, Campostano, A, Cella, F, et al. Serum leptin concentration in obese patients with binge eating disorder. Int J Obes Relat Disord. 2002;26:1125–1128.CrossRefGoogle ScholarPubMed
53.Monteleone, P, Martiadis, V, Fabrazzo, M, Serritella, C, Maj, M. Ghrelin and leptin responses to food ingestion in bulimia nervosa: implications for binge-eating and compensatory behaviours. Psychol Med. 2003;33:1387–1394.CrossRefGoogle ScholarPubMed
54.Geracioti, TD Jr, Liddle, RA. Impaired cholecystokinin secretion in bulimia nervosa. New Engl J Med. 1988;319:683–688.CrossRefGoogle ScholarPubMed