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The metabolic syndrome — a neuroendocrine disorder?

Published online by Cambridge University Press:  09 March 2007

Per Björntorp*
Affiliation:
Department of Heart and Lung Diseases, University of Göteborg, Sahlgren's Hospital, S-413 45, Göteborg, Sweden
Roland Rosmond
Affiliation:
Department of Heart and Lung Diseases, University of Göteborg, Sahlgren's Hospital, S-413 45, Göteborg, Sweden
*
*Corresponding author: P. Björntorp, fax +46 31 826540, email per.bjorntorp@hjl.gu.se
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Abstract

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Central obesity is a powerful predictor for disease. By utilizing salivary cortisol measurements throughout the day, it has now been possible to show on a population basis that perceived stress-related cortisol secretion frequently is elevated in this condition. This is followed by insulin resistance, central accumulation of body fat, dyslipidaemia and hypertension (the metabolic syndrome). Socio-economic and psychosocial handicaps are probably central inducers of hyperactivity of the hypothalamic–pituitary adrenal (HPA) axis. Alcohol, smoking and traits of psychiatric disease are also involved. In a minor part of the population a dysregulated, depressed function of the HPA axis is present, associated with low secretion of sex steroid and growth hormones, and increased activity of the sympathetic nervous system. This condition is followed by consistent abnormalities indicating the metabolic syndrome. Such ‘burned-out’ function of the HPA axis has previously been seen in subjects exposed to environmental stress of long duration. The feedback control of the HPA axis by central glucocorticoid receptors (GR) seems inefficient, associated with a polymorphism in the 5′ end of the GR gene locus. Homozygotes constitute about 14 % of Swedish men (women to be examined). Such men have a poorly controlled cortisol secretion, abdominal obesity, insulin resistance and hypertension. Furthermore, polymorphisms have been identified in the regulatory domain of the GR gene that are associated with elevated cortisol secretion; polymorphisms in dopamine and leptin receptor genes are associated with sympathetic nervous system activity, with elevated and low blood pressure, respectively. These results suggest a complex neuroendocrine background to the metabolic syndrome, where the kinetics of the regulation of the HPA axis play a central role.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2000

References

Björntorp, P (1990) ‘Portal’ adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 10, 493496.CrossRefGoogle Scholar
Björntorp, P (1993) Visceral obesity: a ‘Civilization Syndrome’. Obesity Research 1, 216222.CrossRefGoogle ScholarPubMed
Björntorp, P (1996) The regulation of adipose tissue distribution in humans. International Journal of Obesity and Related Metabolic Disorders 20, 291302.Google ScholarPubMed
Björntorp, P (1999) Overweight is risking fate. Best Practice and Research in Clinical Endocrinology and Metabolism 13, 4769.CrossRefGoogle ScholarPubMed
Björntorp, P (1999) Neuroendocrine perturbations as a cause of insulin resistance Diabetes/ Metabolism Research and Reviews.3.0.CO;2-C>CrossRefGoogle Scholar
Björntorp, P, Holm, G & Rosmond, R (1999) Hypothalamic arousal, insulin resistance and type 2 diabetes mellitus. Diabetic Medicine 16, 373383.CrossRefGoogle ScholarPubMed
Bouchard, C & Perusse, L (1996) Current status of the human obesity gene map. Obesity Research 4, 8190.CrossRefGoogle ScholarPubMed
Brunner, EJ, Marmot, MG, Nanchahal, K, Shipley, MJ, Stansfield, SA, Juneja, M & Alberti, KGMM (1997) Social inequality in coronary risk: central obesity and the metabolic syndrome. Evidence from the Whitehall II study. Diabetologia 10, 13411349.CrossRefGoogle Scholar
Buemann, B, Vohl, M-C, Chagnon, M, Chagnon, YC, Gagnon, J, Perusse, L, Dionne, F, Despres, J-P, Tremblay, A, Nadeau, A & Bouchard, C (1997) Abdominal visceral fat is associated with a Bcl I restriction fragment length polymorphism at the glucocorticoid receptor gene locus. Obesity Research 5, 186192.CrossRefGoogle Scholar
Calogero, AE, Callucci, WT, Gold, PW & Chrousos, GP (1998) Multiple regulatory feedback loops on hypothalamic-corticotropin releasing hormone secretion. Journal of Clinical Investigation 82, 7698.Google Scholar
Chrousos, GP & Gold, PW (1992) The concept of stress and stress system disorders: overview of physical and behavioral homeostasis. Journal of the American Medical Association 267, 12441252.CrossRefGoogle ScholarPubMed
Dallman, MF, Akana, SF, Scribner, KA, Bradbury, MJ, Walker, C-D, Strack, AM & Cascio, CS (1992) Stress, feedback and facilitation in the hypothalamo-pituitary adrenal axis. Journal of Neuroendocrinology 4, 517526.CrossRefGoogle ScholarPubMed
Dunbar, JC, Hu, Y & Lu, H (1997) Intracerebroventricular leptin increases lumbar and renal nerve activity and blood pressure in normal rats. Diabetes 46, 20402045.CrossRefGoogle ScholarPubMed
Eriksson, E & & Humble, M (1990) Serotonin in psychiatric pathophysiology. The Biological Basis for Psychopharmacological Treatment. Progress in Basic and Clinical Pharmacology, pp. 66119 [R, Pohl, S, Gerson, editors]. Basel, Switzerland: Karger.Google Scholar
Folkow, B (1993) Physiological organization of neurohormonal responses to psychosocial stimuli. Implications for health and disease. Annals of Behavioural Medicine 15, 236244.Google Scholar
Haynes, WG, Morgan, DA, Walsh, SA, Mark, AL & Sivitz, WI (1997) Receptor mediated regional sympathetic nerve activation by leptin. Journal of Clinical Investigation 100, 270278.CrossRefGoogle ScholarPubMed
Kirschbaum, C & Hellhammer, DH (1994) Salivary cortisol in psychoneuroendocrine research: recent developments and applications. Psychoneuroendocrinology 19, 313333.CrossRefGoogle ScholarPubMed
Kissebah, AHKrakower, GRSonnenberg, G & Hermes, MMI (1998) Clinical manifestations of the metabolic syndrome. In Handbook of Obesity, pp. 601636 [GA, Bray, C, Bouchard and CPT, James, editors]. New York: Marcel Dekker.Google Scholar
Kretschmer, E (1921) Körperbau und Character, 1st edn. Berlin: Springer (1967, 25th edn).Google Scholar
Linkowski, P, Van Onderbergen, A, Kerkhofs, M, Bosson, D, Mendlewics, J, Van Cauter, E (1993) Twin study of 24-h cortisol profile: evidence for genetic control of the human circadian clock. American Journal of Physiology 264, 173181.Google ScholarPubMed
Ljung, T, Andersson, B, Bengtsson, B-Å, Björntorp, P, Mårin, P (1996) Inhibition of cortisol secretion by dexamethasone in relation to body fat distribution: a dose–response study. Obesity Research 4, 277282.CrossRefGoogle ScholarPubMed
McEwen, BS (1998) Protective and damaging effects of stress mediators. New England Journal of Medicine 338, 171179.CrossRefGoogle ScholarPubMed
Missale, C, Russel Nash, S, Robinson, SW, Jaber, M & Caron, MG (1998) Dopamine receptors: from structure to function. Physiological Reviews 78, 189–122.CrossRefGoogle ScholarPubMed
Randle, P, Garland, P, Hales, N & Newsholme, E (1963) The glucose fatty acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus Lancet 785789.CrossRefGoogle Scholar
Reaven, GM (1988) Role of insulin resistance in human disease. Diabetes 37, 15951607.CrossRefGoogle ScholarPubMed
Riggins, GJ, Lokey, KL, Chastain, JL, Leiner, HA, Sherman, SL, Wilkinson, KD & Warren, ST (1992) Human genes containing trinucleotide repeats. Nature Genetics 2, 186191.CrossRefGoogle ScholarPubMed
Rosmond, R, Björntorp, P (1999) Occupational status, cortisol secretory pattern and visceral obesity in middle-aged men Journal of Internal Medicine.Google Scholar
Rosmond, R, Dallman, MF, Björntorp, P (1998) Stress-related cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities. Journal of Clinical Endocrinology and Metabolism 83, 853859.Google ScholarPubMed
Rosmond, R, Holm, G, Björntorp, P (1999) Food-induced cortisol secretion in relation to anthropometric, metabolic and hemodynamic variables in men International Journal of Obesity and Related Metabolic Disorders.CrossRefGoogle Scholar
Rosmond, R, Chagnon, YC, Holm, G, Chagnon, M, Perusse, L, Carlsson, B, Bouchard, C, Björntorp, P (1999) A Bcl I restriction fragment length polymorphism of the glucocorticoid receptor gene locus is associated with abdominal obesity and dysregulation of the hypothalamic–pituitary-adrenal axis Obesity Research.Google Scholar
Shively, CA, Laber-Laird, K & Auton, RF (1997) Behavior and physiology of social stress and depression in female Cynomolgus monkeys. Biological Psychiatry 41, 871882.CrossRefGoogle ScholarPubMed
Smyth, J, Ockenfels, MC, Porter, L, Kirschbaum, C, Hellhammer, DH & Stone, AA (1998) Stressors and mood measured on a momentary basis are associated with salivary cortisol secretion. Psychoneuroendocrinology 23, 353370.CrossRefGoogle ScholarPubMed
Vague, J (1947) La différentiaton sexuelle. Facteur déterminant des formes de l'obésité. Presse Medical 55, 339341.Google Scholar
Watts, GCH, Harrap, SB, Foy, CJW, Holton, DW, Edwards, HV, Davidsson, HR, Connor, JM, Lever, AF & Fraser, R (1992) Abnormalities of glucocorticoid metabolism and reninangiotensin system: a four-corners approach to the identification of genetic determinants of blood pressure. Journal of Hypertension 10, 473482.CrossRefGoogle Scholar
Weaver, JU, Hitman, GA & Kopelman, PG (1992) An association between a Bcl I restriction fragment length polymorphism of the glucocorticoid receptor locus and hyperinsulinemia in obese women. Journal of Molecular Endocrinology 9, 295300.CrossRefGoogle Scholar
WHO (1998) Obesity. Preventing and Managing the Global Epidemic. Report of WHO consultation on obesity,Geneva,June, 1997.Google Scholar