Hostname: page-component-78c5997874-g7gxr Total loading time: 0 Render date: 2024-11-15T12:47:41.217Z Has data issue: false hasContentIssue false
  • English
  • Français

Hypothalamic-Pituitary-Adrenal Axis Function and the Metabolic Syndrome X of Obesity

Published online by Cambridge University Press:  07 November 2014

Baiju C. Gohil ,
Leonard A. Rosenblum ,
Jeremy D. Coplan  and
John G. Kral
Get access Rights & Permissions [Opens in a new window]

Abstract

Obesity has negative health consequences related to fat distribution, particularly the central or visceral accumulation of fat. The major complications associated with visceral obesity, termed the “Metabolic Syndrome of Obesity,” or “Syndrome X,” are type II diabetes, hypertension, and dyslipidemia. As with certain mood disorders, the syndrome may be a consequence of neuroendocrine perturbations typically associated with chronic stress. Our work with bonnet macaque monkeys provides an animal model for the relationship between early stress, behavioral and hypothalamic-pituitary-adrenal (HPA) axis dysregulation, and Syndrome X. During their infant's first half-year, mothers face a variable foraging demand (VFD), in which ample food varies unpredictably in the difficulty of its acquisition, and the offspring show persistent abnormalities in systems known to modulate stress and affective regulation. Early work on the bonnet macaque noted the emergence of a sample of spontaneously obese subjects as they matured. Using the VFD model, the current study showed that there was a clear relationship between early cerebrospinal fluid corticotropin-releasing factor levels and subsequently measured body mass index, supporting the hypotheses regarding the interactive roles of early experience and HPA axis dysregulation in the ontogeny of both metabolic and mood disorders.

Type
Feature Articles
Information
CNS Spectrums , Volume 6 , Issue 7: Novel Perspectives of Central CRF/HPA Axis Dysfunction , July 2001 , pp. 581 - 589
Copyright
Copyright © Cambridge University Press 2001

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. World Health Organization. Obesity: Preventing and Managing the Global Epidemic. Report of a WHO Consultation On Obesity. Geneva: World Health organization; 1998.Google Scholar
2. Holden, C. Mental health. Global survey examines impact of depression. Science. 2000;288:39–40.Google ScholarPubMed
3. Wallace, WJ, Sheslow, D, Hassink, S. Obesity in children: a risk for depression. Ann N Y Acad Sci. 1993;699:301–303.Google Scholar
4. Stunkard, AJ, Wadden, TA. Psychological aspects of severe obesity. Am J Clin Nutr. 1992;55:524S–532S.CrossRefGoogle ScholarPubMed
5. Stunkard, AJ, Harris, JR, Pedersen, NL, McClearn, GE. The body-mass index of twins who have been reared apart. N Engl J Med. 1990;322:1483–1487.CrossRefGoogle ScholarPubMed
6. Ravussin, E, Swinburn, BA. Pathophysiology of obesity. Lancet. 1992;340:404–408.CrossRefGoogle ScholarPubMed
7. 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.Google Scholar
8. Spitzer, RL, Yanovski, S, Wadden, T, et al. Binge eating disorder: its further validation in a multisite study. Int J Eat Disord. 1993;13:137–153.3.0.CO;2-#>CrossRefGoogle Scholar
9. Surwit, RS, Schneider, MS. Role of stress in the etiology and treatment of diabetes mellitus. Psychosom Med. 1993;55:380–393.CrossRefGoogle ScholarPubMed
10. McEwen, BS. Protective and damaging effects of stress mediators. N Engl J Med. 1998;338:171–179.CrossRefGoogle ScholarPubMed
11. Reaven, GM. Role of insulin resistance in human disease [Banting lecture 1988]. Diabetes. 1988;37:1595–1607.CrossRefGoogle ScholarPubMed
12. Bjorntorp, P, Rosmond, R. The metabolic syndrome-—a neuroendocrine disorder? Br J Nutr. 2000;83(Suppl 1):S49–S57.CrossRefGoogle ScholarPubMed
13. Chrousos, GP, Gold, PW. The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA. 1992;267:1244–1252.CrossRefGoogle ScholarPubMed
14. Friedman, TC, Mastorakos, G, Newman, TD, et al. Carbohydrate and lipid metabolism in endogenous hypercortisolism: shared features with metabolic syndrome X and NIDDM. Endocr J. 1996;43:645–655.CrossRefGoogle ScholarPubMed
15. Brown, PJ. The biocultural evolution of obesity: an anthropological view. In: Bjorntorp, P, Brodoff, B, eds. Obesity. Philadelphia, PA: Lippincott, Williams and Wilkins; 1992:330–339.Google Scholar
16. Kissebah, AH, Krakower, GR. Regional adiposity and morbidity. Physiol Rev. 1994;74:761–811.CrossRefGoogle ScholarPubMed
17. Vague, J. The degree of masculine differentiation of obesities: a factor determining predisposition to diabetes, atherosclerosis, gout, and uric calculous disease. Am J Clin Nutr. 1956;4:20–34.CrossRefGoogle ScholarPubMed
18. Hartz, AJ, Rupley, DC, Kalkhoff, RD, Rimm, AA. Relationship of obesity to diabetes: influence of obesity level and body fat distribution. Prev Med. 1983;12:351–357.CrossRefGoogle ScholarPubMed
19. NIH-NHLBI. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in adults. Washington, DC: Government Printing Office; 1998.Google Scholar
20. Pierson, RN. Quality of the Body Cell Mass: Body Composition in the Third Millennium. New York, NY: Springer-Verlag; 2000.CrossRefGoogle Scholar
21. Hansen, BC. The metabolic syndrome X. Ann N Y Acad Sci. 1999;892:1–24.Google Scholar
22. Bjorntorp, P. “Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis. 1990;10:493–496.CrossRefGoogle Scholar
23. Himsworth, HP. Diabetes mellitus: its differentiation into insulin sensitive and insulin insensitive types. Lincet. 1936;1:127–130.CrossRefGoogle Scholar
24. Festa, A, D'Agostino, R, Mykkanen, L, Tracy, R, Howard, BV, Haffner, SM. Low-density lipoprotein particle size is inversely related to plasminogen activator inhibitor-1 levels. The Insulin Resistance Atherosclerosis Study. Arterioscler Thromb Vase Biol. 1999;19:605–610.CrossRefGoogle ScholarPubMed
25. Rantala, AO, Kauma, H, Iilja, M, Savolainen, MJ, Reunanen, A, Kesaniemi, YA. Prevalence of the metabolic syndrome in drug-treated hypertensive patients and control subjects. J Intern Med. 1999;245:163–174.CrossRefGoogle ScholarPubMed
26. Considine, RV, Sinha, MK, Heiman, ML, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996;334:292–295.CrossRefGoogle ScholarPubMed
27. Bodkin, NL, Nicolson, M, Ortmeyer, HK, Hansen, BC. Hyperleptinemia: relationship to adiposity and insulin resistance in the spontaneously obese rhesus monkey. Horm Metab Res. 1996;28:674–678.CrossRefGoogle ScholarPubMed
28. Unger, RH, Zhou, YT, Orci, L. Regulation of fatty acid homeostasis in cells: novel role of leptin. Proc Natl Acad Sci U S A. 1999;96:2327–2332.CrossRefGoogle ScholarPubMed
29. Valencia, ME, Bennett, PH, Ravussin, E, Esparza, J, Fox, C, Schulz, LO. The Pima Indians in Sonora, Mexico. Nutr Rev. 1999;57(Suppl):S55–S58.CrossRefGoogle ScholarPubMed
30. Chrousos, GP. The role of stress and the hypothalamic-pituitary-adrenal axis in the pathogenesis of the metabolic syndrome: neuro-endocrine and target tissue-related causes. Int J Obes Relat Metab Disord. 2000;24(Suppl 2):S50–S55.CrossRefGoogle ScholarPubMed
31. Laudat, MH, Cerdas, S, Fournier, C, Guiban, D, Guilhaume, B, Luton, JP. Salivary cortisol measurement: a practical approach to assess pituitary-adrenal function. J Clin Endocrinol Metab. 1988;66:343–348.CrossRefGoogle ScholarPubMed
32. Rosmond, R, Lapidus, L, Bjorntorp, P. The influence of occupational and social factors on obesity and body fat distribution in middle-aged men. Int J Obes Relat Metab Disord. 1996;20:599–607.Google ScholarPubMed
33. Rosmond, R, Lapidus, L, Marin, P, Bjorntorp, P. Mental distress, obesity and body fat distribution in middle-aged men. Obes Res. 1996;4:245–252.CrossRefGoogle ScholarPubMed
34. Kral, JG, Buckley, MC, Kissileff, HR, Schaffner, F. Metabolic correlates of eating behavior in severe obesity. Int J Obes. 2001;25:258–264.CrossRefGoogle ScholarPubMed
35. Phillips, DI, Barker, DJ, Fall, CH, et al. Elevated plasma cortisol concentrations: a link between low birth weight and the insulin resistance syndrome? J Clin Endocrinol Metab. 1998;83:757–760.Google ScholarPubMed
36. Nemeroff, CB. The neurobiology of depression. Sci Am. 1998;278:42–49.CrossRefGoogle ScholarPubMed
37. Coplan, JD, Andrews, MW, Rosenblum, LA, et al. Persistent elevations of cerebrospinal fluid concentrations of corticotropin-releasing factor in adult nonhuman primates exposed to early-life stressors: implications for the pathophysiology of mood and anxiety disorders. Proc Natl Acad Sci U S A. 1996;93:1619–23.CrossRefGoogle ScholarPubMed
38. Sheline, YI, Sanghavi, M, Mintun, MA, Gado, MH. Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci. 1999;19:5034–5043.CrossRefGoogle Scholar
39. McEwen, BS, Seeman, T. Protective and damaging effects of mediators of stress. Elaborating and testing the concepts of allostasis and allostatic load. Ann N Y Acad Sci. 1999;896:30–47.Google Scholar
40. Weninger, SC, Dunn, AJ, Muglia, LJ, et al. Stress-induced behaviors require the corticotropin-releasing hormone (CRH) receptor, but not CRH. Proc Natl Acad Sci U S A. 1999;96:8283–8288.CrossRefGoogle Scholar
41. Kishimoto, T, Radulovic, J, Radulovic, M, et al. Deletion of CRHR2 reveals an anxiolytic role for corticotropin-releasing hormone receptor-2. Nat Genet. 2000;24:415–419.CrossRefGoogle ScholarPubMed
42. Hsu, SY, Hsueh, AJ. Human stresscopin and stress-copin-related peptide are selective ligands for the type 2 corticotropin-releasing hormone receptor. Nat Med. 2001;7:605–611.CrossRefGoogle ScholarPubMed
43. Campbell, CC. Food insecurity: a nutritional outcome or a predictor variable? J Nutr. 1991;121:408–415.CrossRefGoogle ScholarPubMed
44. Frongillo, EA Jr., Olson, CM, Rauschenbach, BS, Kendall, A. Nutritional Consequences of Food Insecurity in a Rural New York State County. Madison, WI: Institute for Research on Poverty, University of Wisconsin-Madison; 1997.Google Scholar
45. Rosenblum, LA, Paully, GS. The effects of varying environmental demands on maternal and infant behavior. Child Dev. 1984;55:305–314.CrossRefGoogle ScholarPubMed
46. Coplan, JD, Trost, RC, Owens, MJ, et al. Cerebrospinal fluid concentrations of somatostatin and biogenic amines in grown primates reared by mothers exposed to manipulated foraging conditions. Arch Gen Psychiatry. 1998;55:473–477.CrossRefGoogle ScholarPubMed
47. Coplan, JD, Smith, EL, Trost, RC, et al. Growth hormone response to clonidine in adversely reared young adult primates: relationship to serial cerebrospinal fluid corticotropin-releasing factor concentrations. Psychiatry Res. 2000;95:93–102.CrossRefGoogle ScholarPubMed
48. Bremner, JD, Licinio, J, Darnell, A, et al. Elevated CSF corticotropin-releasing factor concentrations in posttraumatic stress disorder. Am J Psychiatry. 1997;154:624–629.Google ScholarPubMed
49. Coplan, JD, Smith, ELRAltemus, M, et al. Variable foraging demand-rearing: sustained elevations in cisternal cerebrospinal fluid corticotropin releasing factor concentrations in adult primates. Biol Psychiatry. In press.Google Scholar
50. Jen, KL, Hansen, BC, Metzger, BL. Adiposity, anthropometric measures, and plasma insulin levels of rhesus monkeys. Int J Obes. 1985;9:213–224.Google ScholarPubMed
51. Richard, D, Rivest, R, Naimi, N, Timofeeva, E, Rivest, S. Expression of corticotropin-releasing factor and its receptors in the brain of lean and obese Zucker rats. Endocrinology. 1996;137:4786–4795.CrossRefGoogle ScholarPubMed
52. Bjorntorp, P. Metabolic implications of body fat distribution. Diabetes Care. 1991;14:1132–1143.CrossRefGoogle ScholarPubMed