Classical Hormones Linked to Obesity

Chapter

Abstract

Hyperinsulinism, hypercortisolism, hypothyroidism, polycystic ovarian syndrome, and growth hormone deficiency are often associated with obesity. Insulin is a potent anabolic hormone. Treatment with insulin or some antidiabetic drugs results in weight gain through several mechanisms. Insulinoma is a rare cause of hyperinsulinism associated with hypoglycemia, hunger, and rapid weight gain. The etiology of polycystic ovary syndrome (PCOS) is complex and multifactorial. PCOS is often associated with central obesity, insulin resistance, and hyperandrogenemia. Excessive glucocorticoid exposure, such as Cushing’s syndrome, results in central obesity, sarcopenia, osteoporosis, hypertension, and hyperlipidemia.

Keywords

Lactate Lipase Arginine Dexamethasone Propranolol 

Notes

Acknowledgments

This work was supported by grants RO1-DK62348 and PO1-DK49210 from the National Institutes of Health.

References

  1. 1.
    Pessin, J. E., & Saltiel, A. R. (2000). Signaling pathways in insulin action: Molecular targets of insulin resistance. Journal of Clinical Investigation, 106(2), 165–169.CrossRefPubMedGoogle Scholar
  2. 2.
    Avruch, J., Khokhlatchev, A., Kyriakis, J. M., Luo, Z., Tzivion, G., Vavvas, D., et al. (2001). Ras activation of the Raf kinase: Tyrosine kinase recruitment of the MAP kinase cascade. Recent Progress in Hormone Research, 56, 127–155.CrossRefPubMedGoogle Scholar
  3. 3.
    Khan, A. H., & Pessin, J. E. (2002). Insulin regulation of glucose uptake: A complex interplay of intracellular signalling pathways. Diabetologia, 45(11), 1475–1483.CrossRefPubMedGoogle Scholar
  4. 4.
    Rossetti, L., & Giaccari, A. (1990). Relative contribution of glycogen synthesis and glycolysis to insulin-mediated glucose uptake. A dose-response euglycemic clamp study in normal and diabetic rats. Journal of Clinical Investigation, 85(6), 1785–1792.CrossRefPubMedGoogle Scholar
  5. 5.
    Guo, Z., Hensrud, D. D., Johnson, C. M., & Jensen, M. D. (1999). Regional postprandial fatty acid metabolism in different obesity phenotypes. Diabetes, 48(8), 1586–1592.CrossRefPubMedGoogle Scholar
  6. 6.
    Capeau, J. (2008). Insulin resistance and steatosis in humans. Diabetes & Metabolism, 34(6 Pt 2), 649–657.CrossRefGoogle Scholar
  7. 7.
    Nichols, G. A., & Gomez-Caminero, A. (2007). Weight changes following the initiation of new anti-hyperglycaemic therapies. Diabetes, Obesity & Metabolism, 9(1), 96–102.CrossRefGoogle Scholar
  8. 8.
    UK Prospective Diabetes Study (UKPDS) Group. (1998). Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet, 352(9131), 837–853.CrossRefGoogle Scholar
  9. 9.
    UK Prospective Diabetes Study (UKPDS) Group. (1998). Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet, 352(9131), 854–865.CrossRefGoogle Scholar
  10. 10.
    DCCT Research Group. (1988). Weight gain associated with intensive therapy in the diabetes control and complications trial. Diabetes Care, 11(7), 567–573.CrossRefGoogle Scholar
  11. 11.
    DCCT Research Group. (2001). Influence of intensive diabetes treatment on body weight and composition of adults with type 1 diabetes in the Diabetes Control and Complications Trial. Diabetes Care, 24(10), 1711–1721.CrossRefGoogle Scholar
  12. 12.
    Russell-Jones, D., & Khan, R. (2007). Insulin-associated weight gain in diabetes—Causes, effects and coping strategies. Diabetes, Obesity & Metabolism, 9(6), 799–812.CrossRefGoogle Scholar
  13. 13.
    Carver, C. (2006). Insulin treatment and the problem of weight gain in type 2 diabetes. Diabetes Educator, 32 (6), 910–917.CrossRefPubMedGoogle Scholar
  14. 14.
    Tucker, O. N., Crotty, P. L., & Conlon, K. C. (2006). The management of insulinoma. British Journal of Surgery, 93(3), 264–275.CrossRefPubMedGoogle Scholar
  15. 15.
    Grant, C. S. (2005). Insulinoma. Best Practice & Research. Clinical Gastroenterology, 19(5), 783–798.CrossRefGoogle Scholar
  16. 16.
    Malkoski, S. P., & Dorin, R. I. (1999). Composite glucocorticoid regulation at a functionally defined negative glucocorticoid response element of the human corticotropin-releasing hormone gene. Molecular Endocrinology, 13(10), 1629–1644.CrossRefPubMedGoogle Scholar
  17. 17.
    Watts, A. G. (2005). Glucocorticoid regulation of peptide genes in neuroendocrine CRH neurons: A complexity beyond negative feedback. Frontiers in Neuroendocrinology, 26(3–4), 109–130.CrossRefPubMedGoogle Scholar
  18. 18.
    Tata, J. R. (2002). Signalling through nuclear receptors. Nature Reviews. Molecular Cell Biology, 3(9), 702–710.CrossRefPubMedGoogle Scholar
  19. 19.
    Vegiopoulos, A., & Herzig, S. (2007). Glucocorticoids, metabolism and metabolic diseases. Molecular and Cellular Endocrinology, 275(1–2), 43–61.CrossRefPubMedGoogle Scholar
  20. 20.
    Newell-Price, J., Trainer, P., Besser, M., & Grossman, A. (1998). The diagnosis and differential diagnosis of Cushing’s syndrome and pseudo-Cushing’s states. Endocrine Reviews, 19(9), 647–672.CrossRefPubMedGoogle Scholar
  21. 21.
    Tsigos, C., & Chrousos, G. P. (1996). Differential diagnosis and management of Cushing’s syndrome. Annual Review of Medicine, 47, 443–461.CrossRefPubMedGoogle Scholar
  22. 22.
    Orth, D. N. (1995). Cushing’s syndrome. New England Journal of Medicine, 332(12), 791–803.CrossRefPubMedGoogle Scholar
  23. 23.
    Nieman, L. K. (2002). Diagnostic tests for Cushing’s syndrome. Annals of the New York Academy of Sciences, 970, 112–118.CrossRefPubMedGoogle Scholar
  24. 24.
    Flack, M. R., Oldfield, E. H., Cutler, G. B., Jr., Zweig, M. H., Malley, J.D., Chrousos, G. P., et al. (1992). Urine free cortisol in the high-dose dexamethasone suppression test for the differential diagnosis of the Cushing syndrome. Annals of Internal Medicine, 116(3), 211–217.PubMedGoogle Scholar
  25. 25.
    Gold, P. W., Loriaux, D. L., Roy, A., Kling, M. A., Calabrese, J. R., Kellner, C. H., et al. (1986). Responses to corticotropin-releasing hormone in the hypercortisolism of depression and Cushing’s disease. Pathophysiologic and diagnostic implications. New England Journal of Medicine, 314(21), 1329–1335.CrossRefPubMedGoogle Scholar
  26. 26.
    Tomlinson, J. W., & Stewart, P. M. (2007). Modulation of glucocorticoid action and the treatment of type-2 diabetes. Best Practice & Research. Clinical Endocrinology & Metabolism, 21, 607–619.CrossRefGoogle Scholar
  27. 27.
    Masuzaki, H., Paterson, J., Shinyama, H., Morton N. M., Mullins, J.J., Seckl, J. R., et al. (2001). A transgenic model of visceral obesity and the metabolic syndrome. Science, 294(5549), 2166–2170.CrossRefPubMedGoogle Scholar
  28. 28.
    Masuzaki, H., Yamamoto, H., Kenyon, C. J., Elmquist, J. K., Morton, N. M., Paterson, J. M., et al. (2003). Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in mice. Journal of Clinical Investigation, 112(1), 83–90.PubMedGoogle Scholar
  29. 29.
    Paterson, J. M., Morton, N. M., Fievet, C., Kenyon, C. J., Holmes, M. C., Staels, B., et al. (2004). Metabolic syndrome without obesity: Hepatic overexpression of 11beta-hydroxysteroid dehydrogenase type 1 in transgenic mice. Proceedings of the National Academy of Sciences of the United States of America, 101(18), 7088–7093.CrossRefPubMedGoogle Scholar
  30. 30.
    Kotelevtsev, Y., Holmes, M. C., Burchell, A., Houston, P. M., Schmoll. D., Jamieson, P., et al. (1997). 11Beta-hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid-inducible responses and resist hyperglycemia on obesity or stress. Proceedings of the National Academy of Sciences of the United States of America, 94(26), 14924–14929.CrossRefPubMedGoogle Scholar
  31. 31.
    Wake, D. J., & Walker, B. R. (2006). Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 in obesity. Endocrine, 29(1), 101–108.CrossRefPubMedGoogle Scholar
  32. 32.
    Valsamakis, G., Anwar, A., Tomlinsen, J. W., Shackleton, C. H., McTernan, P. G., Chetty, R., et al. (2004). 11Beta-hydroxysteroid dehydrogenase type 1 activity in lean and obese males with type 2 diabetes mellitus. Journal of Clinical Endocrinology and Metabolism, 89(9), 4755–4761.CrossRefPubMedGoogle Scholar
  33. 33.
    Yen, P. M. (2001). Physiological and molecular basis of thyroid hormone action. Physiological Review, 81(3), 1097–1142.Google Scholar
  34. 34.
    Shupnik, M. A., Ridgway, E. C., & Chin, W. W. (1989). Molecular biology of thyrotropin. Endocrine Reviews, 10(4), 459–475.CrossRefPubMedGoogle Scholar
  35. 35.
    Bianco, A. C., Salvatore, D., Gereben, B., Berry, M. J., & Larsen, P. R. (2002). Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocrine Reviews, 23(1), 38–89.CrossRefPubMedGoogle Scholar
  36. 36.
    Oetting, A., & Yen, P. M. (2007). New insights into thyroid hormone action. Best Practice & Research. Clinical Endocrinology & Metabolism, 21(2), 193–208.CrossRefGoogle Scholar
  37. 37.
    Liu, Y. Y., & Brent, G. A. (2009). Thyroid hormone crosstalk with nuclear receptor signaling in metabolic regulation. Trends in Endocrinology and Metabolism, 21(3), 166–173.CrossRefPubMedGoogle Scholar
  38. 38.
    Potenza, M., Via, M. A., & Yanagisawa, R. T. (2009). Excess thyroid hormone and carbohydrate metabolism. Endocrine Practice, 15, 254–262.PubMedGoogle Scholar
  39. 39.
    Hollowell, J. G., Staehling, N. W., Flanders, W. D., Hannon, W. H., Gunter, E. W., Spencer, C. A., et al. (2002). Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). Journal of Clinical Endocrinology and Metabolism, 87(2), 489–499.CrossRefPubMedGoogle Scholar
  40. 40.
    Vaidya, B., & Pearce, S. H. (2008). Management of hypothyroidism in adults. BMJ, 337, a801.CrossRefPubMedGoogle Scholar
  41. 41.
    Fatourechi, V. (2009). Subclinical hypothyroidism: An update for primary care physicians. Mayo Clinic Proceedings, 84(1), 65–71.CrossRefPubMedGoogle Scholar
  42. 42.
    Woeber, K. A. (2000). Update on the management of hyperthyroidism and hypothyroidism. Archives of Internal Medicine, 160(8), 1067–1071.CrossRefPubMedGoogle Scholar
  43. 43.
    Lania, A., Persani, L., & Beck-Peccoz, P. (2008). Central hypothyroidism. Pituitary, 11(2), 181–186.CrossRefPubMedGoogle Scholar
  44. 44.
    Al-Adsani, H., Hoffer, L. J., & Silva, J. E. (1997). Resting energy expenditure is sensitive to small dose changes in patients on chronic thyroid hormone replacement. Journal of Clinical Endocrinology and Metabolism, 82(4), 1118–1125.CrossRefPubMedGoogle Scholar
  45. 45.
    Boivin, M., Camirand, A., Carli, F., Hoffer, L. J., & Silva, J. E. (2000). Uncoupling protein-2 and -3 messenger ribonucleic acids in adipose tissue and skeletal muscle of healthy males: Variability, factors affecting expression, and relation to measures of metabolic rate. Journal of Clinical Endocrinology and Metabolism, 85(5), 1975–1983.CrossRefPubMedGoogle Scholar
  46. 46.
    Silva, J. E. (2003). The thermogenic effect of thyroid hormone and its clinical implications. Annals of Internal Medicine, 139(3), 205–213.PubMedGoogle Scholar
  47. 47.
    Knudsen, N., Laurberg, P., Rasmussen, L. B., Bulow, I., Perrild. H., Ovesen, L., et al. (2005). Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. Journal of Clinical Endocrinology and Metabolism, 90(7), 4019–4024.CrossRefPubMedGoogle Scholar
  48. 48.
    Nyrnes, A., Jorde, R., & Sundsfjord, J. (2006). Serum TSH is positively associated with BMI. International Journal of Obesity, 30(1), 100–105.CrossRefPubMedGoogle Scholar
  49. 49.
    Fox, C. S., Pencina, M. J., D’Agostino, R. B., Murabito, J.M., Seely, E. W., Pearce, E. N., et al. (2008). Relations of thyroid function to body weight: Cross-sectional and longitudinal observations in a community-based sample. Archives of Internal Medicine, 168(6), 587–592.CrossRefPubMedGoogle Scholar
  50. 50.
    Fazio, S., Palmieri, E. A., Lombardi, G., & Biondi, B. (2004). Effects of thyroid hormone on the cardiovascular system. Recent Progress in Hormone Research, 59, 31–50.CrossRefPubMedGoogle Scholar
  51. 51.
    Montenegro, J., Gonzalez, O., Saracho, R., Aguirre, R., & Martinez, I. (1996). Changes in renal function in primary hypothyroidism. American Journal of Kidney Diseases, 27(2), 195–198.CrossRefPubMedGoogle Scholar
  52. 52.
    Smith, T. J., Murata, Y., Horwitz, A. L., Philipson, L., & Refetoff, S. (1982). Regulation of glycosaminoglycan synthesis by thyroid hormone in vitro. Journal of Clinical Investigation, 70(5), 1066–1073.CrossRefPubMedGoogle Scholar
  53. 53.
    Gianoukakis, A. G., Jennings, T. A., King, C. S., Sheehan, C. E., Hoa, N., Heldin, P., et al. (2007). Hyaluronan accumulation in thyroid tissue: Evidence for contributions from epithelial cells and fibroblasts. Endocrinology, 148(1), 54–62.CrossRefPubMedGoogle Scholar
  54. 54.
    Meinhardt, U. J., & Ho, K. K. (2006). Modulation of growth hormone action by sex steroids. Clinical Endocrinology, 65(4), 413–422.CrossRefPubMedGoogle Scholar
  55. 55.
    Vance, M. L., & Mauras, N. (1999). Growth hormone therapy in adults and children. New England Journal of Medicine, 341(16), 1206–1216.CrossRefPubMedGoogle Scholar
  56. 56.
    Woelfle, J., Chia, D. J., Massart-Schlesinger, M. B., Moyano, P., & Rotwein, P. (2005). Molecular physiology, pathology, and regulation of the growth hormone/insulin-like growth factor-I system. Pediatric Nephrology, 20(3), 295–302.CrossRefPubMedGoogle Scholar
  57. 57.
    Shalet, S. M., Toogood, A., Rahim, A., & Brennan, B. M. (1998). The diagnosis of growth hormone deficiency in children and adults. Endocrine Reviews, 19(2), 203–223.CrossRefPubMedGoogle Scholar
  58. 58.
    Carroll, P. V., Christ, E. R., Bengtsson, B. A., Carlsson, L., Christiansen, J. S., Clemmons, D., et al. (1998). Growth hormone deficiency in adulthood and the effects of growth hormone replacement: A review. Growth Hormone Research Society Scientific Committee. Journal of Clinical Endocrinology and Metabolism, 83(2), 382–395.CrossRefPubMedGoogle Scholar
  59. 59.
    Gasco, V., Corneli, G., Rovere, S., Croce, C., Beccuti, G., Mainolfi, A., et al. (2008). Diagnosis of adult GH deficiency. Pituitary, 11(2), 121–128.CrossRefPubMedGoogle Scholar
  60. 60.
    Casanueva, F. F., Castro, A. I., Micic, D., Kelestimur, F., & Dieguez, C. (2009). New guidelines for the diagnosis of growth hormone deficiency in adults. Hormone Research, 71(Suppl 1), 112–115.CrossRefPubMedGoogle Scholar
  61. 61.
    Ho, K. K. (2007). Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: A statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia. European Journal of Endocrinology, 157(6), 695–700.CrossRefPubMedGoogle Scholar
  62. 62.
    Johannsson, G. (2009). Treatment of growth hormone deficiency in adults. Hormone Research, 71(Suppl 1), 116–122.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Division of Endocrinology, Diabetes and Metabolism, and the Institute for Diabetes, Obesity and MetabolismUniversity of Pennsylvania School of MedicinePhiladelphiaUSA

Personalised recommendations