Treatments in Endocrinology

, Volume 3, Issue 5, pp 269–277

Circuitries Involved in the Control of Energy Homeostasis and the Hypothalamic-Pituitary-Adrenal Axis Activity

Leading Article

Abstract

The regulation of bodyweight is a complex process involving the interplay of neuronal circuitries controlling food intake and energy expenditure (thermogenesis) with endocrine secretions modulating the activity of the neurons making up those circuitries. The neurons controlling food intake and thermogenesis also modulate the hypothalamic-pituitary-adrenal axis, the role of which in the regulation of energy balance has been acknowledged for some time. These neurons secrete various neuromolecules or neuropeptides including endocannabinoids, neuropeptide Y, agouti-related protein, melanin-concentrating hormone, orexins (hypocretins), melanocortins, cocaine- and amphetamine-regulated transcript, thyrotropin-releasing hormone, corticotropin-releasing hormone, and urocortins. Among those peptides, neuropeptide Y, agouti-related peptide, melanin-concentrating hormone, orexins, and endocannabinoids have been classified as being anabolic molecules whereas melanocortins, cocaine- and amphetamine-regulated transcript, thyrotropin-releasing hormone, and corticotropin-releasing hormone are referred to as catabolic peptides. The expression and secretion of these neuromolecules are known to be affected by the anabolic (corticosteroids and ghrelin) and catabolic (leptin, insulin, and glucagon-like peptide 1) peripheral hormones. A link is made between the pathways regulating energy balance and those modulating the activity of the hypothalamic-pituitary-adrenal axis.

References

  1. 1.
    Kopelman PG. Obesity as a medical problem. Nature 2000; 404: 635–43PubMedGoogle Scholar
  2. 2.
    Despres JP. Drug treatment for obesity: we need more studies in men at higher risk of coronary events. BMJ 2001; 322: 1379–80PubMedCrossRefGoogle Scholar
  3. 3.
    Strack AM, Bradbury MJ, Dallman MF. Corticosterone decreases nonshivering thermogenesis and increases lipid storage in brown adipose tissue. Am J Physiol Regul Integr Comp Physiol 1995; 37: R183–91Google Scholar
  4. 4.
    Galpin KS, Henderson RG, James WPT, et al. GDP binding to brown-adiposetissue mitochondria of mice treated chronically with corticosterone. Biochem J 1983; 214: 265–8PubMedGoogle Scholar
  5. 5.
    Arvaniti K, Ricquier D, Champigny O, et al. Leptin and corticosterone have opposite effects on food intake and the expression of UCP1 mRNA in brown adipose tissue of lep(ob)/lep(ob) mice. Endocrinology 1998; 139: 4000–4PubMedCrossRefGoogle Scholar
  6. 6.
    Strack AM, Sebastian RJ, Schwartz MW, et al. Glucocorticoids and insulin: reciprocal signals for energy balance. Am J Physiol Regul Integr Comp Physiol 1995; 37: R142–9Google Scholar
  7. 7.
    Pasquali R, Vicennati V. The abdominal obesity phenotype and insulin resistance are associated with abnormalities of the hypothalamic-pituitary-adrenal axis in humans. Horm Metab Res 2000; 32: 521–5PubMedCrossRefGoogle Scholar
  8. 8.
    Ueland T, Kristo C, Godang K, et al. Interleukin-1 receptor antagonist is associated with fat distribution in endogenous Cushing’s syndrome: a longitudinal study. J Clin Endocrinol Metab 2003; 88: 1492–6PubMedCrossRefGoogle Scholar
  9. 9.
    Timofeeva E, Richard D. Functional activation of CRH neurons and expression of the genes encoding CRH and its receptors in food-deprived lean (Fa/?.) and obese (fa/fa) Zucker rats. Neuroendocrinology 1997; 66: 327–40PubMedCrossRefGoogle Scholar
  10. 10.
    Alarrayed F, Hartman AD, Porter JR. Is there a role for the adrenals in the development of hypercholesterolemia in Zucker fatty rats. Am J Physiol 1992; 263: E287–95PubMedGoogle Scholar
  11. 11.
    Guillaume-Gentil C, Rohner-Jeanrenaud F, Abramo F, et al. Abnormal regulation of the hypothalamo-pituitary-adrenal axis in the genetically obese fa/fa rat. Endocrinology 1990; 126: 1873–9PubMedCrossRefGoogle Scholar
  12. 12.
    Tsai HJ, Romsos DR. Glucocorticoid and mineralocorticoid receptor-binding characteristics in obese (ob/ob) mice. Am J Physiol 1991; 261: E495–9PubMedGoogle Scholar
  13. 13.
    McGinnis R, Walker J, Margules D, et al. Dysregulation of the hypothalamus-pituitary-adrenal axis in male and female, genetically obese (ob/ob) mice. J Neuroendocrinol 1992; 4: 765–71PubMedCrossRefGoogle Scholar
  14. 14.
    White BD, Corll CB, Porter JR. The metabolic clearance rate of corticosterone in lean and obese male Zucker rats. Metabolism 1989; 38: 530–6PubMedCrossRefGoogle Scholar
  15. 15.
    Vettor R, Vicennati V, Gambineri A, et al. Leptin and the hypothalamic-pituitary-adrenal axis activity in women with different obesity phenotypes. Int J Obes 1997; 21: 708–11CrossRefGoogle Scholar
  16. 16.
    Bjorntorp P, Rosmond R. Obesity and cortisol. Nutrition 2000; 16: 924–36PubMedCrossRefGoogle Scholar
  17. 17.
    Schwartz MW, Woods SC, Porte Jr D, et al. Central nervous system control of food intake. Nature 2000; 404: 661–71PubMedGoogle Scholar
  18. 18.
    Elmquist JK. Anatomic basis of leptin action in the hypothalamus. Front Horm Res 2000; 26: 21–41PubMedCrossRefGoogle Scholar
  19. 19.
    Cone RD. The central melanocortin system and energy homeostasis. Trends Endocrinol Metab 1999; 10: 211–6PubMedCrossRefGoogle Scholar
  20. 20.
    Richard D. The role of CRF in the regulation of energy balance. Curr Opin Endocrinol Diabetes 1999; 6: 10–8CrossRefGoogle Scholar
  21. 21.
    Sleeman MW, Anderson KD, Lambert PD, et al. The ciliary neurotrophic factor and its receptor, CNTFR alpha. Pharm Acta Helv 2000; 74: 265–72PubMedCrossRefGoogle Scholar
  22. 22.
    Williams G, Harrold JA, Cutler DJ. The hypothalamus and the regulation of energy homeostasis: lifting the lid on a black box. Proc Nutr Soc 2000; 59: 385–96PubMedCrossRefGoogle Scholar
  23. 23.
    Woods SC, Schwartz MW, Baskin DG, et al. Food intake and the regulation of body weight. Annu Rev Psychol 2000; 51: 255–77PubMedCrossRefGoogle Scholar
  24. 24.
    Stanley SA, Small CJ, Murphy KG, et al. Actions of cocaine- and amphetamine-regulated transcript (CART) peptide on regulation of appetite and hypothalamo-pituitary axes in vitro and in vivo in male rats. Brain Res 2001; 893: 186–94PubMedCrossRefGoogle Scholar
  25. 25.
    Vrang N, Larsen PJ, Kristensen P, et al. Central administration of cocaine-amphetamine-regulated transcript activates hypothalamic neuroendocrine neurons in the rat. Endocrinology 2000; 141: 794–801PubMedCrossRefGoogle Scholar
  26. 26.
    Hanson ES, Dallman MF. Neuropeptide y (NPY) may integrate responses of hypothalamic feeding systems and the hypothalamo-pituitary-adrenal axis. J Neuroendocrinol 1995; 7: 273–9PubMedCrossRefGoogle Scholar
  27. 27.
    Kuru M, Ueta Y, Serino R, et al. Centrally administered orexin/hypocretin activates HPA axis in rats. Neuroreport 2000; 11: 1977–80PubMedCrossRefGoogle Scholar
  28. 28.
    Bluet-Pajot MT, Presse F, Vokö Z, et al. Neuropeptide-E-I antagonizes the action of melanin-concentrating hormone on stress-induced release of adrenocorticotropin in the rat. J Neuroendocrinol 1995; 7: 297–303PubMedCrossRefGoogle Scholar
  29. 29.
    Johnson KM, Dewey WL, Ritter KS, et al. Cannabinoid effects on plasma corticosterone and uptake of 3H-corticosterone by mouse brain. Eur J Pharmacol 1978; 47: 303–10PubMedCrossRefGoogle Scholar
  30. 30.
    Weidenfeld J, Feldman S, Mechoulam R. Effect of the brain constituent anandamide, a cannabinoid receptor agonist, on the hypothalamo-pituitary-adrenal axis in the rat. Neuroendocrinology 1994; 59: 110–2PubMedCrossRefGoogle Scholar
  31. 31.
    Papadopoulos AD, Wardlaw SL. Endogenous alpha-MSH modulates the hypothalamic-pituitary-adrenal response to the cytokine interleukin-1beta. J Neuroendocrinol 1999; 11: 315–9PubMedCrossRefGoogle Scholar
  32. 32.
    Mountjoy KG, Wong J. Obesity, diabetes and functions for proopiomelanocortinderived peptides. Mol Cell Endocrinol 1997; 128: 171–7PubMedCrossRefGoogle Scholar
  33. 33.
    Wikberg JES. Melanocortin receptors: new opportunities in drug discovery. Expert Opin Ther Patents 2001; 11: 61–76CrossRefGoogle Scholar
  34. 34.
    Chen AS, Marsh DJ, Trumbauer ME, et al. Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat Genet 2000; 26: 97–102PubMedCrossRefGoogle Scholar
  35. 35.
    Huszar D, Lynch CA, Fairchild-Huntress V, et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 1997; 88: 131–41PubMedCrossRefGoogle Scholar
  36. 36.
    Lu D, Willard D, Patel IR, et al. Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor. Nature 1994; 371: 799–802PubMedCrossRefGoogle Scholar
  37. 37.
    Hagan MM, Benoit SC, Rushing PA, et al. Immediate and prolonged patterns of agouti-related peptide-(83–132)-induced c-Fos activation in hypothalamic and extrahypothalamic sites. Endocrinology 2001; 142: 1050–6PubMedCrossRefGoogle Scholar
  38. 38.
    Hahn TM, Breininger JF, Baskin DG, et al. Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons. Nat Neurosci 1998; 1: 271–2PubMedCrossRefGoogle Scholar
  39. 39.
    Shutter JR, Graham M, Kinsey AC, et al. Hypothalamic expression of ART, a novel gene related to agouti, is up-regulated in obese and diabetic mutant mice. Genes Dev 1997; 11: 593–602PubMedCrossRefGoogle Scholar
  40. 40.
    Mizuno TM, Mobbs CV. Hypothalamic agouti-related protein messenger ribonucleic acid is inhibited by leptin and stimulated by fasting. Endocrinology 1999; 140: 814–7PubMedCrossRefGoogle Scholar
  41. 41.
    DiMarzo V, Goparaju SK, Wang L, et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 2001; 410: 822–5CrossRefGoogle Scholar
  42. 42.
    Bisogno T, Berrendero F, Ambrosino G, et al. Brain regional distribution of endocannabinoids: implications for their biosynthesis and biological function. Biochem Biophys Res Commun 1999; 256: 377–80PubMedCrossRefGoogle Scholar
  43. 43.
    Pertwee RG. Pharmacology of cannabinoid receptor ligands. Curr Med Chem 1999; 6: 635–64PubMedGoogle Scholar
  44. 44.
    Zuardi AW, Teixeira NA, Karniol IC. Pharmacological interaction of the effects of delta 9-trans-tetrahydrocannabinol and cannabidiol on serum corticosterone levels in rats. Arch Int Pharmacodyn Ther 1984; 269: 12–9PubMedGoogle Scholar
  45. 45.
    Manzanares J, Corchero J, Fuentes JA. Opioid and cannabinoid receptor-mediated regulation of the increase in adrenocorticotropin hormone and corticosterone plasma concentrations induced by central administration of delta(9)-tetrahydro-cannabinol in rats. Brain Res 1999; 839: 173–9PubMedCrossRefGoogle Scholar
  46. 46.
    Wenger T, Jamali KA, Juaneda C, et al. Arachidonyl ethanolamide (anandamide) activates the parvocellular part of hypothalamic paraventricular nucleus. Biochem Biophys Res Commun 1997; 237: 724–8PubMedCrossRefGoogle Scholar
  47. 47.
    Hao S, Avraham Y, Mechoulam R, et al. Low dose anandamide affects food intake, cognitive function, neurotransmitter and corticosterone levels in diet-restricted mice. Eur J Pharmacol 2000; 392: 147–56PubMedCrossRefGoogle Scholar
  48. 48.
    Di S, Malcher-Lopes R, Halmos KC, et al. Nongenomic glucocorticoid inhibition via endocannabinoid release in the hypothalamus: a fast feedback mechanism. J Neurosci 2003; 23: 4850–7PubMedGoogle Scholar
  49. 49.
    Sakurai T, Amemiya A, Ishii M, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 1998; 92: 573–85PubMedCrossRefGoogle Scholar
  50. 50.
    de Lecea L, Kilduff TS, Peyron C, et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 1998; 95: 322–7PubMedCrossRefGoogle Scholar
  51. 51.
    Chemelli RM, Willie JT, Sinton CM, et al. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 1999; 98: 437–51PubMedCrossRefGoogle Scholar
  52. 52.
    Peyron C, Tighe DK, van den Pol AN, et al. Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 1998; 18: 9996–10015PubMedGoogle Scholar
  53. 53.
    Cutler DJ, Morris R, Sheridhar V, et al. Differential distribution of orexin-A and orexin-B immunoreactivity in the rat brain and spinal cord. Peptides 1999; 20: 1455–70PubMedCrossRefGoogle Scholar
  54. 54.
    Marcus JN, Aschkenasi CJ, Lee CE, et al. Differential expression of orexin receptors 1 and 2 in the rat brain. J Comp Neurol 2001; 435: 6–25PubMedCrossRefGoogle Scholar
  55. 55.
    Sweet DC, Levine AS, Billington CJ, et al. Feeding response to central orexins. Brain Res 1999; 821: 535–8PubMedCrossRefGoogle Scholar
  56. 56.
    Timofeeva E, Picard F, Duclos M, et al. Neuronal activation and corticotropin-releasing hormone expression in the brain of obese (fa/fa) and lean (fa/?.) Zucker rats in response to refeeding. Eur J Neurosci 2002; 15: 1013–29PubMedCrossRefGoogle Scholar
  57. 57.
    Cai XJ, Widdowson PS, Harrold J, et al. Hypothalamic orexin expression: modulation by blood glucose and feeding. Diabetes 1999; 48: 2132–7PubMedCrossRefGoogle Scholar
  58. 58.
    Cai XJ, Denis R, Vernon RG, et al. Food restriction selectively increases hypothalamic orexin-B levels in lactating rats. Regul Pept 2001; 97: 163–8PubMedCrossRefGoogle Scholar
  59. 59.
    Yamanaka A, Sakurai T, Katsumoto T, et al. Chronic intracerebroventricular administration of orexin-A to rats increases food intake in daytime, but has no effect on body weight. Brain Res 1999; 849: 248–52PubMedCrossRefGoogle Scholar
  60. 60.
    Sakurai T. Roles of orexins in regulation of feeding and wakefulness. Neuroreport 2002; 13: 987–95PubMedCrossRefGoogle Scholar
  61. 61.
    Sakurai T. Orexin: a link between energy homeostasis and adaptive behaviour. Curr Opin Clin Nutr Metab Care 2003; 6: 353–60PubMedCrossRefGoogle Scholar
  62. 62.
    Vale W, Spiess J, Rivier C, et al. Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science 1981; 213: 1394–7PubMedCrossRefGoogle Scholar
  63. 63.
    Vaughan J, Donaldson C, Bittencourt J, et al. Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor. Nature 1995; 378: 287–92PubMedCrossRefGoogle Scholar
  64. 64.
    Reyes TM, Lewis K, Perrin MH, et al. Urocortin II: a member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors. Proc Natl Acad Sci U S A 2001; 98: 2843–8PubMedCrossRefGoogle Scholar
  65. 65.
    Hsu SY, Hsueh AJW. Human stresscopin and stresscopin-related peptide are selective ligands for the type 2 corticotropin-releasing hormone receptor. Nat Med 2001; 7: 605–11PubMedCrossRefGoogle Scholar
  66. 66.
    Lewis K, Li C, Perrin MH, et al. Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. Proc Natl Acad Sci U S A 2001; 98: 7570–5PubMedCrossRefGoogle Scholar
  67. 67.
    Turnbull AV, Rivier C. Corticotropin-releasing factor (CRF) and endocrine responses to stress: CRF receptors, binding protein, and related peptides. Proc Soc Exp Biol Med 1997; 215: 1–10PubMedGoogle Scholar
  68. 68.
    Brown MR, Fisher LA. Regulation of the autonomic nervous system by corticotropin-releasing factor. In: De Souza EB, Nemeroff CB, editors. Corticotropin-releasing factor: basic and clinical studies of a neuropeptide. Boca Raton (FL): CRC, 1990: 291–8Google Scholar
  69. 69.
    Heinrichs SC, Tache Y. Therapeutic potential of CRF receptor antagonists: a gut-brain perspective. Expert Opin Investig Drugs 2001; 10: 647–59PubMedCrossRefGoogle Scholar
  70. 70.
    Koob GF, Cole BJ, Swerdlow NR, et al. Stress, performance, and arousal: focus on CRF. NIDA Res Monogr 1990; 97: 163–76PubMedGoogle Scholar
  71. 71.
    Krysiak R, Obuchowicz E, Herman ZS. Role of corticotropin-releasing factor (CRF) in anxiety. Pol J Pharmacol 2000; 52: 15–25PubMedGoogle Scholar
  72. 72.
    Spina M, Merlo-Pich E, Chan RKW, et al. Appetite-suppressing effects of urocortin, a CRF-related neuropeptide. Science 1996; 273: 1561–4PubMedCrossRefGoogle Scholar
  73. 73.
    Million M, Saunders P, Rivier J, et al. Compound 338-86-15, a novel peptide CRF-R2 antagonist, selectively blocks CRF and stress-induced delayed gastric emptying in rats [abstract]. Soc Neurosci Abstr 2001; 27: 839.17Google Scholar
  74. 74.
    Krahn DD, Gosnell BA, Levine AS, et al. Behavioral effects of corticotropin-releasing factor: localization and characterization of central effects. Brain Res 1988; 443: 63–9PubMedCrossRefGoogle Scholar
  75. 75.
    Currie PJ, Coscina DV, Bishop C, et al. Hypothalamic paraventricular nucleus injections of urocortin alter food intake and respiratory quotient. Brain Res 2001; 916: 222–8PubMedCrossRefGoogle Scholar
  76. 76.
    Wang C, Mullet MA, Glass MJ, et al. Feeding inhibition by urocortin in the rat ypothalamic paraventricular nucleus. Am J Physiol Regul Integr Comp Physiol 2001; 280: R473–80PubMedGoogle Scholar
  77. 77.
    Bakshi VP, Newman HC, Weinberg LE, et al. Urocortin infusion into lateral septum increases grooming and decreases ingestive behaviors [abstract]. Abstr Soc Neurosci 2001; 27: 414.14Google Scholar
  78. 78.
    Kelly AB, Watts AG. The region of the pontine parabrachial nucleus is a major target of dehydration-sensitive CRH neurons in the rat lateral hypothalamic area. J Comp Neurol 1998; 394: 48–63PubMedCrossRefGoogle Scholar
  79. 79.
    Watts AG, Sanchez-Watts G, Kelly AB. Distinct patterns of neuropeptide gene expression in the lateral hypothalamic area and arcuate nucleus are associated with dehydration-induced anorexia. J Neurosci 1999; 19: 6111–21PubMedGoogle Scholar
  80. 80.
    Egawa M, Yoshimatsu H, Bray GA. Preoptic area injection of corticotropin-releasing hormone stimulates sympathetic activity. Am J Physiol 1990; 259: R799–806PubMedGoogle Scholar
  81. 81.
    Hashimoto K, Makino S, Asaba K, et al. Physiological roles of corticotropin-releasing hormone receptor type 2. Endocr J 2001; 48: 1–9PubMedCrossRefGoogle Scholar
  82. 82.
    Katner JS, Li DL, Grigoriadis DE, et al. Urocortin modulates food consumption and body weight via CRF2a receptor. Abstr Soc Neurosci 2001; 27: 477.10Google Scholar
  83. 83.
    Cullen MJ, Ling N, Foster AC, et al. Urocortin, corticotropin releasing factor-2 receptors and energy balance. Endocrinology 2001; 142: 992–9PubMedCrossRefGoogle Scholar
  84. 84.
    Contarino A, Heinrichs SC, Gold LH. Understanding corticotropin releasing factor neurobiology: contributions from mutant mice. Neuropeptides 1999; 33: 1–12PubMedCrossRefGoogle Scholar
  85. 85.
    Richard D, Rivest R, Naimi N, et al. Expression of corticotropin-releasing factor and its receptors in the brain of lean and obese Zucker rats. Endocrinology 1996; 137: 4786–95PubMedCrossRefGoogle Scholar
  86. 86.
    Makino S, Nishiyama M, Asaba K, et al. Altered expression of type 2 CRH receptor mRNA in the VMH by glucocorticoids and starvation. Am J Physiol Regul Integr Comp Physiol 1998; 44: R1138–45Google Scholar
  87. 87.
    Schwartz MW, Figlewicz DP, Baskin DG, et al. Insulin in the brain: a hormonal regulator of energy balance. Endocr Rev 1992; 13: 387–414PubMedGoogle Scholar
  88. 88.
    Schwartz MW. Biomedicine: staying slim with insulin in mind. Science 2000; 289: 2066–7PubMedCrossRefGoogle Scholar
  89. 89.
    Ahima RS, Flier JS.Leptin. Annu Rev Physiol 2000; 62: 413–37PubMedCrossRefGoogle Scholar
  90. 90.
    Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 1998; 395: 763–70PubMedCrossRefGoogle Scholar
  91. 91.
    Dallman MF, Akana SF, Strack AM, et al. The neural network that regulates energy balance is responsive to glucocorticoids and insulin and also regulates HPA axis responsivity at a site proximal to CRF neurons. Ann N Y Acad Sci 1995; 771: 730–42PubMedCrossRefGoogle Scholar
  92. 92.
    Cabanac M, Richard D. The nature of the ponderostat: Hervey’s hypothesis revived. Appetite 1996; 26: 45–54PubMedCrossRefGoogle Scholar
  93. 93.
    Tschop M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 2000; 407: 908–13PubMedCrossRefGoogle Scholar
  94. 94.
    Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from the stomach. Nature 1999; 402: 656–60PubMedCrossRefGoogle Scholar
  95. 95.
    Nakazato M, Murakami N, Date Y, et al. A role for ghrelin in the central regulation of feeding. Nature 2001; 409: 194–8PubMedCrossRefGoogle Scholar
  96. 96.
    Scherer PE, Williams S, Fogliano M, et al. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 1995; 270: 26746–9PubMedCrossRefGoogle Scholar
  97. 97.
    Banks WA. Leptin transport across the blood-brain barrier: implications for the cause and treatment of obesity. Curr Pharm Des 2001; 7: 125–33PubMedCrossRefGoogle Scholar
  98. 98.
    Banks WA, Kastin AJ, Huang WT, et al. Leptin enters the brain by a saturable system independent of insulin. Peptides 1996; 17: 305–11PubMedCrossRefGoogle Scholar
  99. 99.
    Wilkinson M, Morash B, Ur E. The brain is a source of leptin. Front Horm Res 2000; 26: 106–25PubMedCrossRefGoogle Scholar
  100. 100.
    Schwartz MW, Baskin DG, Bukowski TR, et al. Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice. Diabetes 1996; 45: 531–5PubMedCrossRefGoogle Scholar
  101. 101.
    Kristensen P, Judge ME, Thim L, et al. Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature 1998; 393: 72–6PubMedCrossRefGoogle Scholar
  102. 102.
    Thornton JE, Cheung CC, Clifton DK, et al. Regulation of hypothalamic proopiomelanocortin mRNA by leptin in ob/ob mice. Endocrinology 1997; 138: 5063–6PubMedCrossRefGoogle Scholar
  103. 103.
    Arvaniti K, Huang OL, Richard D. Effects of leptin and corticosterone on the expression of corticotropin-releasing hormone, agouti-related protein, and proopiomelanocortin in the brain of ob/ob mouse. Neuroendocrinology 2001; 73: 227–36PubMedCrossRefGoogle Scholar
  104. 104.
    El-Haschimi K, Pierroz DD, Hileman SM, et al. Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity. J Clin Invest 2000; 105: 1827–32PubMedCrossRefGoogle Scholar
  105. 105.
    Bates SH, Stearns WH, Dundon TA, et al. STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature 2003; 421: 856–9PubMedCrossRefGoogle Scholar
  106. 106.
    Huang Q, Rivest R, Richard D. Effects of leptin on corticotropin-releasing factor (CRF) synthesis and CRF neuron activation in the paraventricular hypothalamic nucleus of obese (ob/ob) mice. Endocrinology 1998; 139: 1524–32PubMedCrossRefGoogle Scholar
  107. 107.
    Heiman ML, Ahima RS, Craft LS, et al. Leptin inhibition of the hypothalamic-pituitary-adrenal axis in response to stress. Endocrinology 1997; 138: 3859–63PubMedCrossRefGoogle Scholar
  108. 108.
    Giovambattista A, Chisari AN, Gaillard RC, et al. Food intake-induced leptin secretion modulates hypothalamo-pituitary-adrenal axis response and hypothalamic Ob-Rb expression to insulin administration. Neuroendocrinology 2000; 72: 341–9PubMedCrossRefGoogle Scholar
  109. 109.
    Lopez M, Seoane L, Garcia MC, et al. Leptin regulation of prepro-orexin and orexin receptor mRNA levels in the hypothalamus. Biochem Biophys Res Commun 2000; 269: 41–5PubMedCrossRefGoogle Scholar
  110. 110.
    Friedman MI, Ramirez I. Food intake in diabetic rats: relationship to metabolic effects of insulin treatment. Physiol Behav 1994; 56: 373–8PubMedCrossRefGoogle Scholar
  111. 111.
    Schwartz MW, Sipols AJ, Marks JL, et al. Inhibition of hypothalamic neuropeptide-Y gene expression by insulin. Endocrinology 1992; 130: 3608–16PubMedCrossRefGoogle Scholar
  112. 112.
    Kotz CM, Briggs JE, Pomonis JD, et al. Neural site of leptin influence on neuropeptide Y signaling pathways altering feeding and uncoupling protein. Am J Physiol Regul Integr Comp Physiol 1998; 44: R478–84Google Scholar
  113. 113.
    Havel PJ, Hahn TM, Sindelar DK, et al. Effects of streptozotocin-induced diabetes and insulin treatment on the hypothalamic melanocortin system and muscle uncoupling protein 3 expression in rats. Diabetes 2000; 49: 244–52PubMedCrossRefGoogle Scholar
  114. 114.
    Bruning JC, Gautam D, Burks DJ, et al. Role of brain insulin receptor in the control of body weight and reproduction. Science 2000; 289: 2122–5PubMedCrossRefGoogle Scholar
  115. 115.
    Makimura H, Mizuno TM, Roberts J, et al. Adrenalectomy reverses obese phenotype and restores hypothalamic melanocortin tone in leptin-deficient ob/ ob mice. Diabetes 2000; 49: 1917–23PubMedCrossRefGoogle Scholar
  116. 116.
    Bray GA, Stern JS, Castonguay TW. Effect of adrenalectomy and high-fat diet on the fatty Zucker rat. Am J Physiol 1992; 262: E32–9PubMedGoogle Scholar
  117. 117.
    Castonguay TW, Dallman MF, Stern JS. Some metabolic and behavioral effects of adrenalectomy on obese Zucker rats. Am J Physiol 1986; 251: R923–33PubMedGoogle Scholar
  118. 118.
    Feldkircher KM, Mistry AM, Romsos DR. Adrenalectomy reverses pre-existing obesity in adult genetically obese (ob/ob) mice. Int J Obes 1996; 20: 232–5Google Scholar
  119. 119.
    Fletcher JM. Effects of adrenalectomy before weaning in the genetically obese. Br J Nutr 1986; 56: 141–51PubMedCrossRefGoogle Scholar
  120. 120.
    Gosselin C, Cabanac M. Adrenalectomy lowers the bodyweight set-point in rats. Physiol Behav 1997; 62: 519–23PubMedCrossRefGoogle Scholar
  121. 121.
    Ouerghi D, Rivest S, Richard D. Adrenalectomy attenuates the effect of chemical castration on energy balance in rats. J Nutr 1992; 122: 369–73PubMedGoogle Scholar
  122. 122.
    Romsos DR. Interactions between diet composition and adrenal secretions in energy balance in ob/ob mice. In: Romsos D, editor. Obesity: dietary factors and control. Basel: S. Karger, 1991: 39–44Google Scholar
  123. 123.
    York DA, Godbole V. Effect of adrenalectomy on obese ‘fatty’ rats. Horm Metab Res 1979; 11: 646PubMedCrossRefGoogle Scholar
  124. 124.
    Solomon J, Mayer J. The effect of adrenalectomy on the development of the obese-hyperglycemic syndrome in ob/ob mice. Endocrinology 1973; 93: 510–3PubMedCrossRefGoogle Scholar
  125. 125.
    Deshaies Y, Dagnault A, Lalonde J, et al. Interaction of corticosterone and gonadal steroids on lipid deposition in the female rat. Am J Physiol 1997; 36: E355–62Google Scholar
  126. 126.
    Bjorntorp P, Holm G, Rosmond R. Hypothalamic arousal, insulin resistance and type 2 diabetes mellitus. Diabet Med 1999; 16: 373–83PubMedCrossRefGoogle Scholar
  127. 127.
    Andrews RC, Walker BR. Glucocorticoids and insulin resistance: old hormones, new targets. Clin Sci 1999; 96: 513–23PubMedCrossRefGoogle Scholar
  128. 128.
    Funder JW. Corticosteroid receptors in the brain. In: Motta M, editor. Brain endocrinology. NewYork (NY): Raven, 1991: 133–51Google Scholar
  129. 129.
    De Kloet ER. Brain corticosteroid receptor balance and homeostatic control. Front Neuroendocrinol 1991; 12: 95–164Google Scholar
  130. 130.
    Funder JW. Glucocorticoid receptors. J Steroid Biochem Mol Biol 1992; 43: 389–94PubMedCrossRefGoogle Scholar
  131. 131.
    Devenport L, Knehans A, Sundstrom A, et al. Corticosterone’s dual metabolic actions. Life Sci 1989; 45: 1389–96Google Scholar
  132. 132.
    Ur E, Grossman A, Despres JP. Obesity results as a consequence of glucocorticoid induced leptin resistance. Horm Metab Res 1996; 28: 744–7PubMedCrossRefGoogle Scholar
  133. 133.
    Arvaniti K, Deshaies Y, Richard D. Effect of leptin on energy balance does not require the presence of intact adrenals. Am J Physiol 1998; 275: R105–11PubMedGoogle Scholar
  134. 134.
    Bluher M, Windgassen M, Paschke R. Improvement of insulin sensitivity after adrenalectomy in patients with pheochromocytoma. Diabetes Care 2000; 23: 1591–2PubMedCrossRefGoogle Scholar
  135. 135.
    Chavez M, Seeley RJ, Green PK, et al. Adrenalectomy increases sensitivity to central insulin. Physiol Behav 1997; 62: 631–4PubMedCrossRefGoogle Scholar
  136. 136.
    Tschop M, Flora DB, Mayer JP, et al. Hypophysectomy prevents ghrelin-induced adiposity and increases gastric ghrelin secretion in rats. Obes Res 2002; 10: 991–9PubMedCrossRefGoogle Scholar
  137. 137.
    Akana SF, Strack AM, Hanson ES, et al. Regulation of activity in the hypothalamo-pituitary-adrenal axis is integral to a larger hypothalamic system that determines caloric flow. Endocrinology 1994; 135: 1125–34PubMedCrossRefGoogle Scholar
  138. 138.
    Kiss A, Jezova D, Aguilera G. Activity of the hypothalamic-pituitary-adrenal axis and sympathoadrenal system during food and water deprivation in the rat. Brain Res 1994; 663: 84–92PubMedCrossRefGoogle Scholar
  139. 139.
    Woodward CJH, Hervey GR, Oakey RE, et al. The effects of fasting on plasma corticosterone kinetics in rats. Br J Nutr 1991; 66: 117–27PubMedCrossRefGoogle Scholar
  140. 140.
    Sawchenko PE, Li HY, Ericsson A. Circuits and mechanisms governing hypothalamic responses to stress: a tale of two paradigms. Prog Brain Res 2000; 122: 61–78PubMedCrossRefGoogle Scholar
  141. 141.
    Herman JP, Cullinan WE. Neurocircuitry of stress: central control of the hypothalamo-pituitary-adrenocortical axis. Trends Neurosci 1997; 20: 78–84PubMedCrossRefGoogle Scholar
  142. 142.
    Ishizuka B, Quigley ME, Yen SS. Pituitary hormone release in response to food ingestion: evidence for neuroendocrine signals from gut to brain. J Clin Endocrinol Metab 1983; 57: 1111–6PubMedCrossRefGoogle Scholar
  143. 143.
    Honma K, Honma S, Hirai T, et al. Food ingestion is more important to plasma corticosterone dynamics than water intake in rats under restricted daily feeding. Physiol Behav 1986; 37: 791–5PubMedCrossRefGoogle Scholar
  144. 144.
    Boivin A, Deshaies Y. Contribution of hyperinsulinemia to modulation of lipoprotein lipase activity in the obese Zucker rat. Metabolism 2000; 49: 134–40PubMedCrossRefGoogle Scholar
  145. 145.
    Boivin A, Deshaies Y. Dietary rat models in which the development of hypertriglyceridemia and that of insulin resistance are dissociated. Metabolism 1995; 44: 1540–7PubMedCrossRefGoogle Scholar
  146. 146.
    Drucker DJ. Minireview: the glucagon-like peptides. Endocrinology 2001; 142: 521–7PubMedCrossRefGoogle Scholar
  147. 147.
    Han VK, Hynes MA, Jin C, et al. Cellular localization of proglucagon/glucagonlike peptide I messenger RNAs in rat brain. J Neurosci Res 1986; 16: 97–107PubMedCrossRefGoogle Scholar
  148. 148.
    Goldstone AP, Morgan I, Mercer JG, et al. Effect of leptin on hypothalamic GLP-1 peptide and brain-stem pre-proglucagon mRNA. Biochem Biophys Res Commun 2000; 269: 331–5PubMedCrossRefGoogle Scholar
  149. 149.
    Larsen PJ, Tang-Christensen M, Jessop DS. Central administration of glucagonlike peptide-1 activates hypothalamic neuroendocrine neurons in the rat. Endocrinology 1997; 138: 4445–55PubMedCrossRefGoogle Scholar
  150. 150.
    Imeryuz N, Yegen BC, Bozkurt A, et al. Glucagon-like peptide-1 inhibits gastric emptying via vagal afferent-mediated central mechanisms. Am J Physiol 1997; 273: G920–7PubMedGoogle Scholar
  151. 151.
    MacLusky NJ, Cook S, Scrocchi L, et al. Neuroendocrine function and response to stress in mice with complete disruption of glucagon-like peptide-1 receptor signaling. Endocrinology 2000; 141: 752–62PubMedCrossRefGoogle Scholar
  152. 152.
    Hayashida T, Murakami K, Mogi K, et al. Ghrelin in domestic animals: distribution in stomach and its possible role. Domest Anim Endocrinol 2001; 21: 17–24PubMedCrossRefGoogle Scholar
  153. 153.
    Toshinai K, Mondal MS, Nakazato M, et al. Upregulation of ghrelin expression in the stomach upon fasting, insulin-induced hypoglycemia, and leptin administration. Biochem Biophys Res Commun 2001; 281: 1220–5PubMedCrossRefGoogle Scholar
  154. 154.
    Tschop M, Wawarta R, Riepl RL, et al. Post-prandial decrease of circulating human ghrelin levels. J Endocrinol Invest 2001; 24: RC19–21PubMedGoogle Scholar
  155. 155.
    Asakawa A, Inui A, Kaga T, et al. A role of ghrelin in neuroendocrine and behavioral responses to stress in mice. Neuroendocrinology 2001; 74: 143–7PubMedCrossRefGoogle Scholar
  156. 156.
    Arvat E, Maccario M, Di Vito L, et al. Endocrine activities of ghrelin, a natural growth hormone secretagogue (GHS), in humans: comparison and interactions with hexarelin, a nonnatural peptidyl GHS, and GH-releasing hormone. J Clin Endocrinol Metab 2001; 86: 1169–74PubMedCrossRefGoogle Scholar
  157. 157.
    Gura T. Obesity drug pipeline not so fat. Science 2003; 299: 849–52PubMedCrossRefGoogle Scholar
  158. 158.
    Preti A. Axokine (Regeneron). Drugs 2003; 6: 696–701Google Scholar
  159. 159.
    Marsh DJ, Hollopeter G, Huszar D, et al. Response of melanocortin-4 receptor-deficient mice to anorectic and orexigenic peptides. Nat Genet 1999; 21: 119–22PubMedCrossRefGoogle Scholar
  160. 160.
    Hildebrandt AL, Kelly-Sullivan DM, Black SC. Antiobesity effects of chronic cannabinoid CB1 receptor antagonist treatment in diet-induced obese mice. Eur J Pharmacol 2003; 462: 125–32PubMedCrossRefGoogle Scholar
  161. 161.
    Ravinet Trillou C, Arnone M, Delgorge C, et al. Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice. Am J Physiol Regul Integr Comp Physiol 2003; 284: R345–53Google Scholar
  162. 162.
    Bray GA, Hollander P, Klein S, et al. A 6-month randomized, placebo-controlled, dose-ranging trial of topiramate for weight loss in obesity. Obes Res 2003; 11: 722–33PubMedCrossRefGoogle Scholar
  163. 163.
    Richard D, Ferland J, Lalonde J, et al. Influence of topiramate in the regulation of energy balance. Nutrition 2000; 16: 961–6PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.D.B. Brown Obesity Research Chair and Centre de recherche de l’Hôpital LavalInstitut universitaire de cardiologie et de pneumologie QuébecQuébecCanada
  2. 2.Department of Anatomy and Physiology, Faculty of MedicineLaval UniversityQuébecCanada

Personalised recommendations