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.
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References
Kopelman PG. Obesity as a medical problem. Nature 2000; 404: 635–43
Despres JP. Drug treatment for obesity: we need more studies in men at higher risk of coronary events. BMJ 2001; 322: 1379–80
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: R183–91
Galpin KS, Henderson RG, James WPT, et al. GDP binding to brown-adiposetissue mitochondria of mice treated chronically with corticosterone. Biochem J 1983; 214: 265–8
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: 4000–4
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: R142–9
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: 521–5
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: 1492–6
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: 327–40
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: E287–95
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: 1873–9
Tsai HJ, Romsos DR. Glucocorticoid and mineralocorticoid receptor-binding characteristics in obese (ob/ob) mice. Am J Physiol 1991; 261: E495–9
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: 765–71
White BD, Corll CB, Porter JR. The metabolic clearance rate of corticosterone in lean and obese male Zucker rats. Metabolism 1989; 38: 530–6
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: 708–11
Bjorntorp P, Rosmond R. Obesity and cortisol. Nutrition 2000; 16: 924–36
Schwartz MW, Woods SC, Porte Jr D, et al. Central nervous system control of food intake. Nature 2000; 404: 661–71
Elmquist JK. Anatomic basis of leptin action in the hypothalamus. Front Horm Res 2000; 26: 21–41
Cone RD. The central melanocortin system and energy homeostasis. Trends Endocrinol Metab 1999; 10: 211–6
Richard D. The role of CRF in the regulation of energy balance. Curr Opin Endocrinol Diabetes 1999; 6: 10–8
Sleeman MW, Anderson KD, Lambert PD, et al. The ciliary neurotrophic factor and its receptor, CNTFR alpha. Pharm Acta Helv 2000; 74: 265–72
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: 385–96
Woods SC, Schwartz MW, Baskin DG, et al. Food intake and the regulation of body weight. Annu Rev Psychol 2000; 51: 255–77
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: 186–94
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: 794–801
Hanson ES, Dallman MF. Neuropeptide y (NPY) may integrate responses of hypothalamic feeding systems and the hypothalamo-pituitary-adrenal axis. J Neuroendocrinol 1995; 7: 273–9
Kuru M, Ueta Y, Serino R, et al. Centrally administered orexin/hypocretin activates HPA axis in rats. Neuroreport 2000; 11: 1977–80
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: 297–303
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: 303–10
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: 110–2
Papadopoulos AD, Wardlaw SL. Endogenous alpha-MSH modulates the hypothalamic-pituitary-adrenal response to the cytokine interleukin-1beta. J Neuroendocrinol 1999; 11: 315–9
Mountjoy KG, Wong J. Obesity, diabetes and functions for proopiomelanocortinderived peptides. Mol Cell Endocrinol 1997; 128: 171–7
Wikberg JES. Melanocortin receptors: new opportunities in drug discovery. Expert Opin Ther Patents 2001; 11: 61–76
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: 97–102
Huszar D, Lynch CA, Fairchild-Huntress V, et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 1997; 88: 131–41
Lu D, Willard D, Patel IR, et al. Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor. Nature 1994; 371: 799–802
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: 1050–6
Hahn TM, Breininger JF, Baskin DG, et al. Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons. Nat Neurosci 1998; 1: 271–2
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: 593–602
Mizuno TM, Mobbs CV. Hypothalamic agouti-related protein messenger ribonucleic acid is inhibited by leptin and stimulated by fasting. Endocrinology 1999; 140: 814–7
DiMarzo V, Goparaju SK, Wang L, et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 2001; 410: 822–5
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: 377–80
Pertwee RG. Pharmacology of cannabinoid receptor ligands. Curr Med Chem 1999; 6: 635–64
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: 12–9
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: 173–9
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: 724–8
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: 147–56
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: 4850–7
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: 573–85
de Lecea L, Kilduff TS, Peyron C, et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 1998; 95: 322–7
Chemelli RM, Willie JT, Sinton CM, et al. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 1999; 98: 437–51
Peyron C, Tighe DK, van den Pol AN, et al. Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 1998; 18: 9996–10015
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: 1455–70
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: 6–25
Sweet DC, Levine AS, Billington CJ, et al. Feeding response to central orexins. Brain Res 1999; 821: 535–8
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: 1013–29
Cai XJ, Widdowson PS, Harrold J, et al. Hypothalamic orexin expression: modulation by blood glucose and feeding. Diabetes 1999; 48: 2132–7
Cai XJ, Denis R, Vernon RG, et al. Food restriction selectively increases hypothalamic orexin-B levels in lactating rats. Regul Pept 2001; 97: 163–8
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: 248–52
Sakurai T. Roles of orexins in regulation of feeding and wakefulness. Neuroreport 2002; 13: 987–95
Sakurai T. Orexin: a link between energy homeostasis and adaptive behaviour. Curr Opin Clin Nutr Metab Care 2003; 6: 353–60
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: 1394–7
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: 287–92
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: 2843–8
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: 605–11
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: 7570–5
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: 1–10
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: 291–8
Heinrichs SC, Tache Y. Therapeutic potential of CRF receptor antagonists: a gut-brain perspective. Expert Opin Investig Drugs 2001; 10: 647–59
Koob GF, Cole BJ, Swerdlow NR, et al. Stress, performance, and arousal: focus on CRF. NIDA Res Monogr 1990; 97: 163–76
Krysiak R, Obuchowicz E, Herman ZS. Role of corticotropin-releasing factor (CRF) in anxiety. Pol J Pharmacol 2000; 52: 15–25
Spina M, Merlo-Pich E, Chan RKW, et al. Appetite-suppressing effects of urocortin, a CRF-related neuropeptide. Science 1996; 273: 1561–4
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: 839.17
Krahn DD, Gosnell BA, Levine AS, et al. Behavioral effects of corticotropin-releasing factor: localization and characterization of central effects. Brain Res 1988; 443: 63–9
Currie PJ, Coscina DV, Bishop C, et al. Hypothalamic paraventricular nucleus injections of urocortin alter food intake and respiratory quotient. Brain Res 2001; 916: 222–8
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: R473–80
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: 414.14
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: 48–63
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: 6111–21
Egawa M, Yoshimatsu H, Bray GA. Preoptic area injection of corticotropin-releasing hormone stimulates sympathetic activity. Am J Physiol 1990; 259: R799–806
Hashimoto K, Makino S, Asaba K, et al. Physiological roles of corticotropin-releasing hormone receptor type 2. Endocr J 2001; 48: 1–9
Katner JS, Li DL, Grigoriadis DE, et al. Urocortin modulates food consumption and body weight via CRF2a receptor. Abstr Soc Neurosci 2001; 27: 477.10
Cullen MJ, Ling N, Foster AC, et al. Urocortin, corticotropin releasing factor-2 receptors and energy balance. Endocrinology 2001; 142: 992–9
Contarino A, Heinrichs SC, Gold LH. Understanding corticotropin releasing factor neurobiology: contributions from mutant mice. Neuropeptides 1999; 33: 1–12
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: 4786–95
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: R1138–45
Schwartz MW, Figlewicz DP, Baskin DG, et al. Insulin in the brain: a hormonal regulator of energy balance. Endocr Rev 1992; 13: 387–414
Schwartz MW. Biomedicine: staying slim with insulin in mind. Science 2000; 289: 2066–7
Ahima RS, Flier JS.Leptin. Annu Rev Physiol 2000; 62: 413–37
Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 1998; 395: 763–70
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: 730–42
Cabanac M, Richard D. The nature of the ponderostat: Hervey’s hypothesis revived. Appetite 1996; 26: 45–54
Tschop M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 2000; 407: 908–13
Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from the stomach. Nature 1999; 402: 656–60
Nakazato M, Murakami N, Date Y, et al. A role for ghrelin in the central regulation of feeding. Nature 2001; 409: 194–8
Scherer PE, Williams S, Fogliano M, et al. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 1995; 270: 26746–9
Banks WA. Leptin transport across the blood-brain barrier: implications for the cause and treatment of obesity. Curr Pharm Des 2001; 7: 125–33
Banks WA, Kastin AJ, Huang WT, et al. Leptin enters the brain by a saturable system independent of insulin. Peptides 1996; 17: 305–11
Wilkinson M, Morash B, Ur E. The brain is a source of leptin. Front Horm Res 2000; 26: 106–25
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: 531–5
Kristensen P, Judge ME, Thim L, et al. Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature 1998; 393: 72–6
Thornton JE, Cheung CC, Clifton DK, et al. Regulation of hypothalamic proopiomelanocortin mRNA by leptin in ob/ob mice. Endocrinology 1997; 138: 5063–6
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: 227–36
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: 1827–32
Bates SH, Stearns WH, Dundon TA, et al. STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature 2003; 421: 856–9
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: 1524–32
Heiman ML, Ahima RS, Craft LS, et al. Leptin inhibition of the hypothalamic-pituitary-adrenal axis in response to stress. Endocrinology 1997; 138: 3859–63
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: 341–9
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: 41–5
Friedman MI, Ramirez I. Food intake in diabetic rats: relationship to metabolic effects of insulin treatment. Physiol Behav 1994; 56: 373–8
Schwartz MW, Sipols AJ, Marks JL, et al. Inhibition of hypothalamic neuropeptide-Y gene expression by insulin. Endocrinology 1992; 130: 3608–16
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: R478–84
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: 244–52
Bruning JC, Gautam D, Burks DJ, et al. Role of brain insulin receptor in the control of body weight and reproduction. Science 2000; 289: 2122–5
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: 1917–23
Bray GA, Stern JS, Castonguay TW. Effect of adrenalectomy and high-fat diet on the fatty Zucker rat. Am J Physiol 1992; 262: E32–9
Castonguay TW, Dallman MF, Stern JS. Some metabolic and behavioral effects of adrenalectomy on obese Zucker rats. Am J Physiol 1986; 251: R923–33
Feldkircher KM, Mistry AM, Romsos DR. Adrenalectomy reverses pre-existing obesity in adult genetically obese (ob/ob) mice. Int J Obes 1996; 20: 232–5
Fletcher JM. Effects of adrenalectomy before weaning in the genetically obese. Br J Nutr 1986; 56: 141–51
Gosselin C, Cabanac M. Adrenalectomy lowers the bodyweight set-point in rats. Physiol Behav 1997; 62: 519–23
Ouerghi D, Rivest S, Richard D. Adrenalectomy attenuates the effect of chemical castration on energy balance in rats. J Nutr 1992; 122: 369–73
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: 39–44
York DA, Godbole V. Effect of adrenalectomy on obese ‘fatty’ rats. Horm Metab Res 1979; 11: 646
Solomon J, Mayer J. The effect of adrenalectomy on the development of the obese-hyperglycemic syndrome in ob/ob mice. Endocrinology 1973; 93: 510–3
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: E355–62
Bjorntorp P, Holm G, Rosmond R. Hypothalamic arousal, insulin resistance and type 2 diabetes mellitus. Diabet Med 1999; 16: 373–83
Andrews RC, Walker BR. Glucocorticoids and insulin resistance: old hormones, new targets. Clin Sci 1999; 96: 513–23
Funder JW. Corticosteroid receptors in the brain. In: Motta M, editor. Brain endocrinology. NewYork (NY): Raven, 1991: 133–51
De Kloet ER. Brain corticosteroid receptor balance and homeostatic control. Front Neuroendocrinol 1991; 12: 95–164
Funder JW. Glucocorticoid receptors. J Steroid Biochem Mol Biol 1992; 43: 389–94
Devenport L, Knehans A, Sundstrom A, et al. Corticosterone’s dual metabolic actions. Life Sci 1989; 45: 1389–96
Ur E, Grossman A, Despres JP. Obesity results as a consequence of glucocorticoid induced leptin resistance. Horm Metab Res 1996; 28: 744–7
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: R105–11
Bluher M, Windgassen M, Paschke R. Improvement of insulin sensitivity after adrenalectomy in patients with pheochromocytoma. Diabetes Care 2000; 23: 1591–2
Chavez M, Seeley RJ, Green PK, et al. Adrenalectomy increases sensitivity to central insulin. Physiol Behav 1997; 62: 631–4
Tschop M, Flora DB, Mayer JP, et al. Hypophysectomy prevents ghrelin-induced adiposity and increases gastric ghrelin secretion in rats. Obes Res 2002; 10: 991–9
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: 1125–34
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: 84–92
Woodward CJH, Hervey GR, Oakey RE, et al. The effects of fasting on plasma corticosterone kinetics in rats. Br J Nutr 1991; 66: 117–27
Sawchenko PE, Li HY, Ericsson A. Circuits and mechanisms governing hypothalamic responses to stress: a tale of two paradigms. Prog Brain Res 2000; 122: 61–78
Herman JP, Cullinan WE. Neurocircuitry of stress: central control of the hypothalamo-pituitary-adrenocortical axis. Trends Neurosci 1997; 20: 78–84
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: 1111–6
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: 791–5
Boivin A, Deshaies Y. Contribution of hyperinsulinemia to modulation of lipoprotein lipase activity in the obese Zucker rat. Metabolism 2000; 49: 134–40
Boivin A, Deshaies Y. Dietary rat models in which the development of hypertriglyceridemia and that of insulin resistance are dissociated. Metabolism 1995; 44: 1540–7
Drucker DJ. Minireview: the glucagon-like peptides. Endocrinology 2001; 142: 521–7
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: 97–107
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: 331–5
Larsen PJ, Tang-Christensen M, Jessop DS. Central administration of glucagonlike peptide-1 activates hypothalamic neuroendocrine neurons in the rat. Endocrinology 1997; 138: 4445–55
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: G920–7
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: 752–62
Hayashida T, Murakami K, Mogi K, et al. Ghrelin in domestic animals: distribution in stomach and its possible role. Domest Anim Endocrinol 2001; 21: 17–24
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: 1220–5
Tschop M, Wawarta R, Riepl RL, et al. Post-prandial decrease of circulating human ghrelin levels. J Endocrinol Invest 2001; 24: RC19–21
Asakawa A, Inui A, Kaga T, et al. A role of ghrelin in neuroendocrine and behavioral responses to stress in mice. Neuroendocrinology 2001; 74: 143–7
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: 1169–74
Gura T. Obesity drug pipeline not so fat. Science 2003; 299: 849–52
Preti A. Axokine (Regeneron). Drugs 2003; 6: 696–701
Marsh DJ, Hollopeter G, Huszar D, et al. Response of melanocortin-4 receptor-deficient mice to anorectic and orexigenic peptides. Nat Genet 1999; 21: 119–22
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: 125–32
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: R345–53
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: 722–33
Richard D, Ferland J, Lalonde J, et al. Influence of topiramate in the regulation of energy balance. Nutrition 2000; 16: 961–6
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Richard, D., Baraboi, D. Circuitries Involved in the Control of Energy Homeostasis and the Hypothalamic-Pituitary-Adrenal Axis Activity. Mol Diag Ther 3, 269–277 (2004). https://doi.org/10.2165/00024677-200403050-00001
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DOI: https://doi.org/10.2165/00024677-200403050-00001