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The hypothalamus and the regulation of energy homeostasis: lifting the lid on a black box

  • Gareth Williams (a1), Joanne A. Harrold (a1) and David J. Cutler (a1)


The hypothalamus is the focus of many peripheral signals and neural pathways that control energy homeostasis and body weight. Emphasis has moved away from anatomical concepts of ‘feeding’ and ‘satiety’ centres to the specific neurotransmitters that modulate feeding behaviour and energy expenditure. We have chosen three examples to illustrate the physiological roles of hypothalamic neurotransmitters and their potential as targets for the development of new drugs to treat obesity and other nutritional disorders. Neuropeptide Y (NPY) is expressed by neurones of the hypothalamic arcuate nucleus (ARC) that project to important appetite-regulating nuclei, including the paraventricular nucleus (PVN). NPY injected into the PVN is the most potent central appetite stimulant known, and also inhibits thermogenesis; repeated administration rapidly induces obesity. The ARC NPY neurones are stimulated by starvation, probably mediated by falls in circulating leptin and insulin (which both inhibit these neurones), and contribute to the increased hunger in this and other conditions of energy deficit. They therefore act homeostatically to correct negative energy balance. ARC NPY neurones also mediate hyperphagia and obesity in the ob/ob and db/db mice and fa/fa rat, in which leptin inhibition is lost through mutations affecting leptin or its receptor. Antagonists of the Y5 receptor (currently thought to be the NPY ‘feeding’ receptor) have anti-obesity effects. Melanocortin-4 receptors (MC4-R) are expressed in various hypothalamic regions, including the ventromedial nucleus and ARC. Activation of MC4-R by agonists such as α-melanocyte-stimulating hormone (a cleavage product of pro-opiomelanocortin which is expressed in ARC neurones) inhibits feeding and causes weight loss. Conversely, MC4-R antagonists such as ‘agouti’ protein and agouti gene-related peptide (AGRP) stimulate feeding and cause obesity. Ectopic expression of agouti in the hypothalamus leads to obesity in the AVY mouse, while AGRP is co-expressed by NPY neurones in the ARC. Synthetic MC4-R agonists may ultimately find use as anti-obesity drugs in human subjects Orexins-A and -B, derived from prepro-orexin, are expressed in specific neurones of the lateral hypothalamic area (LHA). Orexin-A injected centrally stimulates eating and prepro-orexin mRNA is up regulated by fasting and hypoglycaemia. The LHA is important in receiving sensory signals from the gut and liver, and in sensing glucose, and orexin neurones may be involved in stimulating feeding in response to falls in plasma glucose.

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Corresponding author

*Corresponding author: Professor Gareth Williams, fax +44 (0)151 706 5797, email


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Banks, WA, Kastin, AJ, Huang, W, Jaspan, JB & Maness, LM (1996) Leptin enters the brain by a saturable system independent of insulin. Peptides 17, 305311.
Baskin, DG, Breininger, JF & Schwartz, MW (1999) Leptin receptor mRNA identifies a subpopulation of neuropeptide Y neurons activated by fasting in rat hypothalamus. Diabetes 48, 828833.
Beck, B & Richy, S (1999) Hypothalamic hypocretin/orexin and neuropeptide Y: Divergent interaction with energy depletion and leptin. Biochemical and Biophysical Research Communications 258, 119122.
Bernardis, LL & Bellinger, LL (1996) The lateral hypothalamic area revisited: Ingestion behavior. Neuroscience and Biobehavior Reviews 20, 189287.
Boston, BA, Blaydon, KM, Varnerin, J & Cone, RD (1997) Independent and additive effects of central POMC and leptin pathways on murine obesity. Science 278, 16411644.
Broberger, C, de Lecea, L, Sutcliffe, JG & Hökfelt, T (1998a) Hypocretin/orexin- and melanin-concentrating hormone-expressing cells form distinct populations in the rodent lateral hypothalamus: Relationship to the neuropeptide Y and agouti gene-related protein systems. Journal of Comparative Neurology 402, 460474.
Broberger, C, Johansen, J, Johansson, C, Schalling, M & Hökfelt, T (1998b) The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice. Proceedings of the National Academy of Sciences USA 95, 1504315048.
Cai, X, Widdowson, PS, Harrold, J, Wilson, S, Buckingham, R, Arch, JRS, Tadayyon, M, Clapham, JC, Wilding, J & Williams, G (1999) Hypothalamic orexin expression: Modulation by blood glucose and feeding. Diabetes 48, 21322137.
Chemelli, RM, Willie, JT, Sinton, CM, Elmquist, JK, Scammell, T, Lee, C, Richardson, JA, Williams, SC, Xiong, Y, Kisanuki, Y, Fitch, TE, Nakazato, M, Hammer, RE, Saper, CB & Yanagisawa, M (1999) Narcolepsy in orexin knockout mice: Molecular genetics of sleep regulation. Cell 98, 437451.
Chen, C-T, Dun, SL, Kwok, EH, Dun, NJ & Chang, J-K (1999) Orexin A-like immunoreactivity in the rat brain. Neuroscience Letters 260, 161164.
Cheung, CC, Clifton, DK & Steiner, RA (1997) Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus. Endocrinology 138, 44894492.
Chronwall, BM (1985) Anatomy and physiology of the neuroendocrine arcuate nucleus. Peptides 6, 111.
Criscione, L, Rigollier, P, Batzl-Hartmann, C, Rueger, H, Stricker-Krongrad, A, Wyss, P, Brunner, L, Whitebread, S, Yamaguchi, Y, Gerald, C, Heurich, RO, Walker, MW, Chiesi, M, Schilling, W, Hofbauer, KG & Levens, N (1998) Food intake in free-feeding and energy-deprived lean rats is mediated by the neuropeptide Y5 receptor. Journal of Clinical Investigation 102, 21362145.
Csiffary, A, Gorcs, TJ & Palkovits, M (1990) Neuropeptide Y innervation of ACTH-immunoreactive neurons in the ARC of rats: A correlated light and electron microscopic double immunolabeling study. Brain Research 506, 215222.
Cutler, DJ, Morris, R, Sheridhar, V, Wattam, TAK, Holmes, S, Patel, S, Arch, JRS, Wilson, S, Buckingham, RE, Evans, ML, Leslie, RA & Williams, G (1999) Differential distribution of orexin-A and orexin-B immunoreactivity in the rat brain and spinal cord. Peptides 20, 14551470.
Dagerlind, A, Friberg, K, Bean, A & Hokfelt, T (1992) Sensitive mRNA detection using unfixed tissue: Combined radioactive and non-radioactive in situ hybrid histochemistry. Histochemistry 98, 3949.
Date, Y, Ueta, Y, Yamashita, H, Yamaguchi, H, Matsukura, S, Kangawa, K, Sakurai, T, Yanagisawa, M & Nakazato, M (1999) Orexins, orexigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systems. Proceedings of the National Academy of Sciences USA 96, 748753.
de Lecea, L, Kilduff, TS, Peyron, C, Gao, X-B, Foye, PE, Danielson, PE, Fukuhara, C, Battenberg, ELF, Gautvik, VT, Bartlett, FS, Frankel, WN, van den Pol, AN, Bloom, FE, Gautvik, KM & Sutcliffe, JG (1998) The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity. Proceedings of the National Academy of Sciences USA 95, 322327.
Dryden, S, Frankish, H, Wang, Q & Williams, G (1994) Neuropeptide Y and energy balance: One way ahead for the treatment of obesity. European Journal of Clinical Investigation 24, 293308.
Dryden, S, King, P, Pickavance, L, Doyle, P & Williams, G (1999) Divergent effects of intracerebroventricular and peripheral leptin administration on feeding and hypothalamic neuropeptide Y in lean and obese (fa/fa) Zucker rats. Clinical Science 96, 307312.
Dryden, S, King, P & Williams, G (2000) Neuropeptide Y and the regulation of energy homeostasis. Behavioral and Neuropsychological Review (In the Press).
Dyer, CJ, Touchette, KJ, Carroll, JA, Allee, GL & Matteri, RL (1999) Cloning of porcine prepro-orexin cDNA and effects of an intramuscular injection of synthetic porcine orexin-B on feed intake in young pigs. Domestic Animal Endocrinology 16, 145148.
Edwards, CMB, Abusnana, S, Sunter, D, Murphy, KG, Ghatei, MA & Bloom, SR (1999) The effect of the orexins on food intake: Comparison with neuropeptide Y, melanin-concentrating hormone and galanin. Journal of Endocrinology 160, R7-R12.
Egawa, M, Yoshimatsu, H & Bray, GA (1991) Neuropeptide Y suppresses sympathetic activity to interscapular brown adipose tissue. American Journal of Physiology 260, R328-R334.
Elias, CF, Saper, CB, Maratos-Flier, E, Tritos, NA, Lee, C, Kelly, J, Tatro, JB, Hoffman, GE, Ollmann, MM, Barsh, GS, Sakurai, T, Yanagisawa, M & Elmquist, JK (1998) Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area. Journal of Comparative Neurology 402, 442459.
Elmquist, JK, Ahima, RS, Elias, CF, Flier, JS & Saper, CB (1998) Leptin activates distinct projections from the dorsomedial and ventromedial hypothalamic nuclei. Proceedings of the National Academy of Sciences USA 95, 741746.
Erickson, JC, Clegg, KE & Palmiter, RD (1996a) Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y. Nature 381, 415421.
Erickson, JC, Hollopeter, G & Palmiter, RD (1996b) Attenuation of the obesity syndrome of ob/ob mice by the loss of neuropeptide Y. Science 274, 17041707.
Fan, W, Boston, BA, Kesterson, RA, Hruby, VJ & Cone, RD (1997) Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature 385, 165168.
Flynn, MC, Plata-Salaman, CR & Ffench-Mullen, JM (1999) Neuropeptide Y-related compounds and feeding. Physiology and Behavior 65, 901905.
Friedman, JM & Halaas, JL (1998) Leptin and the regulation of body weight in mammals. Nature 395, 763770.
Fuxe, K, Tinner, B, Caberlotto, L, Bunnemann, B & Agnati, LF (1997) NPY Y1 receptor like immunoreactivity exists in a subpopulation of beta-endorphin immunoreactive nerve cells in the arcuate nucleus: A double immunolabelling analysis in the rat. Neuroscience Letters 225, 4952.
Gerald, C, Walker, MW, Criscione, L, Gustafson, EL, Batzl-Hartmann, C, Smith, KE, Vaysse, P, Durkin, MM, Laz, TM, Linemeyer, DL, Schaffhauser, AO, Whiteshank, S, Hofbauer, KG, Taber, RI, Branchek, TA & Weinshank, RL (1996) A receptor subtype involved in neuropeptide Y-induced food intake. Nature 382, 168171.
Griffond, B, Risold, PY, Jacquemard, C, Colard, C & Fellmann, D (1999) Insulin-induced hypoglycemia increases preprohypocretin (orexin) mRNA in the rat lateral hypothalamic area. Neuroscience Letters 262, 7780.
Guan, XM, Yu, H, Trumbauer, M, Frazier, E, Van der Ploeg, LH & Chen, H (1998) Induction of neuropeptide Y expression in dorso-medial hypothalamus of diet-induced obese mice. NeuroReport 9, 34153419.
Håkansson, M, de Lecea, L, Sutcliffe, JG, Yanagisawa, M & Meister, B (1999) Leptin receptor and STAT3-immunoreactivities in hypocretin/orexin neurones of the lateral hypothalamus. Journal of Neuroendocrinology 11, 653663.
Halaas, JL, Boozer, C, Blair-West, J, Fidhausein, N, Denton, DA & Friedman, JM (1997) Physiological responses to long-term peripheral and central leptin infusion in lean and obese mice. Proceedings of the National Academy of Sciences USA 94, 88788883.
Harrold, JA, Widdowson, PS & Williams, G (1999a) Altered energy balance causes selective changes in melanocortin-4 (MC4-R) but not melanocortin-3 (MC3-R) receptors in specific hypothalamic regions: Further evidence that MC4-R activation is a physiological inhibitor of feeding. Diabetes 48, 267271.
Harrold, JA, Widdowson, PS & Williams, G (1999b) Changes in hypothalamic agouti-related peptide (AGRP), but not a-MSH or pro-opiomelanocortin concentrations in dietary-obese and food-restricted rats. Biochemical and Biophysical Research Communications 258, 574577.
Haskell-Luevano, C, Chen, P, Li, C, Chang, K, Smith, MS, Cameron, JL & Cone, RD (1999) Characterization of the neuroanatomical distribution of agouti-related protein immunoreactivity in the rhesus monkey and the rat. Endocrinology 140, 14081415.
Haynes, AC, Jackson, B, Overend, P, Buckingham, RE, Wilson, S, Tadayyon, M & Arch, JRS (1999) Effects of single and chronic ICV administration of the orexins on feeding in the rat. Peptides 20, 10991105.
Hill, JO & Peters, JC (1998) Environmental contributions to the obesity epidemic. Science 280, 13711373.
Horvath, TL, Diano, S & van den Pol, AN (1999) Synaptic interaction between the hypocretin (orexin) and neuropeptide Y cells in the rodent and primate hypothalamus: A novel circuit implicated in metabolic and endocrine regulations. Journal of Neuroscience 19, 10721087.
Huszar, D, Lynch, CA, Fairchild-Huntress, V, Dunmore, JH, Fang, Q, Berkemeier, LR, Gu, W, Kesterson, RA, Boston, BA, Cone, RD, Smith, FJ, Campfield, LA, Burn, P & Lee, R (1997) Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88, 131141.
Ida, T, Nakahara, K, Katayama, T, Murakami, N & Nakazato, M (1999) Effect of lateral cerebroventricular injection of the appetite-stimulating neuropeptide, orexin and neuropeptide Y, on the various behavioral activities of rats. Brain Research 821, 526529.
Inui, A (1999) Neuropeptide Y feeding receptors: Are multiple subtypes involved? Trends in Pharmacological Sciences 20, 4346.
Jegou, S, Blasquez, C, Delbende, C, Bunel, DT & Vaundry, H (1993) Regulation of a-melanocyte-stimulating hormone release from hypothalamic neurons. Annals of the New York Academy of Sciences 680, 260278.
Kalra, SP, Dube, MG, Fournier, A & Kalra, PS (1991a) Structure-function analysis of stimulation of food intake by neuropeptide Y: Effect of receptor agonists. Physiology and Behavior 50, 59.
Kalra, SP, Dube, MG, Sahu, A, Phelps, C & Kalra, PS (1991b) Neuropeptide Y secretion increases in the paraventricular nucleus in association with increased appetite for food. Proceedings of the National Academy of Sciences USA 38, 1093110935.
Kesterson, RA, Huszar, D, Lynch, CA, Simerly, RB & Cone, RD (1997) Induction of neuropeptide Y gene expression in the dorsal medial hypothalamic nucleus in two models of the agouti obesity syndrome. Molecular Endocrinology 11, 630637.
Kiefer, LL, Ittoop, OR, Bunce, K, Truesdale, AT, Willard, DH, Nichols, JS, Blanchard, SG, Mountjoy, K, Chen, WJ & Wilkison, WO (1997) Mutations in the carboxyl terminus of agouti protein decrease agouti inhibition of ligand binding to the melanocortin receptors. Biochemistry 36, 20842090.
Krude, H, Biebermann, H, Luck, W, Horn, R, Brabant, G & Gruters, A (1998) Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nature Genetics 19, 155157.
Lin, L, Faraco, J, Li, R, Kadotani, H, Rogers, W, Lin, X, Qui, X, de Jong, PJ, Nishino, S & Mignot, E (1999) The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 98, 365376.
Lu, D, Willard, D, Patel, IR, Kadwell, S, Overton, L, Kost, T, Luther, M, Woychik, RP, Wilkison, WO & Cone, RD (1994) Agouti protein is an antagonist of the melanocyte stimulating-hormone receptor. Nature 371, 799802.
Lubkin, M & Stricker-Krongrad, A (1998) Independent feeding and metabolic actions of orexins in mice. Biochemical and Biophysical Research Communications 253, 241245.
McKibbin, PE, Cotton, SJ, McMillan, S, Holloway, B, Mayers, R, McCarthy, HD & Williams, G (1991) Altered neuropeptide Y concentrations in specific hypothalamic regions of obese (fa/fa) Zucker rats. Diabetes 40, 14231429.
Mizuno, TM, Kleopoulos, SP, Bergen, HT, Roberts, JL, Priest, CA & Mobbs, CV (1998) Hypothalamic pro-opiomelanocortin mRNA is reduced by fasting in ob/ob and db/db mice, but is stimulated by leptin. Diabetes 47, 294297.
Mondal, MS, Nakazato, M, Date, Y, Murakami, N, Yanagisawa, M & Matsukura, S (1999) Widespread distribution of orexin in rat brain and its regulation upon fasting. Biochemical and Biophysical Research Communications 256, 495499.
Moriguchi, T, Sakurai, T, Nambu, T, Yanagisawa, M & Goto, K (1999) Neurons containing orexin in the lateral hypothalamic area of the adult rat brain are activated by insulin-induced acute hypoglycemia. Neuroscience Letters 264, 101104.
Morris, BJ (1989) Neuronal localisation of neuropeptide Y gene expression in rat brain. Journal of Comparative Neurology 290, 358368.
Mountjoy, K, Mortrud, M, Low, M, Simerly, R & Cone, R (1994) Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Molecular Endocrinology 8, 12981308.
Nambu, T, Sakurai, T, Mizukami, K, Hosoya, Y, Yanagisawa, M & Goto, K (1999) Distribution of orexin neurons in the adult rat brain. Brain Research 827, 243260.
Ollmann, MM, Wilson, BD, Yang, Y-K, Kerns, JA, Chen, Y, Gantz, I & Barsh, GS (1997) Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 278, 135138.
Peyron, C, Tighe, DK, van den Pol, AN, de Lecea, L, Heller, HC, Sutcliffe, JG & Kilduff, TS (1998) Neurons containing hypocretin (orexin) project to multiple neuronal systems. Journal of Neuroscience 18, 999610015.
Phillips, MS, Liu, Q, Hammond, HA, Dugan, V, Hey, PJ, Caskey, CJ & Hess, JF (1996) Leptin receptor missense mutation in the fatty Zucker rat. Nature Genetics 13, 1819.
Pickavance, L, Dryden, S, Hopkins, D, Bing, C, Frankish, H, Wang, Q, Vernon, RG & Williams, G (1996) Relationships between hypothalamic neuropeptide Y and food intake in the lactating rat. Peptides 17, 577582.
Pu, S, Jain, MR, Kalra, PS & Kalra, SP (1998) Orexins, a novel family of hypothalamic neuropeptides, modulate pituitary luteinizing hormone secretion in an ovarian steroid-dependent manner. Regulatory Peptides 78, 133136.
Qu, D, Ludwig, DS, Gammeltoft, S, Piper, M, Pelleymounter, MA, Cullen, MJ, Mathes, WF, Przypek, J, Kanarek, R & Maratos-Flier, E (1996) A role for melanin-concentrating hormone in the central regulation of feeding behaviour. Nature 380, 243247.
Risold, PY, Griffond, B, Kilduff, TS, Sutcliffe, JG & Fellmann, D (1999) Preprohypocretin (orexin) and prolactin-like immunoreactivity are coexpressed by neurons of the rat lateral hypothalamic area. Neuroscience Letters 259, 153156.
Roselli-Rehfuss, L, Mountjoy, KG, Robbins, LS, Mortrud, MT, Low, MJ, Tatro, JB, Entwistle, ML, Simerly, RB & Cone, RD (1993) Identification of a receptor for g melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system. Proceedings of the National Academy of Sciences USA 90, 88568860.
Sakurai, T, Amemiya, A, Ishii, M, Matsuzaki, I, Chemelli, RM, Tanaka, H, Williams, SC, Richardson, JA, Kozlowski, GP, Wilson, S, Arch, JRS, Buckingham, RE, Haynes, AC, Carr, SA, Annan, RS, McNulty, DE, Liu, W-S, Terrett, JA, Elshourbagy, NA, Bergsma, DJ & Yanagisawa, M (1998) Orexins and orexin receptors: A family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 192, 573585.
Sakurai, T, Moriguchi, T, Furuya, K, Kajiwara, N, Nakamura, T, Yanagisawa, M & Goto, K (1999) Structure and function of human prepro-orexin gene. Journal of Biological Chemistry 274, 1777117776.
Samson, WK, Gosnell, B, Chang, J-K, Resch, ZT & Murphy, TC (1999) Cardiovascular regulatory actions of the hypocretins in brain. Brain Research 831, 248253.
Sanacora, G, Kershaw, M, Finkelstein, JA & White, JD (1990) Increased hypothalamic content of preproneuropeptide Y messenger ribonucleic acid in genetically obese Zucker rats and its regulation by food deprivation. Endocrinology 127, 730737.
Satoh, N, Ogawa, Y, Katsuura, G, Tsuji, T, Masuzaki, H, Hiraoka, J, Okazaki, T, Tamaki, M, Hayase, M, Yoshimasa, Y, Nishi, S, Hosoda, K & Nakao, K (1997) Pathophysiological significance of the obese gene product, leptin, in ventromedial hypothalamus (VMH)-lesioned rats: Evidence for the loss of its satiety effect in VMH-lesioned rats. Endocrinology 138, 947954.
Schaffauser, AO, Stricker-Krongrad, A, Brunner, L, Cumin, F, Gerald, C, Whitebread, S, Criscione, L & Hofbauer, KG (1997) Inhibition of food intake by neuropeptide Y Y5 receptor subtype antisense oligodeoxynucleotides. Diabetes 46, 17921798.
Schioth, HB, Muceniece, R, Mutulis, F, Bouifrouri, AA, Mutule, I & Wikberg, JES (1999) Further pharmacological characterisation of the selective melanocortin 4 receptor antagonist HS014: Comparison with SHU9119. Neuropeptides 33, 191196.
Schwartz, MW, Figlewicz, DP, Baskin, DG, Woods, SC & Porte, DJ (1992) Insulin in the brain: A hormonal regulator of energy balance. Endocrine Reviews 13, 387414.
Schwartz, MW, Seeley, RJ, Woods, SC, Weigle, DS, Campfield, LA, Burn, P & Baskin, DG (1997) Leptin increases hypothalamic proopiomelanocortin mRNA expression in the rostral arcuate nucleus. Diabetes 46, 21192123.
Seeley, RJ, Yagaloff, KA, Fisher, SL, Burn, P, Thiele, TE, van Dijk, G, Baskin, DG & Schwartz, MW (1997) Melanocortin receptors in leptin effects. Nature 390, 349.
Shutter, JR, Graham, M, Kinsey, AC, Scully, S, Luthy, R & Stark, KL (1997) Hypothalamic expression of ART, a novel gene related to agouti, is up-regulated in obese and diabetic mutant mice. Genes Development 11, 593602.
Siegel, JM (1999) Narcolepsy: A key role for hypocretins (orexins). Cell 98, 409412.
Sindelar, DK, Marsh, DJ, Mystkowski, PM, Palmiler, R & Schwartz, W (1999) Attenuation of diabetic hyperphagia in neuropeptide Y deficient mice. Diabetes 48, Suppl. 1, A26.
Smith, MS (1993) Lactation alters neuropeptide-Y and proopiomelanocortin gene expression in the arcuate nucleus of the rat. Endocrinology 133, 12581265.
Stephens, TW, Basinski, M, Bristow, PK, Bue-Valleskey, JM, Burgett, SG, Craft, L, Hales, J, Hoffmann, J, Hsiung, HM, Kriauciunas, A, MacKeller, W, Rosteck, PR, Schoner, B, Smith, D, Tinsley, FC, Zhang, XY & Heiman, M (1995) The role of neuropeptide Y in the antiobesity actions of the obese gene product. Nature 377, 530532.
Sweet, DC, Levine, AS, Billington, CJ & Kotz, CM (1999) Feeding response to central orexins. Brain Research 821, 535538.
Taheri, S, Mahmoodi, M, Opacka-Juffry, J, Ghatei, MA & Bloom, SR (1999) Distribution and quantification of immunoreactive orexin A in rat tissues. FEBS Letters 457, 157161.
Takahashi, N, Okumura, T, Yamada, H & Kohgo, Y (1999) Stimulation of gastric acid secretion by centrally administered orexin-A in conscious rats. Biochemical and Biophysical Research Communications 254, 623627.
Trivedi, P, Yu, H, MacNeil, DJ, Van der Ploeg, LHT & Guan, X-M (1998) Distribution of orexin receptor mRNA in the rat brain. FEBS Letters 438, 7175.
van den Pol, AN (1999) Hypothalamic hypocretin (orexin): Robust innervation of the spinal cord. Journal of Neuroscience 19, 31713182.
van den Pol, AN, Gao, X-B, Obrietan, K, Kilduff, TS & Belousov, AB (1998) Presynaptic and postsynaptic actions and modulation of neuroendocrine by a new hypothalamic peptide, hypocretin/ orexin. Journal of Neuroscience 19, 79627971.
Vettor, R, Zarjevski, N, Cusin, I, Rohner-Jeanrenaud, F & Jeanrenaud, B (1994) Induction and reversibility of an obesity syndrome by intracerebroventricular neuropeptide Y administration to normal rats. Diabetologia 37, 12021208.
Wang, Q, Bing, C, Al-Barazanji, K, Mossakowaska, DE, Wang, X-M, McBay, DL, Neville, WA, Taddayon, M, Pickavance, L, Dryden, S, Thomas, MEA, McHale, MT, Gloyer, IS, Wilson, S, Buckingham, R, Arch, JRS, Trayhurn, P & Williams, G (1997) Interactions between leptin and hypothalamic neuropeptide Y neurons in the control of food intake and energy homeostasis in the rat. Diabetes 46, 335341.
Widdowson, PS, Upton, R, Henderson, L, Buckingham, R, Wilson, S & Williams, G (1997) Reciprocal regional changes in brain NPY receptor density during dietary restriction and dietary-induced obesity in the rat. Brain Research 774, 110.
Wijker, M, Wszolek, ZK, Wolters, ECH, Rooimans, MA, Pals, G, Pfeiffer, RF, Lynch, T, Rodnitzky, RL, Wilhelmsen, KC & Arwert, F (1996) Localization of the gene for rapidly progressive autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration to chromosome 17q21. Human Molecular Genetics 5, 151154.
Wilding, JP, Gilbey, SG, Bailey, CJ, Batt, RA, Williams, G, Ghatei, MA & Bloom, SR (1993) Increased neuropeptide-Y messenger ribonucleic acid (mRNA) and decreased neurotensin mRNA in the hypothalamus of the obese (ob/ob) mouse. Endocrinology 132, 19391944.
Wilding, JP, Gilbey, SG, Mannan, M, Aslam, N, Ghatei, MA & Bloom, SR (1992) Increased neuropeptide Y content in individual hypothalamic nuclei, but not neuropeptide Y mRNA, in diet-induced obesity in rats. Journal of Endocrinology 132, 299304.
Wilhelmsen, KC, Lynch, T, Pavlou, E, Higgins, M & Hygaard, TG (1994) Localization of disinhibition-dementia-parkinsonism-amyotrophy complex to 17q21–22. American Journal of Human Genetics 55, 11591165.
Woods, SC, Seeley, RJ, Porte, D & Schwartz, MW (1998) Signals that regulate food intake and energy homeostasis. Science 280, 13781382.
Yamamoto, Y, Ueta, Y, Date, Y, Nakazato, M, Hara, Y, Serino, R, Nomura, M, Shibuya, I, Matsukura, S & Yamashita, H (1999) Down regulation of prepro-orexin gene expression in genetically obese mice. Molecular Brain Research 65, 1422.
Yeo, GSH, Farooqi, S, Aminian, S, Halsall, DJ, Stanhope, RG & O'Rahilly, S (1998) A frameshift mutation in MC4-R associated with dominantly inherited human obesity. Nature Genetics 20, 111112.
Zoli, M, Torri, C, Ferrari, R, Jansson, A, Zini, I, Fuxe, K & Agnati, LF (1998) The emergence of the volume transmission concept. Brain Research Reviews 26, 136147.


The hypothalamus and the regulation of energy homeostasis: lifting the lid on a black box

  • Gareth Williams (a1), Joanne A. Harrold (a1) and David J. Cutler (a1)


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