• 1
    Galbraith JK. The New Industrial State. Boston, MA: Houghton Mifflin, 1967.
  • 2
    World Health Organization. Obesity: Preventing and Managing the Global Epidemic. Geneva: World Health Organization, 2000.
  • 3
    National Task Force on the Prevention and Treatment of Obesity. Overweight, obesity, and health risk. Arch Intern Med 2000; 160: 898904.
  • 4
    World Health Organization. Diet, nutrition and the prevention of chronic diseases. World Health Organ Tech Rep Ser 2003; 916: iviii, 1–149, backcover.
  • 5
    Maclure KM, Hayes KC, Colditz GA, Stampfer MJ, Speizer FE, Willett WC. Weight, diet, and the risk of symptomatic gallstones in middle-aged women. N Engl J Med 1989; 321: 5639.
  • 6
    Felson DT, Anderson JJ, Naimark A, Walker AM, Meenan RF. Obesity and knee osteoarthritis. The Framingham Study. Ann Intern Med 1988; 109: 1824.
  • 7
    Grodstein F, Goldman MB, Cramer DW. Body mass index and ovulatory infertility. Epidemiology 1994; 5: 24750.
  • 8
    Rexrode KM, Hennekens CH, Willett WC et al. A prospective study of body mass index, weight change, and risk of stroke in women. JAMA 1997; 277: 153945.
  • 9
    Scheinfeld NS. Obesity and dermatology. Clin Dermatol 2004; 22: 3039.
  • 10
    Gottschlich MM, Mayes T, Khoury JC, Warden GD. Significance of obesity on nutritional, immunologic, hormonal, and clinical outcome parameters in burns. J Am Diet Assoc 1993; 93: 12618.
  • 11
    Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW Jr. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med 1999; 341: 1097105.
  • 12
    Puhl R, Brownell KD. Bias, discrimination, and obesity. Obes Res 2001; 9: 788805.
  • 13
    Pontiroli AE. Type 2 diabetes mellitus is becoming the most common type of diabetes in school children. Acta Diabetol 2004; 41: 8590.
  • 14
    Hoek HW, van Hoeken D. Review of the prevalence and incidence of eating disorders. Int J Eat Disord 2003; 34: 38396.
  • 15
    Plata-Salaman CR. Cytokines and feeding. News Physiol Sci 1998; 13: 298304.
  • 16
    Strasser F, Bruera ED. Update on anorexia and cachexia. Hematol Oncol Clin North Am 2002; 16: 589617.
  • 17
    Briefel RR, McDowell MA, Alaimo K et al. Total energy intake of the US population: the third National Health and Nutrition Examination Survey, 1988–1991. Am J Clin Nutr 1995; 62: 1072S80S.
  • 18
    Johnson D, Drenick EJ. Therapeutic fasting in morbid obesity. Arch Intern Med 1977; 137: 13812.
  • 19
    Mitchel JS, Keesey RE. Defense of a lowered weight maintenance level by lateral hypothamically lesioned rats: evidence from a restriction-refeeding regimen. Physiol Behav 1977; 18: 11215.
  • 20
    Sims EA, Danforth E Jr, Horton ES, Bray GA, Glennon JA, Salans LB. Endocrine and metabolic effects of experimental obesity in man. Recent Prog Horm Res 1973; 29: 45796.
  • 21
    Neel JV. Diabetes mellitus: a ‘‘thrifty’’ genotype rendered detrimental by ‘‘progress’’? Am J Hum Genet 1962; 14: 35362.
  • 22
    Farrigan C, Pang K. Obesity market overview. Nat Rev Drug Discov 2002; 1: 2578.
  • 23
    Sjöström L, Lindroos AK, Peltonen M et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 2004; 351: 268393.
  • 24
    Bergh C, Brodin U, Lindberg G, Sodersten P. Randomized controlled trial of a treatment for anorexia and bulimia nervosa. Proc Natl Acad Sci U S A 2002; 99: 948691.
  • 25
    Mohr B. Hypertrophie der Hypophysis cerebri und adurch bedingter Druck auf die Hirngrundfläche, ins besondere auf die Sehnerven, das Chiasma derselben und den linkseitigen Hirnschenkel. Wschr ges Heilk 1840; 6: 56571.
  • 26
    Babinski MJ. Tumeur du corps pituitaire sans acromégalie et avec arrêt de développement des organes génitaux. Rev Neurol 1900; 8: 5313.
  • 27
    Fröhlich A. Ein Fall von Tumor der Hypophysis cerebri ohne Akromegalie. Wien Klin Rundschau 1901; 15: 8836, 9068.
  • 28
    Bray GA, Gallagher TF Jr. Manifestations of hypothalamic obesity in man: a comprehensive investigation of eight patients and a review of the literature. Medicine (Baltimore) 1975; 54: 30130.
  • 29
    Aschner B. Über die funktion der hypophyse. Arch f d ges Physiol 1912; 146: 1146.
  • 30
    Hetherington AW, Ranson SW. Hypothalamic lesions and adiposity in the rat. Anat Rec 1940; 78: 14972.
  • 31
    Anand BK, Brobeck JR. Hypothalamic control of food intake in rats and cats. Yale J Biol Med 1951; 24: 12340.
  • 32
    Anand BK, Brobeck JR. Localization of a ‘‘feeding center’’ in the hypothalamus of the rat. Proc Soc Exp Biol Med 1951; 77: 3234.
  • 33
    Grill HJ, Norgren R. Chronically decerebrate rats demonstrate satiation but not bait shyness. Science 1978; 201: 2679.
  • 34
    Kennedy GC. The role of depot fat in the hypothalamic control of food intake in the rat. Proc R Soc Lond B Biol Sci 1953; 140: 57896.
  • 35
    MacLagan NF. The role of appetite in the control of body weight. J Physiol 1937; 90: 38594.
  • 36
    Stellar E. The physiology of motivation. Psychol Rev 1954; 61: 522.
  • 37
    Berthoud HR. Multiple neural systems controlling food intake and body weight. Neurosci Biobehav Rev 2002; 26: 393428.
  • 38
    Grill HJ, Kaplan JM. The neuroanatomical axis for control of energy balance. Front Neuroendocrinol 2002; 23: 240.
  • 39
    Khosla T, Billewicz WZ. Measurement of change in body-weight. Br J Nutr 1964; 18: 22739.
  • 40
    Broberger C, Hökfelt T. Hypothalamic and vagal neuropeptide circuitries regulating food intake. Physiol Behav 2001; 74: 66982.
  • 41
    Ramón y Cajal S. Histologie du système nerveux de l'homme et des vertébrés. Oxford: Oxford University Press (republ. 1995), 1909.
  • 42
    Harding R, Leek BF. Central projections of gastric afferent vagal inputs. J Physiol 1973; 228: 7390.
  • 43
    Appleyard SM, Bailey TW, Doyle MW et al. Proopiomelanocortin neurons in nucleus tractus solitarius are activated by visceral afferents: regulation by cholecystokinin and opioids. J Neurosci 2005; 25: 357885.
  • 44
    Swanson LW, Mogenson GJ. Neural mechanisms for the functional coupling of autonomic, endocrine and somatomotor responses in adaptive behavior. Brain Res 1981; 228: 134.
  • 45
    Smith GP. The direct and indirect controls of meal size. Neurosci Biobehav Rev 1996; 20: 416.
  • 46
    Sclafani A, Ackroff K, Schwartz GJ. Selective effects of vagal deafferentation and celiac-superior mesenteric ganglionectomy on the reinforcing and satiating action of intestinal nutrients. Physiol Behav 2003; 78: 28594.
  • 47
    Gibbs J, Young RC, Smith GP. Cholecystokinin decreases food intake in rats. J Comp Physiol Psychol 1973; 84: 48895.
  • 48
    Smith GP, Jerome C, Cushin BJ, Eterno R, Simansky KJ. Abdominal vagotomy blocks the satiety effect of cholecystokinin in the rat. Science 1981; 213: 10367.
  • 49
    Schwartz GJ, McHugh PR, Moran TH. Integration of vagal afferent responses to gastric loads and cholecystokinin in rats. Am J Physiol Regul Integr Comp Physiol 1991; 261: R649.
  • 50
    Schwartz GJ, McHugh PR, Moran TH. Gastric loads and cholecystokinin synergistically stimulate rat gastric vagal afferents. Am J Physiol Regul Integr Comp Physiol 1993; 265: R8726.
  • 51
    Sykes RM, Spyer KM, Izzo PN. Demonstration of glutamate immunoreactivity in vagal sensory afferents in the nucleus tractus solitarius of the rat. Brain Res 1997; 762: 111.
  • 52
    Broberger C, Holmberg K, Kuhar MJ, Hökfelt T. Cocaine- and amphetamine-regulated transcript in the rat vagus nerve: a putative mediator of cholecystokinin-induced satiety. Proc Natl Acad Sci U S A 1999; 96: 1350611.
  • 53
    Aja S, Schwartz GJ, Kuhar MJ, Moran TH. Intracerebroventricular CART peptide reduces rat ingestive behavior and alters licking microstructure. Am J Physiol Regul Integr Comp Physiol 2001; 280: R16139.
  • 54
    Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 42532.
  • 55
    Ahima RS, Prabakaran D, Mantzoros C et al. Role of leptin in the neuroendocrine response to fasting. Nature 1996; 382: 2502.
  • 56
    Halaas JL, Gajiwala KS, Maffei M et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995; 269: 5436.
  • 57
    Maffei M, Halaas J, Ravussin E et al. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1995; 1: 115561.
  • 58
    Flier JS. Obesity wars: molecular progress confronts an expanding epidemic. Cell 2004; 116: 33750.
  • 59
    Cohen P, Zhao C, Cai X et al. Selective deletion of leptin receptor in neurons leads to obesity. J Clin Invest 2001; 108: 111321.
  • 60
    Woods SC, Lotter EC, McKay LD, Porte D Jr. Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons. Nature 1979; 282: 5035.
  • 61
    Obici S, Feng Z, Karkanias G, Baskin DG, Rossetti L. Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats. Nat Neurosci 2002; 5: 56672.
  • 62
    Nicolaïdis S, Rowland N. Metering of intravenous versus oral nutrients and regulation of energy balance. Am J Physiol 1976; 231: 6618.
  • 63
    Woods SC, Stein LJ, McKay LD, Porte D Jr. Suppression of food intake by intravenous nutrients and insulin in the baboon. Am J Physiol 1984; 247: R393401.
  • 64
    Parra-Covarrubias A, Rivera-Rodriguez I, Almaraz-Ugalde A. Cephalic phase of insulin secretion in obese adolescents. Diabetes 1971; 20: 8002.
  • 65
    Obici S, Zhang BB, Karkanias G, Rossetti L. Hypothalamic insulin signaling is required for inhibition of glucose production. Nat Med 2002; 8: 137682.
  • 66
    Pocai A, Obici S, Schwartz GJ, Rossetti L. A brain-liver circuit regulates glucose homeostasis. Cell Metab 2005; 1: 5361.
  • 67
    Strader AD, Woods SC. Gastrointestinal hormones and food intake. Gastroenterology 2005; 128: 17591.
  • 68
    Lundberg JM, Tatemoto K, Terenius L et al. Localization of peptide YY (PYY) in gastrointestinal endocrine cells and effects on intestinal blood flow and motility. Proc Natl Acad Sci U S A 1982; 79: 44715.
  • 69
    Adrian TE, Ferri GL, Bacarese-Hamilton AJ, Fuessl HS, Polak JM, Bloom SR. Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology 1985; 89: 10707.
  • 70
    Adrian TE, Bacarese-Hamilton AJ, Smith HA, Chohan P, Manolas KJ, Bloom SR. Distribution and postprandial release of porcine peptide YY. J Endocrinol 1987; 113: 1114.
  • 71
    Greeley GH Jr, Hashimoto T, Izukura M et al. A comparison of intraduodenally and intracolonically administered nutrients on the release of peptide-YY in the dog. Endocrinology 1989; 125: 17615.
  • 72
    Morley JE, Flood JF. An investigation of tolerance to the actions of leptogenic and anorexigenic drugs in mice. Life Sci 1987; 41: 215765.
  • 73
    Batterham RL, Cowley MA, Small CJ et al. Gut hormone PYY(3-36) physiologically inhibits food intake. Nature 2002; 418: 6504.
  • 74
    Tschöp M, Castaneda TR, Joost HG et al. Physiology: does gut hormone PYY3-36 decrease food intake in rodents? Nature 2004, 430: 165.
  • 75
    Batterham RL, Cowley MA, Small CJ et al. Physiology: does gut hormone PYY3-36 decrease food intake in rodents? (reply). Nature 2004; 430: 165.
  • 76
    Halatchev IG, Ellacott KL, Fan W, Cone RD. Peptide YY3-36 inhibits food intake in mice through a melanocortin-4 receptor-independent mechanism. Endocrinology 2004; 145: 258590.
  • 77
    Pittner RA, Moore CX, Bhavsar SP et al. Effects of PYY[3-36] in rodent models of diabetes and obesity. Int J Obes Relat Metab Disord 2004; 28: 96371.
  • 78
    Batterham RL, Bloom SR. The gut hormone peptide YY regulates appetite. Ann N Y Acad Sci 2003; 994: 1628.
  • 79
    Imamura M, Takahashi H, Mikami Y, Yamauchi H. Elevation of plasma peptide YY and pancreatic juice hypersecretion following massive small bowel resection in the rat. Tohoku J Exp Med 1998; 184: 4959.
  • 80
    Adrian TE, Savage AP, Fuessl HS, Wolfe K, Besterman HS, Bloom SR. Release of peptide YY (PYY) after resection of small bowel, colon, or pancreas in man. Surgery 1987; 101: 7159.
  • 81
    Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999; 402: 65660.
  • 82
    Kojima M, Kangawa K. Ghrelin: structure and function. Physiol Rev 2005; 85: 495522.
  • 83
    Wren AM, Small CJ, Ward HL et al. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 2000; 141: 43258.
  • 84
    Wren AM, Small CJ, Abbott CR et al. Ghrelin causes hyperphagia and obesity in rats. Diabetes 2001; 50: 25407.
  • 85
    Nakazato M, Murakami N, Date Y et al. A role for ghrelin in the central regulation of feeding. Nature 2001; 409: 1948.
  • 86
    Tschöp M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes 2001; 50: 7079.
  • 87
    Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 2001; 50: 17149.
  • 88
    Masuda Y, Tanaka T, Inomata N et al. Ghrelin stimulates gastric acid secretion and motility in rats. Biochem Biophys Res Commun 2000; 276: 9058.
  • 89
    Date Y, Murakami N, Toshinai K et al. The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology 2002; 123: 11208.
  • 90
    Wang L, Saint-Pierre DH, Tache Y. Peripheral ghrelin selectively increases Fos expression in neuropeptide Y-synthesizing neurons in mouse hypothalamic arcuate nucleus. Neurosci Lett 2002; 325: 4751.
  • 91
    Shintani M, Ogawa Y, Ebihara K et al. Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. Diabetes 2001; 50: 22732.
  • 92
    Lu S, Guan JL, Wang QP et al. Immunocytochemical observation of ghrelin-containing neurons in the rat arcuate nucleus. Neurosci Lett 2002; 321: 15760.
  • 93
    Cowley MA, Smith RG, Diano S et al. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 2003; 37: 64961.
  • 94
    Näslund E, Hellström PM, Kral JG. The gut and food intake: an update for surgeons. J Gastrointest Surg 2001; 5: 55667.
  • 95
    Mason EE, Ito C. Gastric bypass in obesity. Surg Clin North Am 1967; 47: 134551.
  • 96
    Halmi KA, Mason E, Falk JR, Stunkard A. Appetitive behavior after gastric bypass for obesity. Int J Obes 1981; 5: 45764.
  • 97
    Cummings DE, Weigle DS, Frayo RS et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 2002; 346: 162330.
  • 98
    Cummings DE, Clement K, Purnell JQ et al. Elevated plasma ghrelin levels in Prader Willi syndrome. Nat Med 2002; 8: 6434.
  • 99
    Hollister LE. Hunger and appetite after single doses of marihuana, alcohol, and dextroamphetamine. Clin Pharmacol Ther 1971; 12: 4449.
  • 100
    American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Washington, DC: American Psychiatric Association, 1994.
  • 101
    Piomelli D. The molecular logic of endocannabinoid signalling. Nat Rev Neurosci 2003; 4: 87384.
  • 102
    Williams CM, Kirkham TC. Anandamide induces overeating: mediation by central cannabinoid (CB1) receptors. Psychopharmacology (Berl) 1999; 143: 3157.
  • 103
    Berry EM, Mechoulam R. Tetrahydrocannabinol and endocannabinoids in feeding and appetite. Pharmacol Ther 2002; 95: 18590.
  • 104
    Rodriguez de Fonseca F, Navarro M, Gomez R et al. An anorexic lipid mediator regulated by feeding. Nature 2001; 414: 20912.
  • 105
    Gaetani S, Cuomo V, Piomelli D. Anandamide hydrolysis: a new target for anti-anxiety drugs? Trends Mol Med 2003; 9: 4748.
  • 106
    Guzman M, Lo Verme J, Fu J, Oveisi F, Blazquez C, Piomelli D. Oleoylethanolamide stimulates lipolysis by activating the nuclear receptor peroxisome proliferator-activated receptor alpha (PPAR-alpha). J Biol Chem 2004; 279: 2784954.
  • 107
    Fu J, Gaetani S, Oveisi F et al. Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature 2003; 425: 903.
  • 108
    Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 1990; 347: 64550.
  • 109
    Schwartz MW, Marks JL, Sipols AJ et al. Central insulin administration reduces neuropeptide Y mRNA expression in the arcuate nucleus of food-deprived lean (Fa/Fa) but not obese (fa/fa) Zucker rats. Endocrinology 1991; 128: 26457.
  • 110
    Schwartz MW, Seeley RJ, Woods SC et al. Leptin increases hypothalamic pro-opiomelanocortin mRNA expression in the rostral arcuate nucleus. Diabetes 1997; 46: 211923.
  • 111
    Thornton JE, Cheung CC, Clifton DK, Steiner RA. Regulation of hypothalamic proopiomelanocortin mRNA by leptin in ob/ob mice. Endocrinology 1997; 138: 50636.
  • 112
    Kim EM, Grace MK, Welch CC, Billington CJ, Levine AS. STZ-induced diabetes decreases and insulin normalizes POMC mRNA in arcuate nucleus and pituitary in rats. Am J Physiol 1999; 276: R13206.
  • 113
    Elias CF, Aschkenasi C, Lee C et al. Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area. Neuron 1999; 23: 77586.
  • 114
    Levin BE, Routh VH, Kang L, Sanders NM, Dunn-Meynell AA. Neuronal glucosensing: what do we know after 50 years? Diabetes 2004; 53: 25218.
  • 115
    Spanswick D, Smith MA, Groppi VE, Logan SD, Ashford ML. Leptin inhibits hypothalamic neurons by activation of ATP-sensitive potassium channels. Nature 1997; 390: 5215.
  • 116
    Spanswick D, Smith MA, Mirshamsi S, Routh VH, Ashford ML. Insulin activates ATP-sensitive K+ channels in hypothalamic neurons of lean, but not obese rats. Nat Neurosci 2000; 3: 7578.
  • 117
    Niswender KD, Morton GJ, Stearns WH, Rhodes CJ, Myers MG Jr, Schwartz MW. Intracellular signalling. Key enzyme in leptin-induced anorexia. Nature 2001; 413: 7945.
  • 118
    Dunn-Meynell AA, Rawson NE, Levin BE. Distribution and phenotype of neurons containing the ATP-sensitive K+ channel in rat brain. Brain Res 1998; 814: 4154.
  • 119
    Ibrahim N, Bosch MA, Smart JL et al. Hypothalamic proopiomelanocortin neurons are glucose responsive and express K(ATP) channels. Endocrinology 2003; 144: 133140.
  • 120
    Wang R, Liu X, Hentges ST et al. The regulation of glucose-excited neurons in the hypothalamic arcuate nucleus by glucose and feeding-relevant peptides. Diabetes 2004; 53: 195965.
  • 121
    Obici S, Feng Z, Arduini A, Conti R, Rossetti L. Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production. Nat Med 2003; 9: 75661.
  • 122
    Pocai A, Lam TK, Gutierrez-Juarez R et al. Hypothalamic K(ATP) channels control hepatic glucose production. Nature 2005; 434: 102631.
  • 123
    Coppari R, Ichinose M, Lee CE et al. The hypothalamic arcuate nucleus: a key site for mediating leptin's effects on glucose homeostasis and locomotor activity. Cell Metab 2005; 1: 6372.
  • 124
    Stanley BG, Magdalin W, Seirafi A, Thomas WJ, Leibowitz SF. The perifornical area: the major focus of (a) patchily distributed hypothalamic neuropeptide Y-sensitive feeding system(s). Brain Res 1993; 604: 30417.
  • 125
    Erickson JC, Clegg KE, Palmiter RD. Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y. Nature 1996; 381: 41521.
  • 126
    Bannon AW, Seda J, Carmouche M et al. Behavioral characterization of neuropeptide Y knockout mice. Brain Res 2000; 868: 7987.
  • 127
    Erickson JC, Hollopeter G, Palmiter RD. Attenuation of the obesity syndrome of ob/ob mice by the loss of neuropeptide Y. Science 1996; 274: 17047.
  • 128
    Lin S, Boey D, Herzog H. NPY and Y receptors: lessons from transgenic and knockout models. Neuropeptides 2004; 38: 189200.
  • 129
    McCrea K, Wisialowski T, Cabrele C et al. 2–36[K4, RYYSA(19–23)]PP a novel Y5-receptor preferring ligand with strong stimulatory effect on food intake. Regul Pept 2000; 87: 4758.
  • 130
    Ammar AA, Sederholm F, Saito TR, Scheurink AJ, Johnson AE, Sodersten P. NPY-leptin: opposing effects on appetitive and consummatory ingestive behavior and sexual behavior. Am J Physiol Regul Integr Comp Physiol 2000; 278: R162733.
  • 131
    Poggioli R, Vergoni AV, Bertolini A. ACTH-(1-24) and alpha-MSH antagonize feeding behavior stimulated by kappa opiate agonists. Peptides 1986; 7: 8438.
  • 132
    Fan W, Boston BA, Kesterson RA, Hruby VJ, Cone RD. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature 1997; 385: 1658.
  • 133
    Huszar D, Lynch CA, Fairchild-Huntress V et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 1997; 88: 13141.
  • 134
    Yaswen L, Diehl N, Brennan MB, Hochgeschwender U. Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin. Nat Med 1999; 5: 106670.
  • 135
    Butler AA, Kesterson RA, Khong K et al. A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Endocrinology 2000; 141: 351821.
  • 136
    Butler AA, Marks DL, Fan W, Kuhn CM, Bartolome M, Cone RD. Melanocortin-4 receptor is required for acute homeostatic responses to increased dietary fat. Nat Neurosci 2001; 4: 60511.
  • 137
    Swanson LW, Kuypers HG. The paraventricular nucleus of the hypothalamus: cytoarchitectonic subdivisions and organization of projections to the pituitary, dorsal vagal complex, and spinal cord as demonstrated by retrograde fluorescence double-labeling methods. J Comp Neurol 1980; 194: 55570.
  • 138
    Cechetto DF, Saper CB. Neurochemical organization of the hypothalamic projection to the spinal cord in the rat. J Comp Neurol 1988; 272: 579604.
  • 139
    Elias CF, Lee C, Kelly J et al. Leptin activates hypothalamic CART neurons projecting to the spinal cord. Neuron 1998; 21: 137585.
  • 140
    Farooqi IS, Keogh JM, Yeo GS, Lank EJ, Cheetham T, O'Rahilly S. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med 2003; 348: 108595.
  • 141
    Ollmann MM, Wilson BD, Yang YK et al. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 1997; 278: 1358.
  • 142
    Broberger C, De Lecea L, Sutcliffe JG, Hökfelt T. 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. J Comp Neurol 1998; 402: 46074.
  • 143
    Hahn TM, Breininger JF, Baskin DG, Schwartz MW. Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons. Nat Neurosci 1998; 1: 2712.
  • 144
    Hagan MM, Rushing PA, Pritchard LM et al. Long-term orexigenic effects of AgRP-(83-132) involve mechanisms other than melanocortin receptor blockade. Am J Physiol Regul Integr Comp Physiol 2000; 279: R4752.
  • 145
    Csiffáry A, Görcs TJ, Palkovits M. Neuropeptide Y innervation of ACTH-immunoreactive neurons in the arcuate nucleus of rats: a correlated light and electron microscopic double immunolabeling study. Brain Res 1990; 506: 21522.
  • 146
    Broberger C, Landry M, Wong H, Walsh JN, Hökfelt T. Subtypes Y1 and Y2 of the neuropeptide Y receptor are respectively expressed in pro-opiomelanocortin- and neuropeptide-Y-containing neurons of the rat hypothalamic arcuate nucleus. Neuroendocrinology 1997; 66: 393408.
  • 147
    Roseberry AG, Liu H, Jackson AC, Cai X, Friedman JM. Neuropeptide Y-mediated inhibition of proopiomelanocortin neurons in the arcuate nucleus shows enhanced desensitization in ob/ob mice. Neuron 2004; 41: 71122.
  • 148
    Dumont Y, Fournier A, St-Pierre S, Quirion R. Characterization of neuropeptide Y binding sites in rat brain membrane preparations using [125I][Leu31, Pro34]peptide YY and [125I]peptide YY3-36 as selective Y1 and Y2 radioligands. J Pharmacol Exp Ther 1995; 272: 67380.
  • 149
    Decavel C, Van den Pol AN. GABA: a dominant neurotransmitter in the hypothalamus. J Comp Neurol 1990; 302: 101937.
  • 150
    van den Pol AN, Wuarin JP, Dudek FE. Glutamate, the dominant excitatory transmitter in neuroendocrine regulation. Science 1990; 250: 12768.
  • 151
    van den Pol AN. Weighing the role of hypothalamic feeding neurotransmitters. Neuron 2003; 40: 105961.
  • 152
    Hökfelt T, Johansson O, Ljungdahl Å, Lundberg JM, Schultzberg M. Peptidergic neurones. Nature 1980; 284: 51521.
  • 153
    Stanley BG, Willett VL, III, Donias HW, Ha LH, Spears LC. The lateral hypothalamus: a primary site mediating excitatory amino acid-elicited eating. Brain Res 1993; 630: 419.
  • 154
    Stanley BG, Willett VL, III, Donias HW, Dee MG, II, Duva MA. Lateral hypothalamic NMDA receptors and glutamate as physiological mediators of eating and weight control. Am J Physiol 1996; 270: R4439.
  • 155
    Horvath TL, Bechmann I, Naftolin F, Kalra SP, Leranth C. Heterogeneity in the neuropeptide Y-containing neurons of the rat arcuate nucleus: GABAergic and non-GABAergic subpopulations. Brain Res 1997; 756: 2836.
  • 156
    Collin M, Backberg M, Ovesjo ML et al. Plasma membrane and vesicular glutamate transporter mRNAs/proteins in hypothalamic neurons that regulate body weight. Eur J Neurosci 2003; 18: 126578.
  • 157
    Cowley MA, Pronchuk N, Fan W, Dinulescu DM, Colmers WF, Cone RD. Integration of NPY, AGRP, and melanocortin signals in the hypothalamic paraventricular nucleus: evidence of a cellular basis for the adipostat. Neuron 1999; 24: 15563.
  • 158
    Pronchuk N, Beck-Sickinger AG, Colmers WF. Multiple NPY receptors inhibit GABA(A) synaptic responses of rat medial parvocellular effector neurons in the hypothalamic paraventricular nucleus. Endocrinology 2002; 143: 53543.
  • 159
    Wahlestedt C, Yanaihara N, Hakanson R. Evidence for different pre- and post-junctional receptors for neuropeptide Y and related peptides. Regul Pept 1986; 13: 30718.
  • 160
    Kopp J, Xu ZQ, Zhang X et al. Expression of the neuropeptide Y Y1 receptor in the CNS of rat and of wild-type and Y1 receptor knock-out mice. Focus on immunohistochemical localization. Neuroscience 2002; 111: 443532.
  • 161
    Elias CF, Saper CB, Maratos-Flier E et al. Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area. J Comp Neurol 1998; 402: 44259.
  • 162
    Peyron C, Tighe DK, van den Pol AN et al. Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 1998; 18: 999610015.
  • 163
    Chemelli RM, Willie JT, Sinton CM et al. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 1999; 98: 43751.
  • 164
    Lin L, Faraco J, Li R et al. The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 1999; 98: 36576.
  • 165
    Peyron C, Faraco J, Rogers W et al. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med 2000; 6: 9917.
  • 166
    Thannickal TC, Moore RY, Nienhuis R et al. Reduced number of hypocretin neurons in human narcolepsy. Neuron 2000; 27: 46974.
  • 167
    Verret L, Goutagny R, Fort P et al. A role of melanin-concentrating hormone producing neurons in the central regulation of paradoxical sleep. BMC Neurosci 2003; 4: 19.
  • 168
    Fu LY, Acuna-Goycolea C, van den Pol AN. Neuropeptide Y inhibits hypocretin/orexin neurons by multiple presynaptic and postsynaptic mechanisms: tonic depression of the hypothalamic arousal system. J Neurosci 2004; 24: 874151.
  • 169
    van den Pol AN, Acuna-Goycolea C, Clark KR, Ghosh PK. Physiological properties of hypothalamic MCH neurons identified with selective expression of reporter gene after recombinant virus infection. Neuron 2004; 42: 63552.
  • 170
    Campbell RE, Smith MS, Allen SE, Grayson BE, Ffrench-Mullen JM, Grove KL. Orexin neurons express a functional pancreatic polypeptide Y4 receptor. J Neurosci 2003; 23: 148797.
  • 171
    Turek FW, Joshu C, Kohsaka A et al. Obesity and metabolic syndrome in circadian Clock mutant mice. Science 2005; 308: 10435.
  • 172
    Kreier F, Yilmaz A, Kalsbeek A et al. Hypothesis: shifting the equilibrium from activity to food leads to autonomic unbalance and the metabolic syndrome. Diabetes 2003; 52: 26526.
  • 173
    Buijs RM, la Fleur SE, Wortel J et al. The suprachiasmatic nucleus balances sympathetic and parasympathetic output to peripheral organs through separate preautonomic neurons. J Comp Neurol 2003; 464: 3648.
  • 174
    Moore RY, Eichler VB. Loss of a circadian adrenal corticosterone rhythm following suprachiasmatic lesions in the rat. Brain Res 1972; 42: 2016.
  • 175
    Stephan FK, Zucker I. Circadian rhythms in drinking behavior and locomotor activity of rats are eliminated by hypothalamic lesions. Proc Natl Acad Sci U S A 1972; 69: 15836.
  • 176
    Kreier F, Fliers E, Voshol PJ et al. Selective parasympathetic innervation of subcutaneous and intra-abdominal fat – functional implications. J Clin Invest 2002; 110: 124350.
  • 177
    Karlsson B, Knutsson A, Lindahl B. Is there an association between shift work and having a metabolic syndrome? Results from a population based study of 27,485 people. Occup Environ Med 2001; 58: 74752.
  • 178
    Sekine M, Yamagami T, Handa K et al. A dose-response relationship between short sleeping hours and childhood obesity: results of the Toyama Birth Cohort Study. Child Care Health Dev 2002; 28: 16370.
  • 179
    Sinha MK, Ohannesian JP, Heiman ML et al. Nocturnal rise of leptin in lean, obese, and non-insulin-dependent diabetes mellitus subjects. J Clin Invest 1996; 97: 13447.
  • 180
    Vague J. The degree of masculine differentiation of obesities: a factor determining predisposition to diabetes, atherosclerosis, gout, and uric calculous disease. Am J Clin Nutr 1956; 4: 2034.
  • 181
    Davis JD, Smith GP. Learning to sham feed: behavioral adjustments to loss of physiological postingestional stimuli. Am J Physiol 1990; 259: R122835.
  • 182
    Schwartz GJ, Salorio CF, Skoglund C, Moran TH. Gut vagal afferent lesions increase meal size but do not block gastric preload-induced feeding suppression. Am J Physiol 1999; 276: R16239.
  • 183
    Erdheim J. Über Hypophysengangsgeschwülste und Hirncholesteatome. Sitzungsb d k Akad d Wissensch Math-naturw Cl Wien 1904; 113: 537726.
  • 184
    Olney JW. Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science 1969; 164: 71921.
  • 185
    Bugarith K, Dinh TT, Li AJ, Speth RC, Ritter S. Basomedial hypothalamic injections of neuropeptide Y conjugated to saporin selectively disrupt hypothalamic controls of food intake. Endocrinology 2005; 146: 117991.
  • 186
    Grill HJ, Schwartz MW, Kaplan JM, Foxhall JS, Breininger J, Baskin DG. Evidence that the caudal brainstem is a target for the inhibitory effect of leptin on food intake. Endocrinology 2002; 143: 23946.
  • 187
    Hosoi T, Kawagishi T, Okuma Y, Tanaka J, Nomura Y. Brain stem is a direct target for leptin's action in the central nervous system. Endocrinology 2002; 143: 3498504.
  • 188
    Huo L, Grill HJ, Bjorbaek C. Leptin-dependent activation of STAT3 phosphorylation in the medial sub-nucleus of the nucleus of the solitary tract (NTS) and regulation of pro-opiomelanocortin (POMC), pro-glucagon and galanin-like-peptide (GALP) mRNA. In Endocrine Society Proceedings, San Francisco, CA, USA, 2005.
  • 189
    Grill HJ, Ginsberg AB, Seeley RJ, Kaplan JM. Brainstem application of melanocortin receptor ligands produces long-lasting effects on feeding and body weight. J Neurosci 1998; 18: 1012835.
  • 190
    Fan W, Ellacott KL, Halatchev IG, Takahashi K, Yu P, Cone RD. Cholecystokinin-mediated suppression of feeding involves the brainstem melanocortin system. Nat Neurosci 2004; 7: 3356.
  • 191
    Faulconbridge LF, Cummings DE, Kaplan JM, Grill HJ. Hyperphagic effects of brainstem ghrelin administration. Diabetes 2003; 52: 22605.
  • 192
    Mizuno Y, Oomura Y. Glucose responding neurons in the nucleus tractus solitarius of the rat: in vitro study. Brain Res 1984; 307: 10916.
  • 193
    Morton GJ, Blevins JE, Williams DL et al. Leptin action in the forebrain regulates the hindbrain response to satiety signals. J Clin Invest 2005; 115: 70310.
  • 194
    Eskay RL, Giraud P, Oliver C, Brown-Stein MJ. Distribution of alpha-melanocyte-stimulating hormone in the rat brain: evidence that alpha-MSH-containing cells in the arcuate region send projections to extrahypothalamic areas. Brain Res 1979; 178: 5567.
  • 195
    Sim LJ, Joseph SA. Arcuate nucleus projections to brainstem regions which modulate nociception. J Chem Neuroanat 1991; 4: 97109.
  • 196
    Broberger C, Johansen J, Johansson C, Schalling M, Hökfelt T. The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice. Proc Natl Acad Sci U S A 1998; 95: 150438.
  • 197
    Bouret SG, Draper SJ, Simerly RB. Formation of projection pathways from the arcuate nucleus of the hypothalamus to hypothalamic regions implicated in the neural control of feeding behavior in mice. J Neurosci 2004; 24: 2797805.
  • 198
    Saper CB. Organization of cerebral cortical afferent systems in the rat. II. Hypothalamocortical projections. J Comp Neurol 1985; 237: 2146.
  • 199
    Kishi T, Aschkenasi CJ, Choi BJ et al. Neuropeptide Y Y1 receptor mRNA in rodent brain: distribution and colocalization with melanocortin-4 receptor. J Comp Neurol 2005; 482: 21743.
  • 200
    Norgren R. Projections from the nucleus of the solitary tract in the rat. Neuroscience 1978; 3: 20718.
  • 201
    Ricardo JA, Koh ET. Anatomical evidence of direct projections from the nucleus of the solitary tract to the hypothalamus, amygdala, and other forebrain structures in the rat. Brain Res 1978; 153: 126.
  • 202
    ter Horst GJ, de Boer P, Luiten PG, van Willigen JD. Ascending projections from the solitary tract nucleus to the hypothalamus. A Phaseolus vulgaris lectin tracing study in the rat. Neuroscience 1989; 31: 78597.
  • 203
    DeFalco J, Tomishima M, Liu H et al. Virus-assisted mapping of neural inputs to a feeding center in the hypothalamus. Science 2001; 291: 260813.
  • 204
    McCormick DA. Cortical and subcortical generators of normal and abnormal rhythmicity. Int Rev Neurobiol 2002; 49: 99114.
  • 205
    Thompson RH, Swanson LW. Structural characterization of a hypothalamic visceromotor pattern generator network. Brain Res Brain Res Rev 2003; 41: 153202.
  • 206
    Swanson LW. Cerebral hemisphere regulation of motivated behavior. Brain Res 2000; 886: 11364.
  • 207
    Choi GB, Dong HW, Murphy AJ et al. Lhx6 delineates a pathway mediating innate reproductive behaviors from the amygdala to the hypothalamus. Neuron 2005; 46: 64760.
  • 208
    Bargmann W. Über die neurosekretorische verknüpfung von hypothalamus und neurohypophyse. Z Zellforsch Mikr 1949; 34: 61034.
  • 209
    Saper CB, Loewy AD, Swanson LW, Cowan WM. Direct hypothalamo-autonomic connections. Brain Res 1976; 117: 30512.
  • 210
    Swanson LW, Sawchenko PE. Hypothalamic integration: organization of the paraventricular and supraoptic nuclei. Annu Rev Neurosci 1983; 6: 269324.
  • 211
    Hodgkin J, Doniach T. Natural variation and copulatory plug formation in Caenorhabditis elegans. Genetics 1997; 146: 14964.
  • 212
    de Bono M, Bargmann CI. Natural variation in a neuropeptide Y receptor homolog modifies social behavior and food response in C. elegans. Cell 1998; 94: 67989.
  • 213
    de Bono M. Molecular approaches to aggregation behavior and social attachment. J Neurobiol 2003; 54: 7892.
  • 214
    Rogers C, Reale V, Kim K et al. Inhibition of Caenorhabditis elegans social feeding by FMRFamide-related peptide activation of NPR-1. Nat Neurosci 2003; 6: 117885.
  • 215
    Cheung BH, Arellano-Carbajal F, Rybicki I, de Bono M. Soluble guanylate cyclases act in neurons exposed to the body fluid to promote C. elegans aggregation behavior. Curr Biol 2004; 14: 110511.
  • 216
    Gray JM, Karow DS, Lu H et al. Oxygen sensation and social feeding mediated by a C. elegans guanylate cyclase homologue. Nature 2004; 430: 31722.
  • 217
    Teyke T, Weiss KR, Kupfermann I. An identified neuron (CPR) evokes neuronal responses reflecting food arousal in Aplysia. Science 1990; 247: 857.
  • 218
    Kupfermann I. Feeding behavior in Aplysia: a simple system for the study of motivation. Behav Biol 1974; 10: 126.
  • 219
    Hurwitz I, Kupfermann I, Susswein AJ. Different roles of neurons B63 and B34 that are active during the protraction phase of buccal motor programs in Aplysia californica. J Neurophysiol 1997; 78: 130519.
  • 220
    Blumberg S, Susswein AJ. Consummatory feeding movements in Aplysia fasciata are facilitated by conspecifics with access to mates, by reproductive tract homogenates and by bag cell peptides. J Comp Physiol 1998; 182: 17582.
  • 221
    Del Parigi A, Chen K, Salbe AD, Reiman EM, Tataranni PA. Are we addicted to food? Obes Res 2003; 11: 4935.
  • 222
    Di Chiara G, Imperato A. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci U S A 1988; 85: 52748.
  • 223
    Zhou QY, Palmiter RD. Dopamine-deficient mice are severely hypoactive, adipsic, and aphagic. Cell 1995; 83: 1197209.
  • 224
    Wirshing DA. Schizophrenia and obesity: impact of antipsychotic medications. J Clin Psychiatry 2004; 65 (Suppl. 18): 1326.
  • 225
    Saper CB, Chou TC, Elmquist JK. The need to feed: homeostatic and hedonic control of eating. Neuron 2002; 36: 199211.
  • 226
    Baldo BA, Sadeghian K, Basso AM, Kelley AE. Effects of selective dopamine D1 or D2 receptor blockade within nucleus accumbens subregions on ingestive behavior and associated motor activity. Behav Brain Res 2002; 137: 16577.
  • 227
    Kelley AE. Ventral striatal control of appetitive motivation: role in ingestive behavior and reward-related learning. Neurosci Biobehav Rev 2004; 27: 76576.
  • 228
    Kelley AE, Will MJ, Steininger TL, Zhang M, Haber SN. Restricted daily consumption of a highly palatable food (chocolate Ensure(R)) alters striatal enkephalin gene expression. Eur J Neurosci 2003; 18: 25928.
  • 229
    Zhang M, Gosnell BA, Kelley AE. Intake of high-fat food is selectively enhanced by mu opioid receptor stimulation within the nucleus accumbens. J Pharmacol Exp Ther 1998; 285: 90814.
  • 230
    Will MJ, Franzblau EB, Kelley AE. The amygdala is critical for opioid-mediated binge eating of fat. Neuroreport 2004; 15: 185760.
  • 231
    Balleine BW, Killcross AS, Dickinson A. The effect of lesions of the basolateral amygdala on instrumental conditioning. J Neurosci 2003; 23: 66675.
  • 232
    Maldonado-Irizarry CS, Swanson CJ, Kelley AE. Glutamate receptors in the nucleus accumbens shell control feeding behavior via the lateral hypothalamus. J Neurosci 1995; 15: 677988.
  • 233
    Mogenson GJ, Jones DL, Yim CY. From motivation to action: functional interface between the limbic system and the motor system. Prog Neurobiol 1980; 14: 6997.
  • 234
    Risold PY, Thompson RH, Swanson LW. The structural organization of connections between hypothalamus and cerebral cortex. Brain Res Brain Res Rev 1997; 24: 197254.
  • 235
    Rolls ET. Smell, taste, texture, and temperature multimodal representations in the brain, and their relevance to the control of appetite. Nutr Rev 2004; 62: S193204; discussion: S224141.
  • 236
    Cechetto DF, Saper CB. Evidence for a viscerotopic sensory representation in the cortex and thalamus in the rat. J Comp Neurol 1987; 262: 2745.
  • 237
    Yaxley S, Rolls ET, Sienkiewicz ZJ. The responsiveness of neurons in the insular gustatory cortex of the macaque monkey is independent of hunger. Physiol Behav 1988; 42: 2239.
  • 238
    Rolls ET, Baylis LL. Gustatory, olfactory, and visual convergence within the primate orbitofrontal cortex. J Neurosci 1994; 14: 543752.
  • 239
    Kringelbach ML, O'Doherty J, Rolls ET, Andrews C. Activation of the human orbitofrontal cortex to a liquid food stimulus is correlated with its subjective pleasantness. Cereb Cortex 2003; 13: 106471.
  • 240
    Tataranni PA, Gautier JF, Chen K et al. Neuroanatomical correlates of hunger and satiation in humans using positron emission tomography. Proc Natl Acad Sci U S A 1999; 96: 456974.
  • 241
    DelParigi A, Chen K, Salbe AD, Reiman EM, Tataranni PA. Sensory experience of food and obesity: a positron emission tomography study of the brain regions affected by tasting a liquid meal after a prolonged fast. Neuroimage 2005; 24: 43643.
  • 242
    DelParigi A, Chen K, Salbe AD et al. Persistence of abnormal neural responses to a meal in postobese individuals. Int J Obes Relat Metab Disord 2004; 28: 3707.
  • 243
    Kagotani Y, Hashimoto T, Tsuruo Y, Kawano H, Daikoku S, Chihara K. Development of the neuronal system containing neuropeptide Y in the rat hypothalamus. Int J Dev Neurosci 1989; 7: 35974.
  • 244
    Grove KL, Smith MS. Ontogeny of the hypothalamic neuropeptide Y system. Physiol Behav 2003; 79: 4763.
  • 245
    Cramer CP, Blass EM. Nutritive and nonnutritive determinants of milk intake of suckling rats. Behav Neurosci 1985; 99: 57882.
  • 246
    Broberger C, Johansen J, Schalling M, Hökfelt T. Hypothalamic neurohistochemistry of the murine anorexia (anx/anx) mutation: altered processing of neuropeptide Y in the arcuate nucleus. J Comp Neurol 1997; 387: 12435.
  • 247
    Broberger C, Johansen J, Brismar H, Johansson C, Schalling M, Hökfelt T. Changes in neuropeptide Y receptors and pro-opiomelanocortin in the anorexia (anx/anx) mouse hypothalamus. J Neurosci 1999; 19: 71309.
  • 248
    Singer LK, Kuper J, Brogan RS, Smith MS, Grove KL. Novel expression of hypothalamic neuropeptide Y during postnatal development in the rat. Neuroreport 2000; 11: 107580.
  • 249
    Mistry AM, Swick A, Romsos DR. Leptin alters metabolic rates before acquisition of its anorectic effect in developing neonatal mice. Am J Physiol 1999; 277: R7427.
  • 250
    Hayashida T, Nakahara K, Mondal MS et al. Ghrelin in neonatal rats: distribution in stomach and its possible role. J Endocrinol 2002; 173: 23945.
  • 251
    Ahima RS, Prabakaran D, Flier JS. Postnatal leptin surge and regulation of circadian rhythm of leptin by feeding. Implications for energy homeostasis and neuroendocrine function. J Clin Invest 1998; 101: 10207.
  • 252
    Bouret SG, Draper SJ, Simerly RB. Trophic action of leptin on hypothalamic neurons that regulate feeding. Science 2004; 304: 10810.
  • 253
    Levin BE, Govek E. Gestational obesity accentuates obesity in obesity-prone progeny. Am J Physiol 1998; 275: R13749.
  • 254
    Dabelea D, Hanson RL, Lindsay RS et al. Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. Diabetes 2000; 49: 220811.
  • 255
    Grove KL, Williams SM, Xiao XQ, Smith MS. Fetal metabolic adaptations in nonhuman primates (NHP): effects of diet-induced gestational hyperinsulinemia and hyperleptinemia. In Endocrine Society Proceedings, San Francisco, CA, USA, 2005.
  • 256
    Gruenewald DA, Naai MA, Marck BT, Matsumoto AM. Age-related decrease in neuropeptide-Y gene expression in the arcuate nucleus of the male rat brain is independent of testicular feedback. Endocrinology 1994; 134: 23839.
  • 257
    Gruenewald DA, Matsumoto AM. Age-related decrease in proopiomelanocortin gene expression in the arcuate nucleus of the male rat brain. Neurobiol Aging 1991; 12: 11321.
  • 258
    Leal S, Andrade JP, Paula-Barbosa MM, Madeira MD. Arcuate nucleus of the hypothalamus: effects of age and sex. J Comp Neurol 1998; 401: 6588.
  • 259
    Langhans W. Anorexia of infection: current prospects. Nutrition 2000; 16: 9961005.
  • 260
    von Meyenburg C, Hrupka BH, Arsenijevic D, Schwartz GJ, Landmann R, Langhans W. Role for CD14, TLR2, and TLR4 in bacterial product-induced anorexia. Am J Physiol Regul Integr Comp Physiol 2004; 287: R298305.
  • 261
    Bret-Dibat JL, Bluthe RM, Kent S, Kelley KW, Dantzer R. Lipopolysaccharide and interleukin-1 depress food-motivated behavior in mice by a vagal-mediated mechanism. Brain Behav Immun 1995; 9: 2426.
  • 262
    Cao C, Matsumura K, Yamagata K, Watanabe Y. Induction by lipopolysaccharide of cyclooxygenase-2 mRNA in rat brain; its possible role in the febrile response. Brain Res 1995; 697: 18796.
  • 263
    Lugarini F, Hrupka BJ, Schwartz GJ, Plata-Salaman CR, Langhans W. A role for cyclooxygenase-2 in lipopolysaccharide-induced anorexia in rats. Am J Physiol Regul Integr Comp Physiol 2002; 283: R8628.
  • 264
    von Meyenburg C, Langhans W, Hrupka BJ. Evidence for a role of the 5-HT2C receptor in central lipopolysaccharide-, interleukin-1 beta-, and leptin-induced anorexia. Pharmacol Biochem Behav 2003; 74: 102531.
  • 265
    Waldbillig RJ, Bartness TJ, Stanley BG. Increased food intake, body weight, and adiposity in rats after regional neurochemical depletion of serotonin. J Comp Physiol Psychol 1981; 95: 391405.
  • 266
    Nonogaki K, Strack AM, Dallman MF, Tecott LH. Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nat Med 1998; 4: 11526.
  • 267
    Heisler LK, Cowley MA, Tecott LH et al. Activation of central melanocortin pathways by fenfluramine. Science 2002; 297: 60911.
  • 268
    Madej T, Boguski MS, Bryant SH. Threading analysis suggests that the obese gene product may be a helical cytokine. FEBS Lett 1995; 373: 138.
  • 269
    Baumann H, Morella KK, White DW et al. The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors. Proc Natl Acad Sci U S A 1996; 93: 83748.
  • 270
    Evans WK, Makuch R, Clamon GH et al. Limited impact of total parenteral nutrition on nutritional status during treatment for small cell lung cancer. Cancer Res 1985; 45: 334753.
  • 271
    Inagaki J, Rodriguez V, Bodey GP. Proceedings: causes of death in cancer patients. Cancer 1974; 33: 56873.
  • 272
    Tisdale MJ. Tumor-host interactions. J Cell Biochem 2004; 93: 8717.
  • 273
    Todorov P, Cariuk P, McDevitt T, Coles B, Fearon K, Tisdale M. Characterization of a cancer cachectic factor. Nature 1996; 379: 73942.
  • 274
    Lorite MJ, Smith HJ, Arnold JA, Morris A, Thompson MG, Tisdale MJ. Activation of ATP-ubiquitin-dependent proteolysis in skeletal muscle in vivo and murine myoblasts in vitro by a proteolysis-inducing factor (PIF). Br J Cancer 2001; 85: 297302.
  • 275
    Whitehouse AS, Smith HJ, Drake JL, Tisdale MJ. Mechanism of attenuation of skeletal muscle protein catabolism in cancer cachexia by eicosapentaenoic acid. Cancer Res 2001; 61: 36049.
  • 276
    Barber MD, Ross JA, Voss AC, Tisdale MJ, Fearon KC. The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with pancreatic cancer. Br J Cancer 1999; 81: 806.
  • 277
    Olden K, Wilson S. Environmental health and genomics: visions and implications. Nat Rev Genet 2000; 1: 14953.
  • 278
    Allison DB, Kaprio J, Korkeila M, Koskenvuo M, Neale MC, Hayakawa K. The heritability of body mass index among an international sample of monozygotic twins reared apart. Int J Obes Relat Metab Disord 1996; 20: 5016.
  • 279
    Stunkard AJ, Harris JR, Pedersen NL, McClearn GE. The body-mass index of twins who have been reared apart. N Engl J Med 1990; 322: 14837.
  • 280
    Friedman JM. A war on obesity, not the obese. Science 2003; 299: 8568.
  • 281
    Ravussin E, Bogardus C. Energy balance and weight regulation: genetics versus environment. Br J Nutr 2000; 83 (Suppl. 1): S1720.
  • 282
    Montague CT, Farooqi IS, Whitehead JP et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997; 387: 9038.
  • 283
    Clement K, Vaisse C, Lahlou N et al. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 1998; 392: 398401.
  • 284
    Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gruters A. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet 1998; 19: 1557.
  • 285
    Jackson RS, Creemers JW, Ohagi S et al. Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet 1997; 16: 3036.
  • 286
    Yeo GS, Farooqi IS, Aminian S, Halsall DJ, Stanhope RG, O'Rahilly S. A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat Genet 1998; 20: 1112.
  • 287
    Vaisse C, Clement K, Durand E, Hercberg S, Guy-Grand B, Froguel P. Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity. J Clin Invest 2000; 106: 25362.
  • 288
    Hinney A, Hohmann S, Geller F et al. Melanocortin-4 receptor gene: case-control study and transmission disequilibrium test confirm that functionally relevant mutations are compatible with a major gene effect for extreme obesity. J Clin Endocrinol Metab 2003; 88: 425867.
  • 289
    Jacobson P, Ukkola O, Rankinen T et al. Melanocortin 4 receptor sequence variations are seldom a cause of human obesity: the Swedish Obese Subjects, the HERITAGE Family Study, and a Memphis cohort. J Clin Endocrinol Metab 2002; 87: 44426.
  • 290
    Galuska DA, Will JC, Serdula MK, Ford ES. Are health care professionals advising obese patients to lose weight? JAMA 1999; 282: 15768.
  • 291
    Wee CC, McCarthy EP, Davis RB, Phillips RS. Physician counseling about exercise. JAMA 1999; 282: 15838.
  • 292
    Fong TM. Advances in anti-obesity therapeutics. Expert Opin Investig Drugs 2005; 14: 24350.
  • 293
    Raisch DW, Fye CL, Boardman KD, Sather MR. Opioid dependence treatment, including buprenorphine/naloxone. Ann Pharmacother 2002; 36: 31221.
  • 294
    Jones RM, Boatman PD, Semple G, Shin YJ, Tamura SY. Clinically validated peptides as templates for de novo peptidomimetic drug design at G-protein-coupled receptors. Curr Opin Pharmacol 2003; 3: 53043.
  • 295
    MacNeil DJ, Howard AD, Guan X et al. The role of melanocortins in body weight regulation: opportunities for the treatment of obesity. Eur J Pharmacol 2002; 450: 93109.
  • 296
    Chen RZ, Huang RR, Shen CP, MacNeil DJ, Fong TM. Synergistic effects of cannabinoid inverse agonist AM251 and opioid antagonist nalmefene on food intake in mice. Brain Res 2004; 999: 22730.
  • 297
    Beal JE, Olson R, Laubenstein L et al. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage 1995; 10: 8997.
  • 298
    Heymsfield SB, Greenberg AS, Fujioka K et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 1999; 282: 156875.
  • 299
    Montez JM, Soukas A, Asilmaz E, Fayzikhodjaeva G, Fantuzzi G, Friedman JM. Acute leptin deficiency, leptin resistance, and the physiologic response to leptin withdrawal. Proc Natl Acad Sci U S A 2005; 102: 253742.
  • 300
    Farooqi IS, Matarese G, Lord GM et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 2002; 110: 1093103.
  • 301
    Oral EA, Simha V, Ruiz E et al. Leptin-replacement therapy for lipodystrophy. N Engl J Med 2002; 346: 5708.
  • 302
    Javor ED, Ghany MG, Cochran EK et al. Leptin reverses nonalcoholic steatohepatitis in patients with severe lipodystrophy. Hepatology 2005; 41: 75360.
  • 303
    Welt CK, Chan JL, Bullen J et al. Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med 2004; 351: 98797.
  • 304
    Del Parigi A, Gautier JF, Chen K et al. Neuroimaging and obesity: mapping the brain responses to hunger and satiation in humans using positron emission tomography. Ann N Y Acad Sci 2002; 967: 38997.