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Peripheral and central signals in the control of eating in normal, obese and binge-eating human subjects

Published online by Cambridge University Press:  09 March 2007

Per M. Hellström ,
Allan Geliebter ,
Erik Näslund ,
Peter T. Schmidt ,
Eric K. Yahav ,
Sami A. Hashim  and
Martin R. Yeomans
Per M. Hellström
Affiliation:
Department of Gastroenterology and Hepatology, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden
Allan Geliebter
Affiliation:
Departments of Psychiatry and Medicine, NY Obesity Research Center, Babcock 10-A, St Luke's Roosevelt Hospital Center, Columbia University, College of Physicians and Surgeons, 1111, Amsterdam, Ave NY 10025, USA
Erik Näslund
Affiliation:
Division of Surgery, Karolinska Institutet Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden
Peter T. Schmidt
Affiliation:
Department of Gastroenterology and Hepatology, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden
Eric K. Yahav
Affiliation:
Departments of Psychiatry and Medicine, NY Obesity Research Center, Babcock 10-A, St Luke's Roosevelt Hospital Center, Columbia University, College of Physicians and Surgeons, 1111, Amsterdam, Ave NY 10025, USA
Sami A. Hashim
Affiliation:
Departments of Psychiatry and Medicine, NY Obesity Research Center, Babcock 10-A, St Luke's Roosevelt Hospital Center, Columbia University, College of Physicians and Surgeons, 1111, Amsterdam, Ave NY 10025, USA
Martin R. Yeomans*
Affiliation:
Department of Psychology, School of Life Sciences, University of Sussex, Brighton, Sussex BN1 9QG, UK
*
*Corresponding author: Dr Martin R. Yeomans, fax +44 1273 678058, email [email protected]
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Abstract

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The worldwide increase in the incidence of obesity is a consequence of a positive energy balance, with energy intake exceeding expenditure. The signalling systems that underlie appetite control are complex, and the present review highlights our current understanding of key components of these systems. The pattern of eating in obesity ranges from over-eating associated with binge-eating disorder to the absence of binge-eating. The present review also examines evidence of defects in signalling that differentiate these sub-types. The signalling network underlying hunger, satiety and metabolic status includes the hormonal signals leptin and insulin from energy stores, and cholecystokinin, glucagon-like peptide-1, ghrelin and peptide YY3-36 from the gastrointestinal tract, as well as neuronal influences via the vagus nerve from the digestive tract. This information is routed to specific nuclei of the hypothalamus and brain stem, such as the arcuate nucleus and the solitary tract nucleus respectively, which in turn activate distinct neuronal networks. Of the numerous neuropeptides in the brain, neuropeptide Y, agouti gene-related peptide and orexin stimulate appetite, while melanocortins and α-melanocortin-stimulating hormone are involved in satiety. Of the many gastrointestinal peptides, ghrelin is the only appetite-stimulating hormone, whereas cholecystokinin, glucagon-like peptide-1 and peptide YY3-36 promote satiety. Adipose tissue provides signals about energy storage levels to the brain through leptin, adiponectin and resistin. Binge-eating has been related to a dysfunction in the ghrelin signalling system. Moreover, changes in gastric capacity are observed, and as gastric capacity is increased, so satiety signals arising from gastric and post-gastric cues are reduced. Understanding the host of neuropeptides and peptide hormones through which hunger and satiety operate should lead to novel therapeutic approaches for obesity; potential therapeutic strategies are highlighted.

Keywords

Signalling systemsObesityHormones
Type
Research Article
Information
British Journal of Nutrition , Volume 92 , Issue S1 , August 2004 , pp. S47 - S57
Copyright
Copyright © The Nutrition Society 2004

References

Adam, JA, Menheere, PP, van Dielen, FM, Soeters, PB, Buurman, WA & Greve, JW (2002) Decreased plasma orexin-A levels in obese individuals. Int J Obes Relat Metab Disord 26, 274–276.CrossRefGoogle ScholarPubMed
Adami, GF, Meneghelli, A & Scopinaro, N (1999) Night eating and binge-eating disorder in obese patients. Int J Eat Disord 25, 335–338.3.0.CO;2-1>CrossRefGoogle ScholarPubMed
Asakawa, A, Inui, A, Kaga, T, Yuzuriha, H, Nagata, T, Fujimiya, M, Katsuura, G, Makino, S, Fujino, MA & Kasuga, M (2001) A role of ghrelin in neuroendocrine and behavioral responses to stress in mice. Neuroendocrinology 74, 143–147.CrossRefGoogle ScholarPubMed
Ballinger, A, McLoughlin, L, Medback, S & Clark, M (1995) Cholecystokinin is a satiety hormone in humans at physiological concentrations. Clin Sci 89, 375–381.CrossRefGoogle Scholar
Batterham, RL (2002) Gut hormone PYY3-36 physiologically inhibits food intake. Nature 418, 650–654.CrossRefGoogle Scholar
Batterham, RL, Cohen, MA, Ellis, SM, Le Roux, CW, Withers, DJ, Frost, GS, Ghatei, MA & Bloom, SR (2003) Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med 349, 941–948.CrossRefGoogle ScholarPubMed
Batterham, RL, Cowley, MA, Small, CJ, et al. (2002) Gut hormone PYY(3-36) physiologically inhibits food intake. Nature 418, 650–654.CrossRefGoogle ScholarPubMed
Bell, GI, Santerre, RF & Mullenbach, GT (1983) Hamster preproglucagon contains the sequence of glucagon and two related peptides. Nature 302, 716–718.CrossRefGoogle ScholarPubMed
Berg, AH, Combs, TP & Scherer, PE (2002) ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab 13, 84–89.CrossRefGoogle ScholarPubMed
Bloom, SR (1997) Glucagon-like peptide-1 and satiety. Nature 385, 214.CrossRefGoogle Scholar
Branson, R, Potoczna, N, Kral, JG, Lentes, KU, Hoehe, MR & Horber, FF (2003) Binge eating as a major phenotype of melanocortin 4 receptor gene mutations. N Engl J Med 348, 1096–1103.CrossRefGoogle Scholar
Bray, GA (2000) Afferent signals regulating food intake. Proc Nutr Soc 59, 373–384.CrossRefGoogle ScholarPubMed
Broberger, C, Holmberg, K, Kuhar, MJ & Hokfelt, T (1999) Cocaine- and amphetamine-regulated transcript in the rat vagus nerve: a putative mediator of cholecystokinin-induced satiety. Proc Natl Acad Sci USA 96, 13506–13511.CrossRefGoogle ScholarPubMed
Broberger, C, Johansen, J, Johansson, C, Schalling, M & Hokfelt, T (1998) The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice. Proc Natl Acad Sci USA 95, 15043–15048.CrossRefGoogle ScholarPubMed
Brolin, RE (1992) Critical analysis of results: weight loss and quality of data. Am J Clin Nutr 55, 577S–581S.CrossRefGoogle ScholarPubMed
Buchan, AM, Polak, JM, Solcia, E, Capella, C, Hudson, D & Pearse, AG (1978) Electron immunohistochemical evidence for human intestinal I cells as the source of CCK. Gut 19, 403–407.CrossRefGoogle Scholar
Burdyga, G, Lal, S, Spiller, D, et al. (2003) Localization of orexin-1 receptors to vagal afferent neurons in the rat and humans. Gastroenterology 124, 129–139.CrossRefGoogle ScholarPubMed
Chamorro, S, Della-Zuana, O, Fauchere, JL, Feletou, M, Galizzi, JP & Levens, N (2002) Appetite suppression based on selective inhibition of NPY receptors. Int J Obes Relat Metab Disord 26, 281–298.CrossRefGoogle ScholarPubMed
Clement, K, Dina, C, Basdevant, A, Chastang, N, Pelloux, V, Lahlou, N, Berlan, M, Langin, D, Guy-Grand, B & Froguel, P (1999) A sib-pair analysis study of 15 candidate genes in French families with morbid obesity: indication for linkage with islet 1 locus on chromosome 5q. Diabetes 48, 398–402.CrossRefGoogle ScholarPubMed
Cummings, DE & Foster, KE (2003) Ghrelin–leptin tango in body-weight regulation. Gastroenterology 124, 1532–1535.CrossRefGoogle ScholarPubMed
Cummings, DE, Purnell, JQ, Frayo, RS, Schmidova, K, Wisse, BE & Weigle, DS (2001) A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 50, 1714–1719.CrossRefGoogle ScholarPubMed
De Zwaan, M, Mitchell, JE, Raymond, NC & Spitzer, RL (1994) Binge eating disorder: clinical features and treatment of a new diagnosis. Harv Rev Psychiatry 1, 310–325.CrossRefGoogle ScholarPubMed
Flegal, KM, Carroll, MD, Ogden, CL & Johnson, CL (2002) Prevalence and trends in obesity among US adults, 1999–2000. J Am Med Assoc 288, 1723–1727.CrossRefGoogle ScholarPubMed
Flint, A, Raben, A, Astrup, A & Holst, JJ (1998) Glucagon-like peptide-1 promotes satiety and suppresses energy intake in humans. J Clin Invest 101, 515–520.CrossRefGoogle ScholarPubMed
Flint, A, Raben, A, Rehfeld, JF, Holst, JJ & Astrup, A (2000) The effect of glucagon-like peptide-1 on energy expenditure and substrate metabolism in humans. Int J Obes 24, 288–298.CrossRefGoogle ScholarPubMed
French, SJ, Murray, B, Rumsey, RD, Sepple, CP & Read, NW (1993) Is cholecystokinin a satiety hormone? Correlations of plasma cholecystokinin with hunger, satiety and gastric emptying in normal volunteers. Appetite 21, 95–104.CrossRefGoogle ScholarPubMed
Fuxe, K, Tinner, B, Caberlotto, L, Bunnemann, B & Agnati, L (1997) NPY Y1 receptor-like immunoreactivity exists in a subpopulation of β-endorphin immunoreactive nerve cells in the arcuate nucleus: a double immunolabelling analysis in the rat. Neurosci Lett 225, 49–52.CrossRefGoogle Scholar
Geliebter, A (1988) Gastric distension and gastric capacity in relation to food intake in humans. Physiol Behav 44, 665–668.CrossRefGoogle ScholarPubMed
Geliebter, A (2002) Weight loss and plasma ghrelin levels. N Engl J Med 347, 1379–1381.Google ScholarPubMed
Geliebter, A & Hashim, SA (2001) Gastric capacity in normal, obese, and bulimic women. Physiol Behav 74, 743–746.CrossRefGoogle ScholarPubMed
Geliebter, A, Melton, PM, McCray, RS, Gallagher, DR, Gage, D & Hashim, SA (1992) Gastric capacity, gastric emptying, and test-meal intake in normal and bulimic women. Am J Clin Nutr 56, 656–661.CrossRefGoogle ScholarPubMed
Geliebter, A, Westreich, S, Pierson, RN & Van Itallie, TB (1986) Extra-abdominal pressure alters food intake, intragastric pressure, and gastric emptying rate. Am J Physiol 250, R549–R552.Google ScholarPubMed
Geliebter, A, Yahav, E, Gluck, M & Hashim, SA (2004) Gastric capacity, test meal intake, and appetitive hormones in binge-eating disorder. Physiol Behav (In Press).Google Scholar
Geracioti, TD & Liddle, RA (1988) Impaired cholecystokinin secretion in bulimia nervosa. N Engl J Med 319, 683–688.CrossRefGoogle ScholarPubMed
Grill, HJ & Norgren, R (1978) Chronically decerebrate rats demonstrate satiation but not bait-shyness. Science 201, 267–269.CrossRefGoogle Scholar
Gutzwiller, JP, Drewe, J, Göke, BSchmidt, H, Rohrer, B, Lareida, J & Beglinger, C (1999a) Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitustype 2. Am J Physiol 276, R1541–R1544.Google Scholar
Gutzwiller, JP, Göke, B, Drewe, J, Hildebrand, P, Ketterer, S, Handschin, D, Winterhalder, R, Conen, D & Beglinger, C (1999b) Glucagon-like peptide-1: a potent regulator of food intake in humans. Gut 44, 81–86.CrossRefGoogle ScholarPubMed
Hagan, MM (2002) PeptideYY: a key mediator of orexigenic behavior. Peptides 23, 377–382.CrossRefGoogle Scholar
Hagan, MM, Rushing, PA, Pritchard, LM, Schwartz, MW, Strack, AM, Van Der Ploeg, LH, Woods, SC & Seeley, RJ (2000) Long-term orexigenic effects of AgRP-(831-32) involve mechanisms other than melanocortin receptor blockade. Am J Physiol Regul Integr Comp Physiol 279, R47–R52.CrossRefGoogle Scholar
Hahn, TM, Breininger, JF, Baskin, DG & Schwartz, MW (1998) Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons. Nat Neurosci 1, 271–272.CrossRefGoogle ScholarPubMed
Hewson, G, Leighton, RG & Hughes, J (1988) The cholecystokinin receptor antagonist L364,718 increases food intake in the rat by attenuation of the action of endogenous cholecystokinin. Br J Pharmacol 93, 79–84.CrossRefGoogle ScholarPubMed
Heymsfield, SB, Greenberg, AS, Fujioka, K, et al. (1999) Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. J Am Med Assoc 282, 1568–1575.CrossRefGoogle ScholarPubMed
Hill, JO & Peters, JC (1998) Environmental contributions to the obesity epidemic. Science 280, 1371–1374.CrossRefGoogle Scholar
Holst, JJ (1997) Enteroglucagon. Annu Rev Physiol 59, 257–271.CrossRefGoogle ScholarPubMed
Hotta, K, Funahashi, T & Arita, Y (2000) Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 20, 1595–1599.CrossRefGoogle ScholarPubMed
Hu, E, Liang, P & Spiegelman, BM (1996) AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 271, 10697–10703.CrossRefGoogle ScholarPubMed
Hug, C & Lodish, HF (2002) Diabetes, obesity, and Acrp30/adiponectin. Biotechniques 33, 654–656 658 passim.CrossRefGoogle ScholarPubMed
Imeryuz, N, Yegen, BC, Bozkurt, A, Coskun, T, Villanueva-Penacarrillo, ML & Ulusoy, NB (1997) Glucagon-like peptide-1 inhibits gastric emptying via vagal afferent-mediated central mechanisms. Am J Physiol 273, G920–G927.Google ScholarPubMed
Jin, SL, Han, VK, Simmons, JG, Towle, AC, Lauder, JM & Lund, PK (1988) Distribution of glucagonlike peptide I (GLP-I), glucagon, and glicentin in the rat brain: an immunocytochemical study. J Comp Neurol 271, 519–532.CrossRefGoogle Scholar
Kersten, S, Mandard, S, Tan, NS, Escher, P, Metzger, D, Chambon, P, Gonzalez, FJ, Desvergne, B & Wahli, W (2000) Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene. J Biol Chem 275, 28488–28493.CrossRefGoogle ScholarPubMed
Kim, I, Kim, HG, Kim, H, Kim, HH, Park, SK, Uhm, CS, Lee, ZH & Koh, GY (2000) Hepatic expression, synthesis and secretion of a novel fibrinogen/angiopoietin-related protein that prevents endothelial-cell apoptosis. Biochem J, 346, 603–610.CrossRefGoogle ScholarPubMed
Kirchgessner, AL (2002) Orexins in the brain–gut axis. Endocrol Rev 23, 1–15.CrossRefGoogle ScholarPubMed
Kirchgessner, AL & Liu, M (1999) Orexin synthesis and response in the gut. Neuron 24, 941–951.CrossRefGoogle ScholarPubMed
Kissileff, HR, Pi-Sunyer, FX, Thornton, J & Smith, GP (1981) C-terminal octapeptide of cholecystokinin decreases food intake in man. Am J Clin Nutr 34, 154–160.CrossRefGoogle ScholarPubMed
Kojima, M, Hosoda, H, Date, Y, Nakazato, M, Matsuo, H & Kangawa, K (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402, 656–660.CrossRefGoogle ScholarPubMed
Komaki, G, Matsumoto, Y, Nishikata, H, Kawai, K, Nozaki, T, Takii, M, Sogawa, H & Kubo, C (2001) Orexin-A and leptin change inversely in fasting non-obese subjects. Eur J Endocrinol 144, 645–651.CrossRefGoogle ScholarPubMed
Kreymann, B, Ghatei, MA, Burnet, P, Williams, G, Kanse, S, Diani, AR & Bloom, SR (1989) Characterization of glucagon-like peptide-1-(73-6)amide in the hypothalamus. Brain Res 502, 325–331.CrossRefGoogle Scholar
Lambert, PD, Wilding, PH, Ghatei, MA & Bloom, SR (1994) A role for GLP-1-(73-6)NH2 in the central control of feeding behaviour. Digestion 54, 360–361.Google Scholar
Lieverse, RJ, Jansen, JBMJ, Zwan, A, Samson, L, Masclee, AAM & Lamers, CBHW (1993) Satiety effects of a physiological dose of cholecystokinin in humans. Gut 36, 176–179.CrossRefGoogle Scholar
Londos, C, Gruia-Gray, J, Brasaemle, DL, Rondinone, CM, Takeda, T, Dwyer, NK, Barber, T, Kimmel, AR & Blanchette-Mackie, EJ (1996) Perilipin: possible roles in structure and metabolism of intracellular neutral lipids in adipocytes and steroidogenic cells. Int J Obes Relat Metab Disord 20, Suppl. 3S97–S101.Google ScholarPubMed
Long, SJ, Sutton, JA, Amaee, WB, Giouvanoudi, A, Spyrou, NM, Rogers, PJ & Morgan, LV (1999) No effect of glucagon-like peptide-1 on short-term satiety and energy intake in man. Br J Nutr 81, 273–279.CrossRefGoogle ScholarPubMed
Lovshin, J & Drucker, DJ (2000) New frontiers in the biology of GLP-2. Regul Pept 90, 27–32.CrossRefGoogle ScholarPubMed
Mac Dougald, OA & Mandrup, S (2002) Adipogenesis: forces that tip the scales. Trends Endocrinol Metab 13, 5–11.CrossRefGoogle ScholarPubMed
Matsubara, M, Maruoka, S & Katayose, S (2002) Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women. Eur J Endocrinol 147, 173–180.CrossRefGoogle ScholarPubMed
Mercer, JG & Lawrence, CB (1992) Selectivity of cholecystokinin (CCK) receptor antagonists, MK-329 and L-365,260, for axonally-transported CCK binding sites on the rat vagus nerve. Neurosci Lett 137, 229–231.CrossRefGoogle ScholarPubMed
Morley, JE, Levine, AS, Grace, M & Kneip, J (1985) Peptide YY, (PYY), a potent orexigenic agent. Brain Res 341, 200–203.CrossRefGoogle ScholarPubMed
Nakazato, M, Murakami, N, Date, Y, Kojima, M, Matsuo, H, Kangawa, K & Matsukura, S (2001) A role for ghrelin in the central regulation of feeding. Nature 409, 194–198.CrossRefGoogle ScholarPubMed
Näslund, E, Barkeling, B, King, N, Gutniak, M, Blundell, JE, Holst, JJ, Rössner, S, Hellström, PM (1999a) Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in obese men. Int J Obes Relat Metab Disord 23, 304–311.CrossRefGoogle ScholarPubMed
Näslund, E, Bogefors, J, Skogar, S, Grybäck, P, Jacobsson, H, Holst, JJ, Hellström, PM (1999b) GLP-1 slows solid gastric emptying and inhibits insulin, glucagon, and PYY release in humans. Am J Physiol 277, R910–R916.Google ScholarPubMed
Näslund, E, Ehrström, M, Ma, J, Hellström, PM & Kirchgessner, AL (2002) Localization and effects of orexin on fasting motility in the rat duodenum. Am J Physiol 282, G470–G479.Google ScholarPubMed
Näslund, E, Grybäck, P, Backman, L, Jacobsson, H, Holst, JJ, Theo-dorsson, E, Hellström, PM (1998a) Distal small bowel hormones: correlation with fasting antroduodenal motility and gastric emptying. Dig Dis Sci 43, 945–952.CrossRefGoogle ScholarPubMed
Näslund, E, Gutniak, M, Skogar, S, Rossner, S & Hellström, PM (1998b) Glucagon-like peptide 1 increases the period of postprandial satiety and slows gastric emptying in obese men. Am J Clin Nutr 68, 525–530.CrossRefGoogle ScholarPubMed
Näslund, E, King, N, Mansten, S, Adner, S, Holst, JJ, Gutniak, M & Hellström, PM (2004) Prandial subcutaneous injuctions of glucagon-like peptide-1 cause weight loss in obsess human subjects. Br J Nutr 91, 439–446.CrossRefGoogle Scholar
Nauck, MA, Niedereichholz, U, Ettler, R, Holst, JJÖrskov, CRitzel, R & Schmiegel, WH (1997) Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol 273, E981–E988.Google ScholarPubMed
Nowak, KW, Mackowiak, P, Switonska, MM, Fabis, M & Malendowicz, LK (2000) Acute orexin effects on insulin secretion in the rat: in vivo and in vitro studies. Life Sci 66, 449–454.CrossRefGoogle ScholarPubMed
O'Rahilly, S (2003) Leptin: defining its role in humans by the clinical study of genetic disorders. Nutr Rev 60, 30–34.CrossRefGoogle Scholar
Ørskov, C (1992) Glucagon-like peptide-1, a new hormone of the enteroinsular axis. Diabetologia 35, 701–711.CrossRefGoogle Scholar
Otto, B, Cuntz, U, Fruehauf, E, Wawarta, R, Folwaczny, C, Riepl, RL, Heiman, ML, Lehnert, P, Fichter, M & Tschop, M (2001) Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. Eur J Endocrinol 145, 669–673.CrossRefGoogle ScholarPubMed
Ouedraogo, R, Näslund, E & Kirchgessner, AL (2003) Glucose regulates the release of orexin-a from the endocrine pancreas. Diabetes 52, 111–117.CrossRefGoogle ScholarPubMed
Pajvani, UB, Du, X, Combs, TP, Berg, AH, Rajala, MW, Schulthess, T, Engel, J, Brownlee, M & Scherer, PE (2003) Structure–function studies of the adipocyte-secreted hormone Acrp30/adiponectin. Implications for metabolic regulation and bioactivity. J Biol Chem 278, 9073–9085.CrossRefGoogle ScholarPubMed
Poeschla, B, Gibbs, J, Simansky, KJ, Greenberg, D & Smith, GP (1993) Cholecystokinin-induced satiety depends on activation of 5-HT1C receptors. Am J Physiol 264, R62–R64.Google Scholar
Porte, D, Baskin, DG & Schwartz, MW (2002) Leptin and insulin action in the central nervous system. Nutr Rev 60, S20–S29.CrossRefGoogle ScholarPubMed
Ranganath, L, Norris, F, Morgan, L, Wright, J & Marks, V (1999) Inhibition of carbohydrate-mediated glucagon-like peptide-1 (73-6)amide secretion by circulating non-esterified fatty acids. Clin Sci 96, 335–342.CrossRefGoogle Scholar
Ranganath, LR, Beety, JM, Morgan, LM, Wright, JW, Howland, R & Marks, V (1996) Attenuated GLP-1 secretion in obesity: cause or consequence. Gut 38, 916–919.CrossRefGoogle ScholarPubMed
Raybould, HE (1998) Does your gut taste? Sensory transduction in the gastrointestinal tract. News Physiol Sci 13, 275–280.Google ScholarPubMed
Read, N, French, SA & Cunningham, K (1994) The role of the gut in regulating food intake in man. Nutr Rev 52, 1–10.CrossRefGoogle ScholarPubMed
Reidelberger, RD, Varga, G & Solomon, TE (1991) Effects of selective cholecystokinin antagonists L364,718 and L365,260 on food intake in rats. Peptides 12, 1215–1221.CrossRefGoogle ScholarPubMed
Reubi, JC, Waser, B, Laderach, U, Stettler, C, Friess, H, Halter, F & Schmassmann, A (1997) Localization of cholecystokinin A and cholecystokinin B-gastrin receptors in the human stomach. Gastroenterology 112, 1197–1205.CrossRefGoogle ScholarPubMed
Ritter, RC, Covasa, M & Matson, CA (1999) Cholecystokinin: proofs and prospects for involvement in control of food intake and body weight. Neuropeptides 33, 387–399.CrossRefGoogle ScholarPubMed
Sakurai, T, Amemiya, A, Ishii, M, et al. (1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92, 573–585.CrossRefGoogle Scholar
Sanaka, M, Koike, Y, Yamamoto, T, Mineshita, S, Yamaoka, S, Hirama, S, Tanaka, H, Kuyama, Y & Yamanaka, M (1997) A reliable and convenient parameter of the rate of paracetamol absorption to measure gastric emptying rate of liquids. Int J Clin Pharmacol Ther 35, 509–513.Google ScholarPubMed
Sanaka, M, Kuyama, Y & Yamanaka, M (1998) Guide for judicious use of the paracetamol absorption technique in a study of gastric emptying rate of liquids. J Gastroenterol 33, 785–791.CrossRefGoogle Scholar
Scherer, PE, Williams, S, Fogliano, M, Baldini, G & Lodish, HF (1995) A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 270, 26746–26749.CrossRefGoogle ScholarPubMed
Schmidt, PT, Näslund, EGrybäck, PJacobsson, H, Hartmann, B, Holst, JJ, Hellström, PM (2003) Peripheral administration of GLP-2 to humans has no effect on gastric emptying or satiety. Regul Pept 116, 21–25.CrossRefGoogle ScholarPubMed
Schwartz, GJ, McHugh, PR & Moran, TH (1993) Gastric loads and cholecystokinin synergistically stimulate rat gastric vagal afferents. Am J Physiol 265, R872–R876.Google ScholarPubMed
Shapiro, L & Scherer, PE (1998) The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor. Curr Biol 8, 335–338.CrossRefGoogle ScholarPubMed
Shiiya, T, Nakazato, M, Mizuta, M, Date, Y, Mondal, MS, Tanaka, M, Nozoe, S, Hosoda, H, Kangawa, K & Matsukura, S (2002) Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab 87, 240–244.CrossRefGoogle ScholarPubMed
Shimizu, I, Hirota, M, Ohboshi, C & Shima, K (1987) Identification and localization of glucagon-like peptide-1 and its receptor in rat brain. Endocrinology 121, 1076–1082.CrossRefGoogle ScholarPubMed
Sobhani, I, Bado, A & Vissuzaine, C (2000) Leptin secretion and leptin receptor in the human stomach. Gut 47, 178–183.CrossRefGoogle ScholarPubMed
Sobhani, I, Buyse, M, Goiot, H, Weber, N, Laigneau, JP, Henin, D, Soul, JC & Bado, A (2002) Vagal stimulation rapidly increases leptin secretion in human stomach. Gastroenterology 122, 259–263.CrossRefGoogle ScholarPubMed
Sørensen, LB, Flint, A, Raben, A, Hartmann, B, Holst, JJ & Astrup, A (2003) No effect of physiological concentrations of glucagon-like peptide-2 on appetite and energy intake in normal weight subjects. Int J Obes 27, 450–456.CrossRefGoogle ScholarPubMed
Stellar, E (1954) The physiology of motivation. Psychol Rev 61, 5–22.CrossRefGoogle ScholarPubMed
Steppan, CM, Bailey, ST, Bhat, S, Brown, EJ, Banerjee, RR, Wright, CM, Patel, HR, Ahima, RS & Lazar, MA (2001) The hormone resistin links obesity to diabetes. Nature 409, 307–312.CrossRefGoogle ScholarPubMed
Takaya, K, Ariyasu, H & Kanamoto, N (2000) Ghrelin strongly stimulates growth hormone release in humans. J Clin Endocrinol Metab 85, 4908–4911.CrossRefGoogle ScholarPubMed
Tang-Christensen, M, Larsen, PJ, Göke, RFink-Jensen, A, Jessop, DS, Moller, M & Sheikh, SP (1996) Central administration of GLP-1-(7-36) amide inhibits food and water intake in rats. Am J Physiol 271, R848–R856.Google ScholarPubMed
Tang-Christensen, M, Larsen, PJ, Thulesen, J, Romer, J & Vrang, N (2000) The proglucagon-derived peptide, glucagon-like peptide-2, is a neurotransmitter involved in the regulation of food intake. Nat Med 6, 802–807.CrossRefGoogle ScholarPubMed
Tansey, JT, Sztalryd, C, Gruia-Gray, J, et al. (2001) Perilipin ablation results in a lean mouse with aberrant adipocyte lipolysis, enhanced leptin production, and resistance to diet-induced obesity. Proc Natl Acad Sci USA 98, 6494–6499.CrossRefGoogle Scholar
Toft-Nielsen, MB, Madsbad, S & Holst, JJ (1999) Continuous subcutaneous infusion of glucagon-like peptide-1 lowers plasma glucose and reduces appetite in type 2 diabetic patients. Diabetes Care 22, 1137–1143.CrossRefGoogle ScholarPubMed
Tolessa, T, Gutniak, M, Holst, JJ, Efendic, S & Hellström, PM (1998) Glucagon-like peptide-1 retards gastric emptying and small bowel transit in the rat: effect mediated through central or enteric nervous mechanisms. Dig Dis Sci 43, 2284–2290.CrossRefGoogle ScholarPubMed
Trayhurn, P & Beattie, JH (2001) Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proc Nutr Soc 60, 329–339.CrossRefGoogle ScholarPubMed
Tsai, CH, Hill, M & Drucker, DJ (1997) Biological determinants of intestinotrophic properties of GLP-2. Am J Physiol 272, G662–G668.Google ScholarPubMed
Tsao, TS, Lodish, HF & Fruebis, J (2002) ACRP30, a new hormone controlling fat and glucose metabolism. Eur J Pharmacol 440, 213–221.CrossRefGoogle ScholarPubMed
Tschop, M, Smiley, DL & Heiman, ML (2000) Ghrelin induces adiposity in rodents. Nature 407, 908–913.CrossRefGoogle ScholarPubMed
Tschop, M, Weyer, C, Tataranni, PA, Devanarayan, V, Ravussin, E & Heiman, ML (2001) Circulating ghrelin levels are decreased in human obesity. Diabetes 50, 707–709.CrossRefGoogle ScholarPubMed
Turton, MD, O'Shea, D & Gunn, I (1996) A role for glucagon-like peptide-1 in the central regulation of feeding. Nature 379, 69–72.CrossRefGoogle ScholarPubMed
Ukkola, O & Santaniemi, M (2002) Adiponectin: a link between excess adiposity and associated comorbidities? J Mol Med 80, 696–702.CrossRefGoogle ScholarPubMed
Wettergren, A, Schjoldager, B, Mortensen, PE, Myhre, J, Christiansen, J & Holst, JJ (1993) Truncated GLP-1 (proglucagon 781-07-amide) inhibits gastric and pancreatic functions in man. Dig Dis Sci 38, 665–673.CrossRefGoogle ScholarPubMed
Wettergren, A, Wøjdemann, M & Holst, JJ (1998) Glucagon-like peptide-1 inhibits gastropancreatic function by inhibiting central parasympathetic outflow. Am J Physiol 275, G984–G992.Google ScholarPubMed
Wettergren, A, Wøjdemann, M, Meisner, S, Stadil, F & Holst, JJ (1997) The inhibitory effect of glucagon-like peptide-1 (GLP-1) 7-36 amide on gastric acid secretion in humans depends on an intact vagal innervation. Gut 40, 597–601.CrossRefGoogle Scholar
Wikberg, JE, Muceniece, R, Mandrika, I, Prusis, P, Lindblom, J, Post, C & Skottner, A (2000) New aspects on the melanocortins and their receptors. Pharmacol Res 42, 393–420.CrossRefGoogle ScholarPubMed
Wøjdemann, M, Wettergren, A, Hartmann, B & Holst, JJ (1998) Glucagon-like peptide-2 inhibits centrally induced antral motility in pigs. Scand J Gastroenterol 33, 828–832.Google ScholarPubMed
Wren, AM, Seal, LJ, Cohen, MA, Brynes, AE, Frost, GS, Murphy, KG, Dhillo, WS, Ghatei, MA & Bloom, SR (2001) Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 86, 5992CrossRefGoogle ScholarPubMed
Yanovski, SZ (1993) Binge eating disorder: current knowledge and future directions. Obes Res 1, 306–324.Google ScholarPubMed
Yanovski, SZ (1995) Biological correlates of binge-eating. Addict Behav 20, 705–712.CrossRefGoogle ScholarPubMed
Yeo, GS, Farooqi, IS, Aminian, S, Halsall, DJ, Stanhope, RG & O'Rahilly, S (1998) A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat Genet 20, 111–112.CrossRefGoogle ScholarPubMed
Zhang, Y, Proenca, R, Maffei, M, Barone, M, Leopold, L & Friedman, JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432.CrossRefGoogle ScholarPubMed