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Endocrine Reviews 20 (1): 68-100
Copyright © 1999 by The Endocrine Society

Interacting Appetite-Regulating Pathways in the Hypothalamic Regulation of Body Weight1

Satya P. Kalra, Michael G. Dube, Shuye Pu, Bin Xu, Tamas L. Horvath and Pushpa S. Kalra

Department of Neuroscience (S.P.K., S.P., B.X.), Department of Physiology (M.G.D., P.S.K.), and The University of Florida Brain Institute, University of Florida College of Medicine, Gainesville, Florida 32610; and Department of Obstetrics and Gynecology (T.L.H.), Yale University School of Medicine, New Haven, Connecticut 06510

I. Introduction
II. Neuroanatomical Substrate for Appetite Regulation
A. Arcuate nucleus
B. Ventromedial nucleus and lateral hypothalamus
C. Dorsomedial nucleus
D. Paraventricular nucleus and perifornical hypothalamus
E. Suprachiasmatic nucleus and the timing device
F. Overview of the neuroanatomical substrate associated with appetite control
III. Orexigenic Signals
A. Neuropeptide Y
B. Galanin
C. Endogenous opioid peptides
D. Melanin-concentrating hormone
E. Amino acids: glutamate and {gamma}-aminobutyric acid
F. Hypocretins/orexins
G. Morphological and functional links among orexigenic signals
IV. Anorexigenic Signals
A. Corticotropin-releasing hormone family of peptides
B. Neurotensin
C. Glucagon-like peptide-1
D. Melanocortin and agouti protein
E. Cocaine and amphetamine-regulated transcript
V. Leptin
A. An adipocyte signal
B. Site of action
C. Is leptin a physiological satiety signal?
D. Leptin signal transduction and leptin resistance
VI. Summary




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C. B. Kaelin, A. W. Xu, X.-Y. Lu, and G. S. Barsh
Transcriptional Regulation of Agouti-Related Protein (Agrp) in Transgenic Mice
Endocrinology, December 1, 2004; 145(12): 5798 - 5806.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
M. Felies, S. von Horsten, R. Pabst, and H. Nave
Neuropeptide Y stabilizes body temperature and prevents hypotension in endotoxaemic rats
J. Physiol., November 15, 2004; 561(1): 245 - 252.
[Abstract] [Full Text] [PDF]

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 J EndocrinolHome page
G Tulipano, A V Vergoni, D Soldi, E E Muller, and D Cocchi
Characterization of the resistance to the anorectic and endocrine effects of leptin in obesity-prone and obesity-resistant rats fed a high-fat diet
J. Endocrinol., November 1, 2004; 183(2): 289 - 298.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
J. Chen and H. S. Randeva
Genomic Organization of Mouse Orexin Receptors: Characterization of Two Novel Tissue-Specific Splice Variants
Mol. Endocrinol., November 1, 2004; 18(11): 2790 - 2804.
[Abstract] [Full Text] [PDF]

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 DiabetesHome page
X. Fioramonti, A. Lorsignol, A. Taupignon, and L. Penicaud
A New ATP-Sensitive K+ Channel-Independent Mechanism Is Involved in Glucose-Excited Neurons of Mouse Arcuate Nucleus
Diabetes, November 1, 2004; 53(11): 2767 - 2775.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
W. M. Kong, N. M. Martin, K. L. Smith, J. V. Gardiner, I. P. Connoley, D. A. Stephens, W. S. Dhillo, M. A. Ghatei, C. J. Small, and S. R. Bloom
Triiodothyronine Stimulates Food Intake via the Hypothalamic Ventromedial Nucleus Independent of Changes in Energy Expenditure
Endocrinology, November 1, 2004; 145(11): 5252 - 5258.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
J. W. Bullen Jr, M. Ziotopoulou, L. Ungsunan, J. Misra, I. Alevizos, E. Kokkotou, E. Maratos-Flier, G. Stephanopoulos, and C. S. Mantzoros
Short-term resistance to diet-induced obesity in A/J mice is not associated with regulation of hypothalamic neuropeptides
Am J Physiol Endocrinol Metab, October 1, 2004; 287(4): E662 - E670.
[Abstract] [Full Text] [PDF]

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 DiabetesHome page
A. M. van den Hoek, P. J. Voshol, B. N. Karnekamp, R. M. Buijs, J. A. Romijn, L. M. Havekes, and H. Pijl
Intracerebroventricular Neuropeptide Y Infusion Precludes Inhibition of Glucose and VLDL Production by Insulin
Diabetes, October 1, 2004; 53(10): 2529 - 2534.
[Abstract] [Full Text] [PDF]

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 DiabetesHome page
R. Nogueiras, S. Tovar, S. E. Mitchell, D. V. Rayner, Z. A. Archer, C. Dieguez, and L. M. Williams
Regulation of Growth Hormone Secretagogue Receptor Gene Expression in the Arcuate Nuclei of the Rat by Leptin and Ghrelin
Diabetes, October 1, 2004; 53(10): 2552 - 2558.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
N. Ueno, M. G. Dube, A. Inui, P. S. Kalra, and S. P. Kalra
Leptin Modulates Orexigenic Effects of Ghrelin and Attenuates Adiponectin and Insulin Levels and Selectively the Dark-Phase Feeding as Revealed by Central Leptin Gene Therapy
Endocrinology, September 1, 2004; 145(9): 4176 - 4184.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
C. Perrin, C. Knauf, and R. Burcelin
Intracerebroventricular Infusion of Glucose, Insulin, and the Adenosine Monophosphate-Activated Kinase Activator, 5-Aminoimidazole-4-Carboxamide-1-{beta}-D-Ribofuranoside, Controls Muscle Glycogen Synthesis
Endocrinology, September 1, 2004; 145(9): 4025 - 4033.
[Abstract] [Full Text] [PDF]

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 Exp PhysiolHome page
K.G. Murphy and S.R. Bloom
Gut hormones in the control of appetite
Exp Physiol, September 1, 2004; 89(5): 507 - 516.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
T. Karl, S. Lin, C. Schwarzer, A. Sainsbury, M. Couzens, W. Wittmann, D. Boey, S. von Horsten, and H. Herzog
Y1 receptors regulate aggressive behavior by modulating serotonin pathways
PNAS, August 24, 2004; 101(34): 12742 - 12747.
[Abstract] [Full Text] [PDF]

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 NeuroscientistHome page
D. Burdakov
Electrical Signaling in Central Orexin/Hypocretin Circuits: Tuning Arousal and Appetite to Fit the Environment
Neuroscientist, August 1, 2004; 10(4): 286 - 291.
[Abstract] [PDF]

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 J. Pharmacol. Exp. Ther.Home page
N. Yasuda, T. Inoue, T. Nagakura, K. Yamazaki, K. Kira, T. Saeki, and I. Tanaka
Metformin Causes Reduction of Food Intake and Body Weight Gain and Improvement of Glucose Intolerance in Combination with Dipeptidyl Peptidase IV Inhibitor in Zucker fa/fa Rats
J. Pharmacol. Exp. Ther., August 1, 2004; 310(2): 614 - 619.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
J. D. Coppola, B. A. Horwitz, J. Hamilton, and R. B. McDonald
Expression of NPY Y1 and Y5 receptors in the hypothalamic paraventricular nucleus of aged Fischer 344 rats
Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2004; 287(1): R69 - R75.
[Abstract] [Full Text] [PDF]

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 Endocr. Rev.Home page
A. J. van der Lely, M. Tschop, M. L. Heiman, and E. Ghigo
Biological, Physiological, Pathophysiological, and Pharmacological Aspects of Ghrelin
Endocr. Rev., June 1, 2004; 25(3): 426 - 457.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
J. Erdmann, R. Topsch, F. Lippl, P. Gussmann, and V. Schusdziarra
Postprandial Response of Plasma Ghrelin Levels to Various Test Meals in Relation to Food Intake, Plasma Insulin, and Glucose
J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 3048 - 3054.
[Abstract] [Full Text] [PDF]

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 NeuroscientistHome page
T. L. Horvath, S. Diano, and M. Tschop
Brain Circuits Regulating Energy Homeostasis
Neuroscientist, June 1, 2004; 10(3): 235 - 246.
[Abstract] [PDF]

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 EndocrinologyHome page
M. R. Druce, C. J. Small, and S. R. Bloom
Minireview: Gut Peptides Regulating Satiety
Endocrinology, June 1, 2004; 145(6): 2660 - 2665.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
A. Sahu
Minireview: A Hypothalamic Role in Energy Balance with Special Emphasis on Leptin
Endocrinology, June 1, 2004; 145(6): 2613 - 2620.
[Abstract] [Full Text] [PDF]

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 Hum Mol GenetHome page
A. Schmidt, B. Marescau, E. A. Boehm, W. K. J. Renema, R. Peco, A. Das, R. Steinfeld, S. Chan, J. Wallis, M. Davidoff, et al.
Severely altered guanidino compound levels, disturbed body weight homeostasis and impaired fertility in a mouse model of guanidinoacetate N-methyltransferase (GAMT) deficiency
Hum. Mol. Genet., May 1, 2004; 13(9): 905 - 921.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
J. G. Hohmann, D. N. Teklemichael, D. Weinshenker, D. Wynick, D. K. Clifton, and R. A. Steiner
Obesity and Endocrine Dysfunction in Mice with Deletions of both Neuropeptide Y and Galanin
Mol. Cell. Biol., April 1, 2004; 24(7): 2978 - 2985.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
A. P. Goldstone, E. L. Thomas, A. E. Brynes, G. Castroman, R. Edwards, M. A. Ghatei, G. Frost, A. J. Holland, A. B. Grossman, M. Korbonits, et al.
Elevated Fasting Plasma Ghrelin in Prader-Willi Syndrome Adults Is Not Solely Explained by Their Reduced Visceral Adiposity and Insulin Resistance
J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1718 - 1726.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
E. Karteris, J. Chen, and H. S. Randeva
Expression of Human Prepro-Orexin and Signaling Characteristics of Orexin Receptors in the Male Reproductive System
J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1957 - 1962.
[Abstract] [Full Text] [PDF]

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 Reproductive SciencesHome page
M. A. El-Haddad, M. Desai, D. Gayle, and M. G. Ross
In Utero Development of Fetal Thirst and Appetite: Potential for Programming
Reproductive Sciences, April 1, 2004; 11(3): 123 - 130.
[Abstract] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
K. Kiwaki, C. M. Kotz, C. Wang, L. Lanningham-Foster, and J. A. Levine
Orexin A (hypocretin 1) injected into hypothalamic paraventricular nucleus and spontaneous physical activity in rats
Am J Physiol Endocrinol Metab, April 1, 2004; 286(4): E551 - E559.
[Abstract] [Full Text] [PDF]

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 FASEB J.Home page
A. INUI, A. ASAKAWA, C. Y. BOWERS, G. MANTOVANI, A. LAVIANO, M. M. MEGUID, and M. FUJIMIYA
Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocrine organ
FASEB J, March 1, 2004; 18(3): 439 - 456.
[Abstract] [Full Text] [PDF]

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 J. Nutr.Home page
S. Fahrenkrog, T. Harder, E. Stolaczyk, K. Melchior, K. Franke, J. W. Dudenhausen, and A. Plagemann
Cross-Fostering to Diabetic Rat Dams Affects Early Development of Mediobasal Hypothalamic Nuclei Regulating Food Intake, Body Weight, and Metabolism
J. Nutr., March 1, 2004; 134(3): 648 - 654.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
R. Burcelin, M. Uldry, M. Foretz, C. Perrin, A. Dacosta, M. Nenniger-Tosato, J. Seydoux, S. Cotecchia, and B. Thorens
Impaired Glucose Homeostasis in Mice Lacking the {alpha}1b-Adrenergic Receptor Subtype
J. Biol. Chem., January 9, 2004; 279(2): 1108 - 1115.
[Abstract] [Full Text] [PDF]

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 J. Exp. Biol.Home page
W. L. Peacock, E. Krol, K. M. Moar, J. S. McLaren, J. G. Mercer, and J. R. Speakman
Photoperiodic effects on body mass, energy balance and hypothalamic gene expression in the bank vole
J. Exp. Biol., January 1, 2004; 207(1): 165 - 177.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
P. D. Raposinho, T. Pedrazzini, R. B. White, R. D. Palmiter, and M. L. Aubert
Chronic Neuropeptide Y Infusion into the Lateral Ventricle Induces Sustained Feeding and Obesity in Mice Lacking Either Npy1r or Npy5r Expression
Endocrinology, January 1, 2004; 145(1): 304 - 310.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
A. Randich, P. C. Chandler, H. C. Mebane, M. E. Turnbach, S. T. Meller, G. R. Kelm, and J. E. Cox
Jejunal administration of linoleic acid increases activity of neurons in the paraventricular nucleus of the hypothalamus
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2004; 286(1): R166 - R173.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
U. Nordheim and K. G. Hofbauer
Stimulation of NPY Y2 receptors by PYY3-36 reveals divergent cardiovascular effects of endogenous NPY in rats on different dietary regimens
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2004; 286(1): R138 - R142.
[Abstract] [Full Text]

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 Physiol. GenomicsHome page
J. Arens, K. M. Moar, S. Eiden, K. Weide, I. Schmidt, J. G. Mercer, E. Simon, and H.-W. Korf
Age-dependent hypothalamic expression of neuropeptides in wild-type and melanocortin-4 receptor-deficient mice
Physiol Genomics, December 16, 2003; 16(1): 38 - 46.
[Abstract] [Full Text] [PDF]


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