ReviewThoughts for Food : Brain Mechanisms and Peripheral Energy Balance

The past decade has witnessed dramatic advancements regarding the neuroendocrine control of food intake and energy homeostasis and the effects of peripheral metabolic signals on the brain. The development of molecular and genetic tools to visualize and selectively manipulate components of homeostatic systems, in combination with well-established neuroanatomical, electrophysiological, behavioral, and pharmacological techniques, are beginning to provide a clearer picture of the intricate circuits and mechanisms of these complex processes. In this review, we attempt to provide some highlights of these advancements and pinpoint some of the shortcomings of the current understanding of the brain's involvement in the regulation of daily energy homeostasis.

[1]  A. Pol.  Weighing the Role of Hypothalamic Feeding Neurotransmitters , 2003, Neuron.

[2]  Kimberly R. Clark,et al.  Physiological Properties of Hypothalamic MCH Neurons Identified with Selective Expression of Reporter Gene after Recombinant Virus Infection , 2004, Neuron.

[3]  J. Flier,et al.  Melanin-concentrating hormone: a functional melanocortin antagonist in the hypothalamus. , 1998, The American journal of physiology.

[4]  E. H. Goulding,et al.  Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor , 2003, Nature Neuroscience.

[5]  R. Palmiter,et al.  Attenuation of the Obesity Syndrome of ob/ob Mice by the Loss of Neuropeptide Y , 1996, Science.

[6]  Liping Zhao,et al.  Loss of steroidogenic factor 1 alters cellular topography in the mouse ventromedial nucleus of the hypothalamus. , 2004, Journal of neurobiology.

[7]  S. Kalra,et al.  Food deprivation and ingestion induce reciprocal changes in neuropeptide Y concentrations in the paraventricular nucleus , 1988, Peptides.

[8]  P. Shizgal,et al.  Modulation of brain reward circuitry by leptin. , 2000, Science.

[9]  R. Jaenisch,et al.  Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity. , 2001, Molecular endocrinology.

[10]  T. Sakurai,et al.  Ghrelin-induced food intake is mediated via the orexin pathway. , 2003, Endocrinology.

[11]  Fred W. Turek,et al.  Obesity and Metabolic Syndrome in Circadian Clock Mutant Mice , 2005, Science.

[12]  C. Léránth,et al.  Heterogeneity in the neuropeptide Y-containing neurons of the rat arcuate nucleus: GABAergic and non-GABAergic subpopulations , 1997, Brain Research.

[13]  S. Shioda,et al.  Immunohistochemical localization of leptin receptor in the rat brain , 1998, Neuroscience Letters.

[14]  B. M. King,et al.  The rise, fall, and resurrection of the ventromedial hypothalamus in the regulation of feeding behavior and body weight , 2006, Physiology & Behavior.

[15]  R. Cone.  Anatomy and regulation of the central melanocortin system , 2005, Nature Neuroscience.

[16]  Clifford B. Saper,et al.  Unraveling the central nervous system pathways underlying responses to leptin , 1998, Nature Neuroscience.

[17]  S. Carr,et al.  Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. , 1998, Cell.

[18]  Y Itakura,et al.  Brain‐derived neurotrophic factor ameliorates lipid metabolism in diabetic mice , 2002, Diabetes, obesity & metabolism.

[19]  R. Cone,et al.  Integration of NPY, AGRP, and Melanocortin Signals in the Hypothalamic Paraventricular Nucleus Evidence of a Cellular Basis for the Adipostat , 1999, Neuron.

[20]  Evidence for seasonal plasticity in the gonadotropin-releasing hormone (GnRH) system of the ewe: changes in synaptic inputs onto GnRH neurons. , 1997, Endocrinology.

[21]  Michael W. Schwartz,et al.  Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons , 1998, Nature Neuroscience.

[22]  A. Sahu.  Interactions of neuropeptide Y, hypocretin-I (orexin A) and melanin-concentrating hormone on feeding in rats , 2002, Brain Research.

[23]  T. Horvath,et al.  Oestrogen-induced changes in the synaptology of the monkey (Cercopithecus aethiops) arcuate nucleus during gonadotropin feedback. , 2001, Journal of neuroendocrinology.

[24]  G. Sanacora,et al.  Increased hypothalamic content of preproneuropeptide Y messenger ribonucleic acid in genetically obese Zucker rats and its regulation by food deprivation. , 1990, Endocrinology.

[25]  Dickson,et al.  Growth Hormone Secretagogue Activation of the Arcuate Nucleus and Brainstem Occurs Via a Non‐Noradrenergic Pathway , 2000, Journal of neuroendocrinology.

[26]  R. Palmiter,et al.  Dopamine Production in the Caudate Putamen Restores Feeding in Dopamine-Deficient Mice , 2001, Neuron.

[27]  M. Ghatei,et al.  Increased neuropeptide-Y messenger ribonucleic acid (mRNA) and decreased neurotensin mRNA in the hypothalamus of the obese (ob/ob) mouse. , 1993, Endocrinology.

[28]  M. Low,et al.  Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus , 2001, Nature.

[29]  R. Cone,et al.  Independent and additive effects of central POMC and leptin pathways on murine obesity. , 1997, Science.

[30]  J. Parisi,et al.  Localization of leptin receptor in the human brain. , 1997, Neuroendocrinology.

[31]  M. Traebert,et al.  Site-specific effects of ghrelin on the neuronal activity in the hypothalamic arcuate nucleus , 2003, Neuroscience Letters.

[32]  P. Luiten,et al.  The projections of the dorsomedial hypothalamic nucleus in the rat , 1986, Brain Research Bulletin.

[33]  Mitsuru Nishiyama,et al.  GABA Release from Proopiomelanocortin Neurons , 2004, The Journal of Neuroscience.

[34]  T. Horvath.  Neuropeptide-Y innervation of beta-endorphin-containing cells in the rat mediobasal hypothalamus: a light and electron microscopic double immunostaining analysis [published erratum appears in Endocrinology 1996 Feb;137(2):532] , 1992 .

[35]  C. Saper,et al.  Chemical characterization of leptin‐activated neurons in the rat brain , 2000, The Journal of comparative neurology.

[36]  Robert A. McGovern,et al.  Divergence of Melanocortin Pathways in the Control of Food Intake and Energy Expenditure , 2005, Cell.

[37]  L. P. Morin.  The circadian visual system , 1994, Brain Research Reviews.

[38]  T. Hökfelt,et al.  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 , 1998, The Journal of comparative neurology.

[39]  C. Saper,et al.  From Lesions to Leptin Hypothalamic Control of Food Intake and Body Weight , 1999, Neuron.

[40]  B. Lowell,et al.  Mice lacking melanin-concentrating hormone are hypophagic and lean , 1998, Nature.

[41]  G. Colditz,et al.  The epidemic of obesity. , 2004, The Journal of clinical endocrinology and metabolism.

[42]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1994, Nature.

[43]  T. Hökfelt,et al.  The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[44]  S. Dickson,et al.  PRECLINICAL STUDY: Ghrelin stimulates locomotor activity and accumbal dopamine‐overflow via central cholinergic systems in mice: implications for its involvement in brain reward , 2006, Addiction biology.

[45]  W. Sadee,et al.  A synthetic human Agouti‐related protein‐(83–132)‐NH2 fragment is a potent inhibitor of melanocortin receptor function , 1998, FEBS letters.

[46]  S. Whitebread,et al.  Ghrelin Acts on Leptin‐Responsive Neurones in the Rat Arcuate Nucleus , 2002, Journal of neuroendocrinology.

[47]  R. Palmiter,et al.  Reward without Dopamine , 2003, The Journal of Neuroscience.

[48]  R. Wise.  Brain Reward Circuitry Insights from Unsensed Incentives , 2002, Neuron.

[49]  F. Leslie,et al.  Expression of the melanin‐concentrating hormone (MCH) receptor mRNA in the rat brain , 2001, The Journal of comparative neurology.

[50]  S. Carr,et al.  Orexins and Orexin Receptors: A Family of Hypothalamic Neuropeptides and G Protein-Coupled Receptors that Regulate Feeding Behavior , 1998, Cell.

[51]  C. Saper,et al.  Expression of melanocortin 4 receptor mRNA in the central nervous system of the rat , 2003, The Journal of comparative neurology.

[52]  L. Záborszky,et al.  Intrahypothalamic connections: An electron microscopic study in the rat , 1979, Experimental Brain Research.

[53]  Gordon M G Shepherd,et al.  Topographic mapping of VMH → arcuate nucleus microcircuits and their reorganization by fasting , 2005, Nature Neuroscience.

[54]  Robert A. McGovern,et al.  Leptin Directly Activates SF1 Neurons in the VMH, and This Action by Leptin Is Required for Normal Body-Weight Homeostasis , 2006, Neuron.

[55]  Jon T. Willie,et al.  Genetic Ablation of Orexin Neurons in Mice Results in Narcolepsy, Hypophagia, and Obesity , 2001, Neuron.

[56]  W. Cowan,et al.  The efferent connections of the ventromedial nucleus of the hypothalamus of the rat , , 1976, The Journal of comparative neurology.

[57]  J. Brobeck,et al.  Experimental Hypothalamic Hyperphagia in the Albino Rat * , 1943, The Yale journal of biology and medicine.

[58]  M. G. Dube,et al.  Food intake elicited by central administration of orexins/hypocretins: identification of hypothalamic sites of action 1 This study was presented in part at the 28th Annual Meeting of the Society for Neuroscience, Los Angeles, CA, in November 1998. 1 , 1999, Brain Research.

[59]  R. Buijs,et al.  Ventromedial arcuate nucleus communicates peripheral metabolic information to the suprachiasmatic nucleus. , 2006, Endocrinology.

[60]  D. Coleman.  Diabetes-Obesity Syndromes in Mice , 1982, Diabetes.

[61]  G. Barsh,et al.  Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. , 1997, Science.

[62]  Xiao-Bing Gao,et al.  Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. , 2006, The Journal of clinical investigation.

[63]  E. Maywood,et al.  Expression of mCLOCK and Other Circadian Clock‐Relevant Proteins in the Mouse Suprachiasmatic Nuclei , 2003, Journal of neuroendocrinology.

[64]  J. Brobeck,et al.  Localization of a “Feeding Center” in the Hypothalamus of the Rat , 1951, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[65]  C. Léránth,et al.  Neuropeptide-Y innervation of beta-endorphin-containing cells in the rat mediobasal hypothalamus: a light and electron microscopic double immunostaining analysis. , 1992, Endocrinology.

[66]  H. Grill,et al.  The Neuroanatomical Axis for Control of Energy Balance , 2002, Frontiers in Neuroendocrinology.

[67]  S. Dickson,et al.  Printed in U.S.A. Copyright © 1997 by The Endocrine Society Induction of c-fos Messenger Ribonucleic Acid in Neuropeptide Y and Growth Hormone (GH)-Releasing Factor Neurons in the Rat Arcuate Nucleus Following Systemic Injection of the GH Secretagogue, GH , 2022 .

[68]  B. L. Rollins,et al.  Effects of amygdala lesions on body weight, conditioned taste aversion, and neophobia , 2001, Physiology & Behavior.

[69]  Roy G. Smith,et al.  Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. , 1997, Brain research. Molecular brain research.

[70]  T. Hyde,et al.  Autoradiographic localization of leptin binding in the choroid plexus of ob/ob and db/db mice. , 1996, Biochemical and biophysical research communications.

[71]  Victor J. Hruby,et al.  Role of melanocortinergic neurons in feeding and the agouti obesity syndrome , 1997, Nature.

[72]  R. Palmiter,et al.  Dopamine is required for hyperphagia in Lepob/ob mice , 2000, Nature Genetics.

[73]  T. Horvath,et al.  The floating blueprint of hypothalamic feeding circuits , 2004, Nature Reviews Neuroscience.

[74]  A. Tsuchida,et al.  Antiobesity and antidiabetic effects of brain-derived neurotrophic factor in rodent models of leptin resistance , 2003, International Journal of Obesity.

[75]  N. Hanley,et al.  Steroidogenic factor 1: an essential mediator of endocrine development. , 2002, Recent progress in hormone research.

[76]  M. Tschöp,et al.  A role for β-melanocyte-stimulating hormone in human body-weight regulation , 2006 .

[77]  T. Horvath,et al.  0013-7227/01/$03.00/0 Endocrinology 142(10):4163–4169 Printed in U.S.A. Copyright © 2001 by The Endocrine Society Minireview: Ghrelin and the Regulation of Energy , 2022 .

[78]  K. Berridge.  Food reward: Brain substrates of wanting and liking , 1996, Neuroscience & Biobehavioral Reviews.

[79]  C. Saper,et al.  Expression of ghrelin receptor mRNA in the rat and the mouse brain , 2006, The Journal of comparative neurology.

[80]  T. O'donohue,et al.  Coexistence of neuropeptide Y and somatostatin in rat and human cortical and rat hypothalamic neurons , 1984, Neuroscience Letters.

[81]  Jun Lu,et al.  Afferents to the Ventrolateral Preoptic Nucleus , 2002, The Journal of Neuroscience.

[82]  J. McGarry,et al.  Knockout mice lacking steroidogenic factor 1 are a novel genetic model of hypothalamic obesity. , 2002, Endocrinology.

[83]  J. Brobeck.  Mechanism of the development of obesity in animals with hypothalamic lesions. , 1946, Physiological reviews.

[84]  F E Bloom,et al.  The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[85]  L. Rossetti,et al.  Minireview: nutrient sensing and the regulation of insulin action and energy balance. , 2003, Endocrinology.

[86]  T. Horvath,et al.  Input organization and plasticity of hypocretin neurons: possible clues to obesity's association with insomnia. , 2005, Cell metabolism.

[87]  J. Morley,et al.  Neuropeptide Y increases food intake in mice. , 1987, The American journal of physiology.

[88]  M. Schwartz,et al.  Leptin Sensitive Neurons in the Hypothalamus , 1999, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[89]  D. Wilkin,et al.  Neuron , 2001, Brain Research.

[90]  Joshua J Gooley,et al.  The dorsomedial hypothalamic nucleus is critical for the expression of food-entrainable circadian rhythms , 2006, Nature Neuroscience.

[91]  R. Palmiter,et al.  Dysregulation of dopamine signaling in the dorsal striatum inhibits feeding , 2005, Brain Research.

[92]  B. Lowell,et al.  Leptin Receptor Signaling in POMC Neurons Is Required for Normal Body Weight Homeostasis , 2004, Neuron.

[93]  H. Davidowa,et al.  Food deprivation decreases responsiveness of ventromedial hypothalamic neurons to melanocortins , 2004, Journal of neuroscience research.

[94]  D. Vicent,et al.  Functional interactions between melanin-concentrating hormone, neuropeptide Y, and anorectic neuropeptides in the rat hypothalamus. , 1998, Diabetes.

[95]  A. N. van den Pol,et al.  Neurons Containing Hypocretin (Orexin) Project to Multiple Neuronal Systems , 1998, The Journal of Neuroscience.

[96]  S. Woods,et al.  CNS Melanocortin System Involvement in the Regulation of Food Intake , 2000, Hormones and Behavior.

[97]  R. Cone,et al.  The central melanocortin system and the integration of short- and long-term regulators of energy homeostasis. , 2004, Recent progress in hormone research.

[98]  M. Myers,et al.  The role of leptin receptor signaling in feeding and neuroendocrine function , 2003, Trends in Endocrinology & Metabolism.

[99]  D. Macneil,et al.  Neither Agouti-Related Protein nor Neuropeptide Y Is Critically Required for the Regulation of Energy Homeostasis in Mice , 2002, Molecular and Cellular Biology.

[100]  S. Lin,et al.  Localization of leptin receptor mRNA expression in mouse brain. , 1996, Neuroreport.

[101]  HJ Grill,et al.  Interoceptive and integrative contributions of forebrain and brainstem to energy balance control , 2001, International Journal of Obesity.

[102]  P. Wellman,et al.  Augmentation of cocaine hyperactivity in rats by systemic ghrelin , 2005, Regulatory Peptides.

[103]  N. Hoggard,et al.  Localization of leptin receptor mRNA and the long form splice variant (Ob‐Rb) in mouse hypothalamus and adjacent brain regions by in situ hybridization , 1996, FEBS letters.

[104]  P. Widdowson,et al.  Altered energy balance causes selective changes in melanocortin-4(MC4-R), but not melanocortin-3 (MC3-R), receptors in specific hypothalamic regions: further evidence that activation of MC4-R is a physiological inhibitor of feeding. , 1999, Diabetes.

[105]  L. P. Morin,et al.  The circadian visual system, 2005 , 2006, Brain Research Reviews.

[106]  S. Olshansky,et al.  A potential decline in life expectancy in the United States in the 21st century. , 2005, The New England journal of medicine.

[107]  G. Barsh,et al.  Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area , 1998, The Journal of comparative neurology.

[108]  L. Bellinger,et al.  The dorsomedial hypothalamic nucleus and its role in ingestive behavior and body weight regulation: Lessons learned from lesioning studies , 2002, Physiology & Behavior.

[109]  Jon T. Willie,et al.  Distinct Narcolepsy Syndromes in Orexin Receptor-2 and Orexin Null Mice Molecular Genetic Dissection of Non-REM and REM Sleep Regulatory Processes , 2003, Neuron.

[110]  E. Sugaru,et al.  Brain‐derived neurotrophic factor (BDNF) regulates glucose and energy metabolism in diabetic mice , 2002, Diabetes/metabolism research and reviews.

[111]  P. G. Clifton,et al.  Little and often: ingestive behavior patterns following hippocampal lesions in rats. , 1998, Behavioral neuroscience.

[112]  S. W. Ranson,et al.  The relation of various hypothalamic lesions to adiposity in the rat , 1942 .

[113]  Thomas M. Harris,et al.  Use of Laser-Capture Microdissection for the Identification of Marker Genes for the Ventromedial Hypothalamic Nucleus , 2005, The Journal of Neuroscience.

[114]  Á. Párducz,et al.  Hormonal enhancement of neuronal firing is linked to structural remodelling of excitatory and inhibitory synapses , 2002, The European journal of neuroscience.

[115]  Stanley J. Watson,et al.  Differential Distribution and Regulation of OX1 and OX2 Orexin/Hypocretin Receptor Messenger RNA in the Brain upon Fasting , 2000, Hormones and Behavior.

[116]  S. Honma,et al.  Clock gene expressions in the suprachiasmatic nucleus and other areas of the brain during rhythm splitting in CS mice. , 2001, Brain research. Molecular brain research.

[117]  S. Bloom,et al.  Melanin-concentrating hormone (MCH) suppresses thyroid stimulating hormone (TSH) release, in vivo and in vitro, via the hypothalamus and the pituitary. , 2001, Endocrinology.

[118]  S. Bloom,et al.  The effect of the orexins on food intake: comparison with neuropeptide Y, melanin-concentrating hormone and galanin. , 1999, The Journal of endocrinology.

[119]  S. Dickson,et al.  Systemic Administration of Ghrelin Induces Fos and Egr‐1 Proteins in the Hypothalamic Arcuate Nucleus of Fasted and Fed Rats , 2000, Journal of neuroendocrinology.

[120]  R. Palmiter,et al.  Viral Gene Delivery Selectively Restores Feeding and Prevents Lethality of Dopamine-Deficient Mice , 1999, Neuron.

[121]  Jon T. Willie,et al.  Narcolepsy in orexin Knockout Mice Molecular Genetics of Sleep Regulation , 1999, Cell.

[122]  A. Fournier,et al.  Effects of NPY and NPY2–36 on body temperature and food intake following administration into hypothalamic nuclei , 1995, Brain Research Bulletin.

[123]  S. W. Ranson,et al.  Hypothalamic lesions and adiposity in the rat , 1940 .

[124]  A. G. Roseberry,et al.  Rapid Rewiring of Arcuate Nucleus Feeding Circuits by Leptin , 2004, Science.

[125]  C. Saper,et al.  Colocalization of orexin a and glutamate immunoreactivity in axon terminals in the tuberomammillary nucleus in rats , 2003, Neuroscience.

[126]  S. Gammeltoft,et al.  A role for melanin-concentrating hormone in the central regulation of feeding behaviour , 1996, Nature.

[127]  R. Cone,et al.  Differential effects of melanocortin peptides on neural melanocortin receptors. , 1994, Molecular pharmacology.

[128]  T. Zucker,et al.  Fat accretion and growth in the rat. , 1996, Obesity research.

[129]  G. Cooney,et al.  Adrenalectomy reduces neuropeptide Y-induced insulin release and NPY receptor expression in the rat ventromedial hypothalamus. , 2000, The Journal of clinical investigation.

[130]  E. Stellar,et al.  The physiology of motivation. , 1954, Psychological review.

[131]  E. Maywood,et al.  Expression of clock gene products in the suprachiasmatic nucleus in relation to circadian behaviour. , 2003, Novartis Foundation symposium.

[132]  S. O’Rahilly,et al.  A POMC variant implicates beta-melanocyte-stimulating hormone in the control of human energy balance. , 2006, Cell metabolism.

[133]  Alain Dagher,et al.  Feeding-induced dopamine release in dorsal striatum correlates with meal pleasantness ratings in healthy human volunteers , 2003, NeuroImage.

[134]  W. Armstrong,et al.  Reorganization of the Dendritic Trees of Oxytocin and Vasopressin Neurons of the Rat Supraoptic Nucleus during Lactation , 1998, The Journal of Neuroscience.

[135]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1995, Nature.

[136]  P S Kalra,et al.  Neuropeptide Y and human pancreatic polypeptide stimulate feeding behavior in rats. , 1984, Endocrinology.

[137]  M. G. Dube,et al.  Evidence for the existence of distinct central appetite, energy expenditure, and ghrelin stimulation pathways as revealed by hypothalamic site-specific leptin gene therapy. , 2002, Endocrinology.

[138]  Z. Bendová,et al.  Seasonal molecular timekeeping within the rat circadian clock. , 2004, Physiological research.

[139]  D. Figlewicz,et al.  Adiposity signals and food reward: expanding the CNS roles of insulin and leptin. , 2003, American journal of physiology. Regulatory, integrative and comparative physiology.

[140]  A. Kalsbeek,et al.  The biological clock tunes the organs of the body: timing by hormones and the autonomic nervous system. , 2003, The Journal of endocrinology.

[141]  M. Bear,et al.  LTP and LTD An Embarrassment of Riches , 2004, Neuron.

[142]  M. Low,et al.  The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis , 2001, International Journal of Obesity.

[143]  H. Berthoud,et al.  Multiple neural systems controlling food intake and body weight , 2002, Neuroscience & Biobehavioral Reviews.

[144]  P S Kalra,et al.  Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. , 1999, Endocrine reviews.

[145]  R. Palmiter,et al.  NPY/AgRP Neurons Are Essential for Feeding in Adult Mice but Can Be Ablated in Neonates , 2005, Science.

[146]  S. Kalra,et al.  Evidence that NPY-containing neurons in the brainstem project into selected hypothalamic nuclei: implication in feeding behavior , 1988, Brain Research.

[147]  M. Mortrud,et al.  Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. , 1994, Molecular endocrinology.

[148]  Á. Párducz,et al.  Neuroplastic changes in the hypothalamic arcuate nucleus: The estradiol effect is accompanied by increased exoendocytotic activity of neuronal membranes , 1996, Cellular and Molecular Neurobiology.

[149]  S. Oliet,et al.  Neuronal, glial and synaptic remodeling in the adult hypothalamus: functional consequences and role of cell surface and extracellular matrix adhesion molecules , 2004, Neurochemistry International.

[150]  R. Darnell,et al.  Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[151]  J. Friedman,et al.  Late-Onset Leanness in Mice with Targeted Ablation of Melanin Concentrating Hormone Neurons , 2006, The Journal of Neuroscience.

[152]  Thorsten Buch,et al.  Agouti-related peptide–expressing neurons are mandatory for feeding , 2005, Nature Neuroscience.

[153]  L. Swanson,et al.  Organization of projections from the ventromedial nucleus of the hypothalamus: A Phaseolus vulgaris‐Leucoagglutinin study in the rat , 1994, The Journal of comparative neurology.

[154]  R. Seeley,et al.  The critical role of the melanocortin system in the control of energy balance. , 2004, Annual review of nutrition.

[155]  R. Wise,et al.  How can drug addiction help us understand obesity? , 2005, Nature Neuroscience.

[156]  William A. Alaynick,et al.  A role for dopamine in feeding responses produced by orexigenic agents , 2004, Brain Research.

[157]  T. Horvath,et al.  Fasting activates the nonhuman primate hypocretin (orexin) system and its postsynaptic targets. , 2003, Endocrinology.

[158]  A. N. van den Pol,et al.  Synaptic Interaction between Hypocretin (Orexin) and Neuropeptide Y Cells in the Rodent and Primate Hypothalamus: A Novel Circuit Implicated in Metabolic and Endocrine Regulations , 1999, The Journal of Neuroscience.

[159]  R. D. Myers,et al.  Antisense to NPY-Y1 demonstrates that Y1 receptors in the hypothalamus underlie NPY hypothermia and feeding in rats , 1996, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[160]  A. Yamanaka,et al.  Orexin-induced food intake involves neuropeptide Y pathway , 2000, Brain Research.

[161]  Á. Párducz,et al.  Gonadal hormones as promoters of structural synaptic plasticity: Cellular mechanisms , 1994, Progress in Neurobiology.

[162]  J. Halaas,et al.  Leptin and the regulation of body weight in mammals , 1998, Nature.

[163]  R. Palmiter,et al.  Feeding behavior in dopamine-deficient mice. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[164]  S. Bloom,et al.  A C-terminal fragment of Agouti-related protein increases feeding and antagonizes the effect of alpha-melanocyte stimulating hormone in vivo. , 1998, Endocrinology.

[165]  S. H. Moss,et al.  The melanocortin (MC3) receptor from rat hypothalamus: Photoaffinity labelling and binding of alanine‐substituted α‐MSH analogues , 1994, FEBS letters.

[166]  A. Pol,et al.  Melanin concentrating hormone depresses synaptic activity of glutamate and GABA neurons from rat lateral hypothalamus , 2001, The Journal of physiology.

[167]  R. Skoda,et al.  Leptin Receptor Immunoreactivity in Chemically Defined Target Neurons of the Hypothalamus , 1998, The Journal of Neuroscience.

[168]  S. Bouret,et al.  Comparative distribution of mRNA encoding the growth hormone secretagogue‐receptor (GHS‐R) in Microcebus murinus (Primate, Lemurian) and rat forebrain and pituitary , 2001 .

[169]  Jun Lu,et al.  Critical Role of Dorsomedial Hypothalamic Nucleus in a Wide Range of Behavioral Circadian Rhythms , 2003, The Journal of Neuroscience.

[170]  N. Tritos,et al.  Characterization of melanin concentrating hormone and preproorexin expression in the murine hypothalamus , 2001, Brain Research.

[171]  S. Miyata,et al.  Structural dynamics of neural plasticity in the supraoptic nucleus of the rat hypothalamus during dehydration and rehydration , 1994, Brain Research Bulletin.

[172]  S. Woods,et al.  Central nervous system control of food intake , 2000, Nature.