Integrative neurobiology of energy homeostasis-neurocircuits, signals and mediators

Frontiers in Neuroendocrinology

Volumn 31, Issue 1, 2010, Pages 4-15

  Sánchez Lasheras, Carmen ^a,b,c,d   Christine Konner A ^a,b,c,d   Brüning, Jens C ^a,b,c,d  

^a UNIVERSITY OF COLOGNE   (Germany)

^b UNIVERSITY OF COLOGNE   (Germany)

^c UNIVERSITY HOSPITAL OF COLOGNE   (Germany)

^d MAX PLANCK INSTITUTE FOR BIOLOGY OF AGEING   (Germany)

Author keywords

Arcuate nucleus; Brain; Energy homeostasis; Insulin; Leptin; Nutrient sensing; Reward system

Indexed keywords

FATTY ACID; GLUCOSE; INSULIN; LEPTIN; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE;

ADIPOCYTE; ADIPOSE TISSUE; BODY WEIGHT; BRAIN FUNCTION; CELL FUNCTION; CENTRAL NERVOUS SYSTEM; DOPAMINERGIC SYSTEM; ENERGY BALANCE; ENERGY METABOLISM; FEEDING BEHAVIOR; FOOD INTAKE; GLUCONEOGENESIS; GLUCOSE HOMEOSTASIS; GLUCOSE METABOLISM; HORMONE ACTION; HUMAN; HYPOTHALAMUS; LATERAL HYPOTHALAMUS; LIVER; MITOCHONDRIAL RESPIRATION; NERVE CELL PLASTICITY; NEUROBIOLOGY; NEUROMODULATION; NONHUMAN; PANCREAS; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; WEIGHT GAIN; WEIGHT REDUCTION; ZONA INCERTA;

ANIMALS; BODY WEIGHT; BRAIN; DIABETES MELLITUS; EATING; ENERGY METABOLISM; GLUCOSE; HOMEOSTASIS; HUMANS; HYPOTHALAMUS; INSULIN; LEPTIN; NEUROSECRETORY SYSTEMS; NUTRITIONAL PHYSIOLOGICAL PHENOMENA; OBESITY; SIGNAL TRANSDUCTION;

EID: 72449184473     PISSN: 00913022     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.yfrne.2009.08.002     Document Type: Review

References (211)

1. Abizaid A., Liu Z.W., Andrews Z.B., Shanabrough M., Borok E., Elsworth J.D., Roth R.H., Sleeman M.W., Picciotto M.R., Tschop M.H., Gao X.B., and Horvath T.L. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. J. Clin. Invest. 116 (2006) 3229-3239
2. Agmo A., Galvan A., and Talamantes B. Reward and reinforcement produced by drinking sucrose: two processes that may depend on different neurotransmitters. Pharmacol. Biochem. Behav. 52 (1995) 403-414
3. Alessi D.R., Deak M., Casamayor A., Caudwell F.B., Morrice N., Norman D.G., Gaffney P., Reese C.B., MacDougall C.N., Harbison D., Ashworth A., and Bownes M. 3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase. Curr. Biol. 7 (1997) 776-789
4. Almli C.R., and Golden G.T. Serial lateral hypothalamic destruction: infancy and adulthood. Exp. Neurol. 53 (1976) 646-662
5. Anand B.K., and Brobeck J.R. Localization of a" feeding center" in the hypothalamus of the rat. Proc. Soc. Exp. Biol. Med. 77 (1951) 323-324
6. Andrews Z.B., Liu Z.W., Walllingford N., Erion D.M., Borok E., Friedman J.M., Tschöp M.H., Shanabrough M., Cline G., Shulman G.I., Coppola A., Gao X.B., Horvath T.L., and Diano S. UCP2 mediates ghrelin's action on NPY/AgRP neurons by lowering free radicals. Nature 454 (2008) 846-851
7. Auerbach J.M., and Segal M. Peroxide modulation of slow onset potentiation in rat hippocampus. J. Neurosci. 17 (1997) 8695-8701
8. Avshalumov M.V., Bao L., Patel J.C., and Rice M.E. H2O2 signaling in the nigrostriatal dopamine pathway via ATP-sensitive potassium channels: issues and answers. Antioxid. Redox Signal 9 (2007) 219-231
9. Backer J.M., Myers M.G., Shoelson S.E., Chin D.J., Sun X.J., Miralpeix M., Hu P., Margolis B., Skolnik E.Y., and Schlessinger J. Phosphatidylinositol 3′-kinase is activated by association with IRS-1 during insulin stimulation. EMBO J. 11 (1992) 3469-3479
10. Bagnasco M., Dube M.G., Kalra P.S., and Kalra S.P. Evidence for the existence of distinct central appetite, energy expenditure, and ghrelin stimulation pathways as revealed by hypothalamic site-specific leptin gene therapy. Endocrinology 143 (2002) 4409-4421
11. Balthasar N., Coppari R., McMinn J., Liu S.M., Lee C.E., Tang V., Kenny C.D., McGovern R.A., Chua S.C., Elmquist J.K., and Lowell B.B. Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron 42 (2004) 983-991
12. Banks A.S., Davis S.M., Bates S.H., and Myers M.G. Activation of downstream signals by the long form of the leptin receptor. J. Biol. Chem. 275 (2000) 14563-14572
13. Bates S.H., Stearns W.H., Dundon T.A., Schubert M., Tso A.W., Wang Y., Banks A.S., Lavery H.J., Haq A.K., Maratos-Flier E., Neel B.G., Schwartz M.W., and Myers M.G. STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature 421 (2003) 856-859
14. Baukrowitz T., Schulte U., Oliver D., Herlitze S., Krauter T., Tucker S.J., Ruppersberg J.P., and Fakler B. PIP2 and PIP as determinants for ATP inhibition of KATP channels. Science 282 (1998) 1141-1144
15. Baumann H., Morella K.K., White D.W., Dembski M., Bailon P.S., Kim H., Lai C.F., and Tartaglia L.A. The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors. Proc. Natl. Acad. Sci. USA 93 (1996) 8374-8378
16. Belgardt B.F., Husch A., Rother E., Ernst M.B., Wunderlich F.T., Hampel B., Klöckener T., Alessi D., Kloppenburg P., and Brüning J.C. PDK1 deficiency in POMC-expressing cells reveals FOXO1-dependent and -independent pathways in control of energy homeostasis and stress response. Cell. Metab. 7 (2008) 291-301
17. Benani A., Troy S., Carmona M.C., Fioramonti X., Lorsignol A., Leloup C., Casteilla L., and Pénicaud L. Role for mitochondrial reactive oxygen species in brain lipid sensing: redox regulation of food intake. Diabetes 56 (2007) 152-160
18. Benoit S.C., Air E.L., Coolen L.M., Strauss R., Jackman A., Clegg D.J., Seeley R.J., and Woods S.C. The catabolic action of insulin in the brain is mediated by melanocortins. J. Neurosci. 22 (2002) 9048-9052
19. Bernardis L.L., and Bellinger L.L. The lateral hypothalamic area revisited: ingestive behavior. Neurosci. Biobehav. Rev. 20 (1996) 189-287
20. Biebermann H., Castañeda T.R., van Landeghem F., von Deimling A., Escher F., Brabant G., Hebebrand J., Hinney A., Tschöp M.H., Grüters A., and Krude H. A role for beta-melanocyte-stimulating hormone in human body-weight regulation. Cell Metab. 3 (2006) 141-146
21. Biggs W.H., Meisenhelder J., Hunter T., Cavenee W.K., and Arden K.C. Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1. Proc. Natl. Acad. Sci. USA 96 (1999) 7421-7426
22. Bina K.G., and Cincotta A.H. Dopaminergic agonists normalize elevated hypothalamic neuropeptide Y and corticotropin-releasing hormone, body weight gain, and hyperglycemia in ob/ob mice. Neuroendocrinology 71 (2000) 68-78
23. Bingham N.C., Anderson K.K., Reuter A.L., Stallings N.R., and Parker K.L. Selective loss of leptin receptors in the ventromedial hypothalamic nucleus results in increased adiposity and a metabolic syndrome. Endocrinology 149 (2008) 2138-2148
24. Bittencourt J.C., Presse F., Arias C., Peto C., Vaughan J., Nahon J.L., Vale W., and Sawchenko P.E. The melanin-concentrating hormone system of the rat brain: an immuno and hybridization histochemical characterization. J. Comp. Neurol. 319 (1992) 218-245
25. Bjørbaek C., Elmquist J.K., Frantz J.D., Shoelson S.E., and Flier J.S. Identification of SOCS-3 as a potential mediator of central leptin resistance. Mol. Cell 1 (1998) 619-625
26. Bjørbaek C., Uotani S., da Silva B., and Flier J.S. Divergent signaling capacities of the long and short isoforms of the leptin receptor. J. Biol. Chem. 272 (1997) 32686-32695
27. Blüher S., Moschos S., Bullen J., Kokkotou E., Maratos-Flier E., Wiegand S.J., Sleeman M.W., Sleemann M.W., and Mantzoros C.S. Ciliary neurotrophic factorAx15 alters energy homeostasis, decreases body weight, and improves metabolic control in diet-induced obese and UCP1-DTA mice. Diabetes 53 (2004) 2787-2796
28. Borgland S.L., Taha S.A., Sarti F., Fields H.L., and Bonci A. Orexin A in the VTA is critical for the induction of synaptic plasticity and behavioral sensitization to cocaine. Neuron 49 (2006) 589-601
29. Bouali S.M., Fournier A., St-Pierre S., and Jolicoeur F.B. Effects of NPY and NPY2-36 on body temperature and food intake following administration into hypothalamic nuclei. Brain Res. Bull. 36 (1995) 131-135
30. Brobeck J.R., Tepperman J., and Long C.N.H. Experimental Hypothalamic Hyperphagia in the Albino Rat. Yale J. Biol. Med. 15 (1943) 831
31. Brunet A., Bonni A., Zigmond M.J., Lin M.Z., Juo P., Hu L.S., Anderson M.J., Arden K.C., Blenis J., and Greenberg M.E. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96 (1999) 857-868
32. Brüning J.C., Gautam D., Burks D.J., Gillette J., Schubert M., Orban P.C., Klein R., Krone W., Müller-Wieland D., and Kahn C.R. Role of brain insulin receptor in control of body weight and reproduction. Science 289 (2000) 2122-2125
33. Buettner C., Muse E.D., Cheng A., Chen L., Scherer T., Pocai A., Su K., Cheng B., Li X., Harvey-White J., Schwartz G.J., Kunos G., and Rossetti L. Leptin controls adipose tissue lipogenesis via central, STAT3-independent mechanisms. Nat. Med. 14 (2008) 667-675
34. Buettner C., Pocai A., Muse E.D., Etgen A.M., Myers M.G., and Rossetti L. Critical role of STAT3 in leptin's metabolic actions. Cell Metab. 4 (2006) 49-60
35. Campbell B.A., and Fibiger H.C. Potentiation of amphetamine-induced arousal by starvation. Nature 233 (1971) 424-425
36. Carroll M.E. Food deprivation produces persistent increases in self-administration behavior during cocaine extinction. NIDA Res. Monogr. 55 (1984) 125-131
37. Chua S.C., Chung W.K., Wu-Peng X.S., Zhang Y., Liu S.M., Tartaglia L., and Leibel R.L. Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor. Science 271 (1996) 994-996
38. Claret M., Smith M.A., Batterham R.L., Selman C., Choudhury A.I., Fryer L.G., Clements M., Al-Qassab H., Heffron H., Xu A.W., Speakman J.R., Barsh G.S., Viollet B., Vaulont S., Ashford M.L., Carling D., and Withers D.J. AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons. J. Clin. Invest. 117 (2007) 2325-2336
39. Cohen P., Zhao C., Cai X., Montez J.M., Rohani S.C., Feinstein P., Mombaerts P., and Friedman J.M. Selective deletion of leptin receptor in neurons leads to obesity. J. Clin. Invest. 108 (2001) 1113-1121
40. Commins S.P., Watson P.M., Padgett M.A., Dudley A., Argyropoulos G., and Gettys T.W. Induction of uncoupling protein expression in brown and white adipose tissue by leptin. Endocrinology 140 (1999) 292-300
41. Considine R.V., Sinha M.K., Heiman M.L., Kriauciunas A., Stephens T.W., Nyce M.R., Ohannesian J.P., Marco C.C., McKee L.J., and Bauer T.L. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. New Engl. J. Med. 334 (1996) 292-295
42. Coppari R., Ichinose M., Lee C.E., Pullen A.E., Kenny C.D., McGovern R.A., Tang V., Liu S.M., Ludwig T., Chua S.C., Lowell B.B., and Elmquist J.K. The hypothalamic arcuate nucleus: a key site for mediating leptin's effects on glucose homeostasis and locomotor activity. Cell Metab. 1 (2005) 63-72
43. Cota D., Proulx K., Smith K.A., Kozma S.C., Thomas G., Woods S.C., and Seeley R.J. Hypothalamic mTOR signaling regulates food intake. Science 312 (2006) 927-930
44. Cowley M.A., Smart J.L., Rubinstein M., Cerdán M.G., Diano S., Horvath T.L., Cone R.D., and Low M.J. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411 (2001) 480-484
45. Delgado J.M., and Anand B.K. Increase of food intake induced by electrical stimulation of the lateral hypothalamus. Am. J. Physiol. 172 (1953) 162-168
46. Deroche V., Marinelli M., Maccari S., Le Moal M., Simon H., and Piazza P.V. Stress-induced sensitization and glucocorticoids. I. Sensitization of dopamine-dependent locomotor effects of amphetamine and morphine depends on stress-induced corticosterone secretion. J. Neurosci. 15 (1995) 7181-7188
47. Dhillon H., Zigman J.M., Ye C., Lee C.E., McGovern R.A., Tang V., Kenny C.D., Christiansen L.M., White R.D., Edelstein E.A., Coppari R., Balthasar N., Cowley M.A., Chua S., Elmquist J.K., and Lowell B.B. Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis. Neuron 49 (2006) 191-203
48. Diano S., Horvath B., Urbanski H.F., Sotonyi P., and Horvath T.L. Fasting activates the nonhuman primate hypocretin (orexin) system and its postsynaptic targets. Endocrinology 144 (2003) 3774-3778
49. Dube M.G., Kalra S.P., and Kalra P.S. Food intake elicited by central administration of orexins/hypocretins: identification of hypothalamic sites of action. Brain Res. 842 (1999) 473-477
50. Elias C.F., Saper C.B., Maratos-Flier E., Tritos N.A., Lee C., Kelly J., Tatro J.B., Hoffman G.E., Ollmann M.M., Barsh G.S., Sakurai T., Yanagisawa M., and Elmquist J.K. Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area. J. Comp. Neurol. 402 (1998) 442-459
51. Elmquist J.K., Bjørbaek C., Ahima R.S., Flier J.S., and Saper C.B. Distributions of leptin receptor mRNA isoforms in the rat brain. J. Comp. Neurol. 395 (1998) 535-547
52. Erickson J.C., Clegg K.E., and Palmiter R.D. Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y. Nature 381 (1996) 415-421
53. Fadel J., and Deutch A.Y. Anatomical substrates of orexin-dopamine interactions: lateral hypothalamic projections to the ventral tegmental area. Neuroscience 111 (2002) 379-387
54. Fan W., Boston B.A., Kesterson R.A., Hruby V.J., and Cone R.D. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature 385 (1997) 165-168
55. Figlewicz D.P., Evans S.B., Murphy J., Hoen M., and Baskin D.G. Expression of receptors for insulin and leptin in the ventral tegmental area/substantia nigra (VTA/SN) of the rat. Brain Res. 964 (2003) 107-115
56. Figlewicz D.P., MacDonald Naleid A., and Sipols A.J. Modulation of food reward by adiposity signals. Physiol. Behav. 91 (2007) 473-478
57. Figlewicz D.P., Szot P., Chavez M., Woods S.C., and Veith R.C. Intraventricular insulin increases dopamine transporter mRNA in rat VTA/substantia nigra. Brain Res. 644 (1994) 331-334
58. Fulton S., Pissios P., Manchon R.P., Stiles L., Frank L., Pothos E.N., Maratos-Flier E., and Flier J.S. Leptin regulation of the mesoaccumbens dopamine pathway. Neuron 51 (2006) 811-822
59. Gahtan E., Auerbach J.M., Groner Y., and Segal M. Reversible impairment of long-term potentiation in transgenic Cu/Zn-SOD mice. Eur. J. Neurosci. 10 (1998) 538-544
60. Gao Q., and Horvath T.L. Neurobiology of feeding and energy expenditure. Ann. Rev. Neurosci. 30 (2007) 367-398
61. Gao S., Kinzig K.P., Aja S., Scott K.A., Keung W., Kelly S., Strynadka K., Chohnan S., Smith W.W., Tamashiro K.L., Ladenheim E.E., Ronnett G.V., Tu Y., Birnbaum M.J., Lopaschuk G.D., and Moran T.H. Leptin activates hypothalamic acetyl-CoA carboxylase to inhibit food intake. Proc. Natl. Acad. Sci. USA 104 (2007) 17358-17363
62. Gao Q., Wolfgang M.J., Neschen S., Morino K., Horvath T.L., Shulman G.I., and Fu X.Y. Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation. Proc. Natl. Acad. Sci. USA 101 (2004) 4661-4666
63. Garcia B.G., Wei Y., Moron J.A., Lin R.Z., Javitch J.A., and Galli A. Akt is essential for insulin modulation of amphetamine-induced human dopamine transporter cell-surface redistribution. Mol. Pharmacol. 68 (2005) 102-109
64. Gong L., Yao F., Hockman K., Heng H.H., Morton G.J., Takeda K., Akira S., Low M.J., Rubinstein M., and MacKenzie R.G. Signal transducer and activator of transcription-3 is required in hypothalamic agouti-related protein/neuropeptide Y neurons for normal energy homeostasis. Endocrinology 149 (2008) 3346-3354
65. Gómez-Pinilla F. Brain foods: the effects of nutrients on brain function. Nat. Rev. Neurosci. 9 (2008) 568-578
66. Gropp E., Shanabrough M., Borok E., Xu A.W., Janoschek R., Buch T., Plum L., Balthasar N., Hampel B., Waisman A., Barsh G.S., Horvath T.L., and Brüning J.C. Agouti-related peptide-expressing neurons are mandatory for feeding. Nat. Neurosci. 8 (2005) 1289-1291
67. Gutiérrez-Juárez R., Obici S., and Rossetti L. Melanocortin-independent effects of leptin on hepatic glucose fluxes. J. Biol. Chem. 279 (2004) 49704-49715
68. Halliwell B., and Whiteman M. Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean?. Brit. J. Pharmacol. 142 (2004) 231-255
69. Harris G.C., Wimmer M., and Aston-Jones G. A role for lateral hypothalamic orexin neurons in reward seeking. Nature 437 (2005) 556-559
70. Harrold J.A., Widdowson P.S., and Williams G. 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. Diabetes 48 (1999) 267-271
71. Haskell-Luevano C., and Monck E.K. Agouti-related protein functions as an inverse agonist at a constitutively active brain melanocortin-4 receptor. Regul. Pept. 99 (2001) 1-7
72. Havrankova J., Roth J., and Brownstein M. Insulin receptors are widely distributed in the central nervous system of the rat. Nature 272 (1978) 827-829
73. Heimer L., Zahm D.S., Churchill L., Kalivas P.W., and Wohltmann C. Specificity in the projection patterns of accumbal core and shell in the rat. Neuroscience 41 (1991) 89-125
74. Hentges S.T., Nishiyama M., Overstreet L.S., Stenzel-Poore M., Williams J.T., and Low M.J. GABA release from proopiomelanocortin neurons. J. Neurosci. 24 (2004) 1578-1583
75. Hetherington A.W., and Ranson S.W. Hypothalamic lesions and adiposity in the rat. Anat. Rec. 78 (1940) 149-172
76. Heymsfield S.B., Greenberg A.S., Fujioka K., Dixon R.M., Kushner R., Hunt T., Lubina J.A., Patane J., Self B., Hunt P., and McCamish M. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 282 (1999) 1568-1575
77. Himmi T., Boyer A., and Orsini J.C. Changes in lateral hypothalamic neuronal activity accompanying hyper- and hypo-glycemias. Physiol. Behav. 44 (1988) 347-354
78. Hnasko T.S., Szczypka M.S., Alaynick W.A., During M.J., and Palmiter R.D. A role for dopamine in feeding responses produced by orexigenic agents. Brain Res. 1023 (2004) 309-318
79. Hommel J.D., Trinko R., Sears R.M., Georgescu D., Liu Z.W., Gao X.B., Thurmon J.J., Marinelli M., and DiLeone R.J. Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Neuron 51 (2006) 801-810
80. Horvath T.L., Andrews Z.B., and Diano S. Fuel utilization by hypothalamic neurons: roles for ROS. Trends Endocrinol. Metab. (2008)
81. Horvath T.L., Bechmann I., Naftolin F., Kalra S.P., and Leranth C. Heterogeneity in the neuropeptide Y-containing neurons of the rat arcuate nucleus: GABAergic and non-GABAergic subpopulations. Brain Res. 756 (1997) 283-286
82. Horvath T.L., Diano S., and van den Pol A.N. Synaptic interaction between hypocretin (orexin) and neuropeptide Y cells in the rodent and primate hypothalamus: a novel circuit implicated in metabolic and endocrine regulations. J. Neurosci. 19 (1999) 1072-1087
83. Hyman S.E., Malenka R.C., and Nestler E.J. Neural mechanisms of addiction: the role of reward-related learning and memory. Ann. Rev. Neurosci. (2006)
84. Ibrahim N., Bosch M.A., Smart J.L., Qiu J., Rubinstein M., Rønnekleiv O.K., Low M.J., and Kelly M.J. Hypothalamic proopiomelanocortin neurons are glucose responsive and express K(ATP) channels. Endocrinology 144 (2003) 1331-1340
85. Ingraham H.A., Lala D.S., Ikeda Y., Luo X., Shen W.H., Nachtigal M.W., Abbud R., Nilson J.H., and Parker K.L. The nuclear receptor steroidogenic factor 1 acts at multiple levels of the reproductive axis. Genes Dev. 8 (1994) 2302-2312
86. Inoue H., Ogawa W., Asakawa A., Okamoto Y., Nishizawa A., Matsumoto M., Teshigawara K., Matsuki Y., Watanabe E., Hiramatsu R., Notohara K., Katayose K., Okamura H., Kahn C.R., Noda T., Takeda K., Akira S., Inui A., and Kasuga M. Role of hepatic STAT3 in brain-insulin action on hepatic glucose production. Cell Metab. 3 (2006) 267-275
87. Jaber M., Jones S., Giros B., and Caron M.G. The dopamine transporter: a crucial component regulating dopamine transmission. Mov. Disord. 12 (1997) 629-633
88. Janoschek R., Plum L., Koch L., Münzberg H., Diano S., Shanabrough M., Müller W., Horvath T.L., and Brüning J.C. gp130 signaling in proopiomelanocortin neurons mediates the acute anorectic response to centrally applied ciliary neurotrophic factor. Proc. Natl. Acad. Sci. USA 103 (2006) 10707-10712
89. Jewett D.C., Cleary J., Levine A.S., Schaal D.W., and Thompson T. Effects of neuropeptide Y, insulin, 2-deoxyglucose, and food deprivation on food-motivated behavior. Psychopharmacology (Berl) 120 (1995) 267-271
90. Kalivas P.W., and Volkow N.D. The neural basis of addiction: a pathology of motivation and choice. Am. J. Psychiatry 162 (2005) 1403-1413
91. Katafuchi T., Oomura Y., and Yoshimatsu H. Single neuron activity in the rat lateral hypothalamus during 2-deoxy-D-glucose induced and natural feeding behavior. Brain Res. 359 (1985) 1-9
92. Kim M.S., Pak Y.K., Jang P.G., Namkoong C., Choi Y.S., Won J.C., Kim K.S., Kim S.W., Kim H.S., Park J.Y., Kim Y.B., and Lee K.U. Role of hypothalamic Foxo1 in the regulation of food intake and energy homeostasis. Nat. Neurosci. 9 (2006) 901-906
93. Kitamura T., Feng Y., Kitamura Y.I., Chua S.C., Xu A.W., Barsh G.S., Rossetti L., and Accili D. Forkhead protein FoxO1 mediates Agrp-dependent effects of leptin on food intake. Nat. Med. 12 (2006) 534-540
94. Koch L., Wunderlich F.T., Seibler J., Könner A.C., Hampel B., Irlenbusch S., Brabant G., Kahn C.R., Schwenk F., and Brüning J.C. Central insulin action regulates peripheral glucose and fat metabolism in mice. J. Clin. Invest. 118 (2008) 2132-2147
95. Kohn A.D., Kovacina K.S., and Roth R.A. Insulin stimulates the kinase activity of RAC-PK, a pleckstrin homology domain containing ser/thr kinase. EMBO J. 14 (1995) 4288-4295
96. Kokoeva M.V., Yin H., and Flier J.S. Neurogenesis in the hypothalamus of adult mice: potential role in energy balance. Science 310 (2005) 679-683
97. Komori T., Morikawa Y., Nanjo K., and Senba E. Induction of brain-derived neurotrophic factor by leptin in the ventromedial hypothalamus. Neuroscience 139 (2006) 1107-1115
98. Kovacev V.P. Effect of hormones on fatty acid release by rat adipose tissue in vivo. Am. J. Physiol. 210 (1966) 1199-1208
99. Könner A.C., Janoschek R., Plum L., Jordan S.D., Rother E., Ma X., Xu C., Enriori P., Hampel B., Barsh G.S., Kahn C.R., Cowley M.A., Ashcroft F.M., and Brüning J.C. Insulin action in AgRP-expressing neurons is required for suppression of hepatic glucose production. Cell Metab. 5 (2007) 438-449
100. Lage R., Diéguez C., Vidal-Puig A., and López M. AMPK: a metabolic gauge regulating whole-body energy homeostasis. Trends Mol. Med. 14 (2008) 539-549
101. Lala D.S., Rice D.A., and Parker K.L. Steroidogenic factor I, a key regulator of steroidogenic enzyme expression, is the mouse homolog of fushi tarazu-factor I. Mol. Endocrinol. 6 (1992) 1249-1258
102. Lam T.K., Schwartz G.J., and Rossetti L. Hypothalamic sensing of fatty acids. Nat. Neurosci. 8 (2005) 579-584
103. Lane M.D., Wolfgang M., Cha S.H., and Dai Y. Regulation of food intake and energy expenditure by hypothalamic malonyl-CoA. Int. J. Obes. (Lond) 32 Suppl 4 (2008) S49-S54
104. Langhans W. Fatty acid oxidation in the energostatic control of eating - a new idea. Appetite 51 (2008) 446-451
105. Lavis V.R., and Williams R.H. Lipolytic effects of high concentrations of insulin on isolated fat cells. Enhancement of the response to lipolytic hormones. Diabetes 22 (1973) 629-636
106. de Lecea L., Kilduff T.S., Peyron C., Gao X., Foye P.E., Danielson P.E., Fukuhara C., Battenberg E.L., Gautvik V.T., Bartlett II F.S., Frankel W.N., Van del Pol A.N., Bloom F.E., Gautvik K.M., and Sutcliffe J.G. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc. Natl. Acad. Sci. USA 95 (1998) 322-327
107. Lee Y.S., Challis B.G., Thompson D.A., Yeo G.S., Keogh J.M., Madonna M.E., Wraight V., Sims M., Vatin V., Meyre D., Shield J., Burren C., Ibrahim Z., Cheetham T., Swift P., Blackwood A., Hung C.C., Wareham N.J., Froguel P., Millhauser G.L., O'Rahilly S., and Farooqi I.S. A POMC variant implicates beta-melanocyte-stimulating hormone in the control of human energy balance. Cell Metab. 3 (2006) 135-140
108. Leibel R.L., Rosenbaum M., and Hirsch J. Changes in energy expenditure resulting from altered body weight. New Engl. J. Med. 332 (1995) 621-628
109. Leloup C., Magnan C., Benani A., Bonnet E., Alquier T., Offer G., Carriere A., Périquet A., Fernandez Y., Ktorza A., Casteilla L., and Pénicaud L. Mitochondrial reactive oxygen species are required for hypothalamic glucose sensing. Diabetes 55 (2006) 2084-2090
110. Lepore M., Vorel S.R., Lowinson J., and Gardner E.L. Conditioned place preference induced by delta 9-tetrahydrocannabinol: comparison with cocaine, morphine, and food reward. Life Sci. 56 (1995) 2073-2080
111. Levin B.E., Routh V.H., Kang L., Sanders N.M., and Dunn-Meynell A.A. Neuronal glucosensing: what do we know after 50 years?. Diabetes 53 (2004) 2521-2528
112. Li Y.Z., and Davidowa H. Food deprivation decreases responsiveness of ventromedial hypothalamic neurons to melanocortins. J. Neurosci. Res. 77 (2004) 596-602
113. Liu L., Karkanias G.B., Morales J.C., Hawkins M., Barzilai N., Wang J., and Rossetti L. Intracerebroventricular leptin regulates hepatic but not peripheral glucose fluxes. J. Biol. Chem. 273 (1998) 31160-31167
114. Lopez-Valpuesta F.J., Nyce J.W., Griffin-Biggs T.A., Ice J.C., and Myers R.D. Antisense to NPY-Y1 demonstrates that Y1 receptors in the hypothalamus underlie NPY hypothermia and feeding in rats. Proc. Biol. Sci. 263 (1996) 881-886
115. López M., Lage R., Saha A.K., Pérez-Tilve D., Vázquez M.J., Varela L., Sangiao-Alvarellos S., Tovar S., Raghay K., Rodríguez-Cuenca S., Deoliveira R.M., Castañeda T., Datta R., Dong J.Z., Culler M., Sleeman M.W., Alvarez C.V., Gallego R., Lelliott C.J., Carling D., Tschöp M.H., Diéguez C., and Vidal-Puig A. Hypothalamic fatty acid metabolism mediates the orexigenic action of ghrelin. Cell Metab. 7 (2008) 389-399
116. López M., Lelliott C.J., and Vidal-Puig A. Hypothalamic fatty acid metabolism: a housekeeping pathway that regulates food intake. Bioessays 29 (2007) 248-261
117. López M., and Vidal-Puig A. Brain lipogenesis and regulation of energy metabolism. Curr. Opin. Clin. Nutr. Metab. Care 11 (2008) 483-490
118. de Luca C., Kowalski T.J., Zhang Y., Elmquist J.K., Lee C., Kilimann M.W., Ludwig T., Liu S.M., and Chua S.C. Complete rescue of obesity, diabetes, and infertility in db/db mice by neuron-specific LEPR-B transgenes. J. Clin. Invest. 115 (2005) 3484-3493
119. Luo X., Ikeda Y., and Parker K.L. A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation. Cell 77 (1994) 481-490
120. Luquet S., Perez F.A., Hnasko T.S., and Palmiter R.D. NPY/AgRP neurons are essential for feeding in adult mice but can be ablated in neonates. Science 310 (2005) 683-685
121. MacGregor G.G., Dong K., Vanoye C.G., Tang L., Giebisch G., and Hebert S.C. Nucleotides and phospholipids compete for binding to the C terminus of KATP channels. Proc. Natl. Acad. Sci. USA 99 (2002) 2726-2731
122. Majdic G., Young M., Gomez-Sanchez E., Anderson P., Szczepaniak L.S., Dobbins R.L., McGarry J.D., and Parker K.L. Knockout mice lacking steroidogenic factor 1 are a novel genetic model of hypothalamic obesity. Endocrinology 143 (2002) 607-614
123. Margolis R.U., and Altszuler N. Insulin in the cerebrospinal fluid. Nature 215 (1967) 1375-1376
124. Marsh D.J., Weingarth D.T., Novi D.E., Chen H.Y., Trumbauer M.E., Chen A.S., Guan X.M., Jiang M.M., Feng Y., Camacho R.E., Shen Z., Frazier E.G., Yu H., Metzger J.M., Kuca S.J., Shearman L.P., Gopal-Truter S., MacNeil D.J., Strack A.M., MacIntyre D.E., van der Ploeg L.H., and Qian S. Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism. Proc. Natl. Acad. Sci. USA 99 (2002) 3240-3245
125. Matsumoto M., Ogawa W., Hino Y., Furukawa K., Ono Y., Takahashi M., Ohba M., Kuroki T., and Kasuga M. Inhibition of insulin-induced activation of Akt by a kinase-deficient mutant of the epsilon isozyme of protein kinase C. J. Biol. Chem. 276 (2001) 14400-14406
126. Mayer J. Glucostatic mechanism of regulation of food intake. New Engl. J. Med. 249 (1953) 13-16
127. McCrimmon R.J., Shaw M., Fan X., Cheng H., Ding Y., Vella M.C., Zhou L., McNay E.C., and Sherwin R.S. Key role for AMP-activated protein kinase in the ventromedial hypothalamus in regulating counterregulatory hormone responses to acute hypoglycemia. Diabetes 57 (2008) 444-450
128. McGowan M.K., Andrews K.M., Fenner D., and Grossman S.P. Chronic intrahypothalamic insulin infusion in the rat: behavioral specificity. Physiol. Behav. 54 (1993) 1031-1034
129. Mercer J.G., Hoggard N., Williams L.M., Lawrence C.B., Hannah L.T., and Trayhurn P. Localization of leptin receptor mRNA and the long form splice variant (Ob-Rb) in mouse hypothalamus and adjacent brain regions by in situ hybridization. FEBS Lett. 387 (1996) 113-116
130. Mesaros A., Koralov S.B., Rother E., Wunderlich F.T., Ernst M.B., Barsh G.S., Rajewsky K., and Brüning J.C. Activation of Stat3 signaling in AgRP neurons promotes locomotor activity. Cell Metab. 7 (2008) 236-248
131. Miller J.C., Gnaedinger J.M., and Rapoport S.I. Utilization of plasma fatty acid in rat brain: distribution of [14C]palmitate between oxidative and synthetic pathways. J. Neurochem. 49 (1987) 1507-1514
132. Minokoshi Y., Alquier T., Furukawa N., Kim Y.B., Lee A., Xue B., Mu J., Foufelle F., Ferré P., Birnbaum M.J., Stuck B.J., and Kahn B.B. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 428 (2004) 569-574
133. Morton G.J., Cummings D.E., Baskin D.G., Barsh G.S., and Schwartz M.W. Central nervous system control of food intake and body weight. Nature 443 (2006) 289-295
134. Morton G.J., Gelling R.W., Niswender K.D., Morrison C.D., Rhodes C.J., and Schwartz M.W. Leptin regulates insulin sensitivity via phosphatidylinositol-3-OH kinase signaling in mediobasal hypothalamic neurons. Cell Metab. 2 (2005) 411-420
135. Muroya S., Yada T., Shioda S., and Takigawa M. Glucose-sensitive neurons in the rat arcuate nucleus contain neuropeptide Y. Neurosci. Lett. 264 (1999) 113-116
136. Nestler E.J. Is there a common molecular pathway for addiction?. Nat. Neurosci. 8 (2005) 1445-1449
137. Nicola S.M., Surmeier J., and Malenka R.C. Dopaminergic modulation of neuronal excitability in the striatum and nucleus accumbens. Ann. Rev. Neurosci. 23 (2000) 185-215
138. Nijenhuis W.A., Oosterom J., and Adan R.A. AgRP(83-132) acts as an inverse agonist on the human-melanocortin-4 receptor. Mol. Endocrinol. 15 (2001) 164-171
139. Niswender K.D., Morrison C.D., Clegg D.J., Olson R., Baskin D.G., Myers M.G., Seeley R.J., and Schwartz M.W. Insulin activation of phosphatidylinositol 3-kinase in the hypothalamic arcuate nucleus: a key mediator of insulin-induced anorexia. Diabetes 52 (2003) 227-231
140. Niswender K.D., Morton G.J., Stearns W.H., Rhodes C.J., Myers M.G., and Schwartz M.W. Intracellular signalling. Key enzyme in leptin-induced anorexia. Nature 413 (2001) 794-795
141. Obici S., Zhang B.B., Karkanias G., and Rossetti L. Hypothalamic insulin signaling is required for inhibition of glucose production. Nat. Med. 8 (2002) 1376-1382
142. Ollmann M.M., Wilson B.D., Yang Y.K., Kerns J.A., Chen Y., Gantz I., and Barsh G.S. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 278 (1997) 135-138
143. Oomura Y., and Yoshimatsu H. Neural network of glucose monitoring system. J. Auton. Nerv. Syst. 10 (1984) 359-372
144. Overton P.G., and Clark D. Burst firing in midbrain dopaminergic neurons. Brain Res. Brain Res. Rev. 25 (1997) 312-334
145. Parker K.L., and Schimmer B.P. Steroidogenic factor 1: a key determinant of endocrine development and function. Endocr. Rev. 18 (1997) 361-377
146. Parton L.E., Ye C.P., Coppari R., Enriori P.J., Choi B., Zhang C.Y., Xu C., Vianna C.R., Balthasar N., Lee C.E., Elmquist J.K., Cowley M.A., and Lowell B.B. Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature 449 (2007) 228-232
147. Patterson T.A., Brot M.D., Zavosh A., Schenk J.O., Szot P., and Figlewicz D.P. Food deprivation decreases mRNA and activity of the rat dopamine transporter. Neuroendocrinology 68 (1998) 11-20
148. Peyron C., Tighe D.K., van der Pol A.N., de Lecea L., Heller H.C., Sutcliffe J.G., and Kilduff T.S. Neurons containing hypocretin (orexin) project to multiple neuronal systems. J. Neurosci. 18 (1998) 9996-10015
149. Pinto S., Roseberry A.G., Liu H., Diano S., Shanabrough M., Cai X., Friedman J.M., and Horvath T.L. Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science 304 (2004) 110-115
150. Plum L., Belgardt B.F., and Brüning J.C. Central insulin action in energy and glucose homeostasis. J. Clin. Invest. 116 (2006) 1761-1766
151. Plum L., Ma X., Hampel B., Balthasar N., Coppari R., Münzberg H., Shanabrough M., Burdakov D., Rother E., Janoschek R., Alber J., Belgardt B.F., Koch L., Seibler J., Schwenk F., Fekete C., Suzuki A., Mak T.W., Krone W., Horvath T.L., Ashcroft F.M., and Brüning J.C. Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity. J. Clin. Invest. 116 (2006) 1886-1901
152. Plum L., Rother E., Münzberg H., Wunderlich F.T., Morgan D.A., Hampel B., Shanabrough M., Janoschek R., Könner A.C., Alber J., Suzuki A., Krone W., Horvath T.L., Rahmouni K., and Brüning J.C. Enhanced leptin-stimulated Pi3k activation in the CNS promotes white adipose tissue transdifferentiation. Cell Metab. 6 (2007) 431-445
153. Pocai A., Lam T.K., Gutierrez-Juarez R., Obici S., Schwartz G.J., Bryan J., Aguilar-Bryan L., and Rossetti L. Hypothalamic K(ATP) channels control hepatic glucose production. Nature 434 (2005) 1026-1031
154. Qian S., Chen H., Weingarth D., Trumbauer M.E., Novi D.E., Guan X., Yu H., Shen Z., Feng Y., Frazier E., Chen A., Camacho R.E., Shearman L.P., Gopal-Truter S., MacNeil D.J., Van der Ploeg L.H., and Marsh D.J. Neither agouti-related protein nor neuropeptide Y is critically required for the regulation of energy homeostasis in mice. Mol. Cell. Biol. 22 (2002) 5027-5035
155. Qu D., Ludwig D.S., Gammeltoft S., Piper M., Pelleymounter M.A., Cullen M.J., Mathes W.F., Przypek R., Kanarek R., and Maratos-Flier E. A role for melanin-concentrating hormone in the central regulation of feeding behaviour. Nature 380 (1996) 243-247
156. Rapoport S.I. In vivo labeling of brain phospholipids by long-chain fatty acids: relation to turnover and function. Lipids 31 Suppl (1996) S97-101
157. Rezek M. The role of insulin in the glucostatic control of food intake. Can. J. Physiol. Pharmacol. 54 (1976) 650-665
158. Rossetti L., Massillon D., Barzilai N., Vuguin P., Chen W., Hawkins M., Wu J., and Wang J. Short term effects of leptin on hepatic gluconeogenesis and in vivo insulin action. J. Biol. Chem. 272 (1997) 27758-27763
159. Rossi M., Choi S.J., O'Shea D., Miyoshi T., Ghatei M.A., and Bloom S.R. Melanin-concentrating hormone acutely stimulates feeding, but chronic administration has no effect on body weight. Endocrinology 138 (1997) 351-355
160. Rother E., Könner A.C., and Brüning J.C. Neurocircuits integrating hormone and nutrient signaling in control of glucose metabolism. Am. J. Physiol. Endocrinol. Metab. 294 (2008) E810-E816
161. Safiulina V.F., Afzalov R., Khiroug L., Cherubini E., and Giniatullin R. Reactive oxygen species mediate the potentiating effects of ATP on GABAergic synaptic transmission in the immature hippocampus. J. Biol. Chem. 281 (2006) 23464-23470
162. Sahm U.G., Qarawi M.A., Olivier G.W., Ahmed A.R., Branch S.K., Moss S.H., and Pouton C.W. The melanocortin (MC3) receptor from rat hypothalamus: photoaffinity labelling and binding of alanine-substituted alpha-MSH analogues. FEBS Lett. 350 (1994) 29-32
163. Sakurai T., Amemiya A., Ishii M., Matsuzaki I., Chemelli R.M., Tanaka H., Williams S.C., Richarson J.A., Kozlowski G.P., Wilson S., Arch J.R., Buckingham R.E., Haynes A.C., Carr S.A., Annan R.S., McNulty D.E., Liu W.S., Terrett J.A., Elshourbagy N.A., Bergsma D.J., and Yanagisawa M. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92 (1998) (1 page following 696)
164. Sakurai T. The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat. Rev. Neurosci. 8 (2007) 171-181
165. Schultz W. Predictive reward signal of dopamine neurons. J. Neurophysiol. 80 (1998) 1-27
166. Schultz W. Getting formal with dopamine and reward. Neuron 36 (2002) 241-263
167. Schwartz M.W., Woods S.C., Porte D., Seeley R.J., and Baskin D.G. Central nervous system control of food intake. Nature 404 (2000) 661-671
168. Schwartz M.W. Inhibition of hypothalamic neuropeptide Y gene expression by insulin. Endocrinology 130 (1992) 3608-3616
169. Seaquist E.R., Damberg G.S., Tkac I., and Gruetter R. The effect of insulin on in vivo cerebral glucose concentrations and rates of glucose transport/metabolism in humans. Diabetes 50 (2001) 2203-2209
170. Seeley R.J., and Woods S.C. Monitoring of stored and available fuel by the CNS: implications for obesity. Nat. Rev. Neurosci. 4 (2003) 901-909
171. Seeley R.J., Yagaloff K.A., Fisher S.L., Burn P., Thiele T.E., van Dijk G., Baskin D.G., and Schwartz M.W. Melanocortin receptors in leptin effects. Nature 390 (1997) 349
172. Shimada M., Tritos N.A., Lowell B.B., Flier J.S., and Maratos-Flier E. Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature 396 (1998) 670-674
173. Shinoda K., Lei H., Yoshii H., Nomura M., Nagano M., Shiba H., Sasaki H., Osawa Y., Ninomiya Y., and Niwa O. Developmental defects of the ventromedial hypothalamic nucleus and pituitary gonadotroph in the Ftz-F1 disrupted mice. Dev. Dynam. 204 (1995) 22-29
174. Shyng S.L., and Nichols C.G. Membrane phospholipid control of nucleotide sensitivity of KATP channels. Science 282 (1998) 1138-1141
175. Sierra A.Y., Gratacós E., Carrasco P., Clotet J., Ureña J., Serra D., Asins G., Hegardt F.G., and Casals N. CPT1c is localized in endoplasmic reticulum of neurons and has carnitine palmitoyltransferase activity. J. Biol. Chem. 283 (2008) 6878-6885
176. Sipols A.J., Baskin D.G., and Schwartz M.W. Effect of intracerebroventricular insulin infusion on diabetic hyperphagia and hypothalamic neuropeptide gene expression. Diabetes 44 (1995) 147-151
177. Skofitsch G., Jacobowitz D.M., and Zamir N. Immunohistochemical localization of a melanin concentrating hormone-like peptide in the rat brain. Brain Res. Bull. 15 (1985) 635-649
178. Smyth S., and Heron A. Diabetes and obesity: the twin epidemics. Nat. Med. 12 (2006) 75-80
179. Sokoloff L., Reivich M., Kennedy C., Des Rosiers M.H., Patlak C.S., Pettigrew K.D., Sakurada O., and Shinohara M. The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J. Neurochem. 28 (1977) 897-916
180. Spanswick D., Smith M.A., Mirshamsi S., Routh V.H., and Ashford M.L. Insulin activates ATP-sensitive K+ channels in hypothalamic neurons of lean, but not obese rats. Nat. Neurosci. 3 (2000) 757-758
181. Sternson S.M., Shepherd G.M., and Friedman J.M. Topographic mapping of VMH arcuate nucleus microcircuits and their reorganization by fasting. Nat. Neurosci. 8 (2005) 1356-1363
182. Stratford T.R., and Kelley A.E. Evidence of a functional relationship between the nucleus accumbens shell and lateral hypothalamus subserving the control of feeding behavior. J. Neurosci. 19 (1999) 11040-11048
183. Strubbe J.H., and Mein C.G. Increased feeding in response to bilateral injection of insulin antibodies in the VMH. Physiol. Behav. 19 (1977) 309-313
184. Szczypka M.S., Rainey M.A., and Palmiter R.D. Dopamine is required for hyperphagia in Lep(ob/ob) mice. Nat. Genet. 25 (2000) 102-104
185. Teitelbaum P., and Epstein A.N. The lateral hypothalamic syndrome: recovery of feeding and drinking after lateral hypothalamic lesions. Psychol. Rev. 69 (1962) 74-90
186. Tejwani G.A., and Richard C.W. Effect of electrolytic and chemical ventromedial hypothalamic lesions on food intake, body weight, analgesia and the CNS opioid peptides in rats and mice. NIDA Res. Monogr. 75 (1986) 497-500
187. Thorens B. Glucose sensing and the pathogenesis of obesity and type 2 diabetes. Int. J. Obes. (Lond) 32 Suppl 6 (2008) S62-S71
188. Tolle V., and Low M.J. In vivo evidence for inverse agonism of Agouti-related peptide in the central nervous system of proopiomelanocortin-deficient mice. Diabetes 57 (2008) 86-94
189. Tong Q., Ye C.P., Jones J.E., Elmquist J.K., and Lowell B.B. Synaptic release of GABA by AgRP neurons is required for normal regulation of energy balance. Nat. Neurosci. 11 (2008) 998-1000
190. Tong Q., Ye C., McCrimmon R.J., Dhillon H., Choi B., Kramer M.D., Yu J., Yang Z., Christiansen L.M., Lee C.E., Choi C.S., Zigman J.M., Shulman G.I., Sherwin R.S., Elmquist J.K., and Lowell B.B. Synaptic glutamate release by ventromedial hypothalamic neurons is part of the neurocircuitry that prevents hypoglycemia. Cell Metab. 5 (2007) 383-393
191. Tritos N.A., Mastaitis J.W., Kokkotou E., and Maratos-Flier E. Characterization of melanin concentrating hormone and preproorexin expression in the murine hypothalamus. Brain Res. 895 (2001) 160-166
192. Unger J.W., Livingston J.N., and Moss A.M. Insulin receptors in the central nervous system: localization, signalling mechanisms and functional aspects. Prog. Neurobiol. 36 (1991) 343-362
193. Wang G.J., Volkow N.D., Logan J., Pappas N.R., Wong C.T., Zhu W., Netusil N., and Fowler J.S. Brain dopamine and obesity. Lancet 357 (2001) 354-357
194. Wang J.H., Wang F., Yang M.J., Yu D.F., Wu W.N., Liu J., Ma L.Q., Cai F., and Chen J.G. Leptin regulated calcium channels of neuropeptide Y and proopiomelanocortin neurons by activation of different signal pathways. Neuroscience 156 (2008) 89-98
195. Willie J.T., Chemelli R.M., Sinton C.M., and Yanagisawa M. To eat or to sleep? Orexin in the regulation of feeding and wakefulness. Ann. Rev. Neurosci. 24 (2001) 429-458
196. Winterbourn C.C. Reconciling the chemistry and biology of reactive oxygen species. Nat. Chem. Biol. 4 (2008) 278-286
197. Wise R.A. Brain reward circuitry: insights from unsensed incentives. Neuron 36 (2002) 229-240
198. Wisse B.E., Kim F., and Schwartz M.W. Physiology. An integrative view of obesity. Science 318 (2007) 928-929
199. Wolfgang M.J., Cha S.H., Sidhaye A., Chohnan S., Cline G., Shulman G.I., and Lane M.D. Regulation of hypothalamic malonyl-CoA by central glucose and leptin. Proc. Natl. Acad Sci. USA 104 (2007) 19285-19290
200. Wolfgang M.J., Kurama T., Dai Y., Suwa A., Asaumi M., Matsumoto S., Cha S.H., Shimokawa T., and Lane M.D. The brain-specific carnitine palmitoyltransferase-1c regulates energy homeostasis. Proc. Natl. Acad. Sci. USA 103 (2006) 7282-7287
201. Woods S.C., and D'Alessio D.A. Central control of body weight and appetite. J. Clin. Endocrinol. Metab. 93 (2008) S37-S50
202. Woods S.C., Seeley R.J., Porte D., and Schwartz M.W. Signals that regulate food intake and energy homeostasis. Science 280 (1998) 1378-1383
203. Woods S.C. Relationship between plasma and cerebrospinal fluid insulin levels of dogs. Am. J. Physiol. - Endocrinol. Metabol. 233 (1977) 331-334
204. Wullschleger S., Loewith R., and Hall M.N. TOR signaling in growth and metabolism. Cell 124 (2006) 471-484
205. Xu B., Goulding E.H., Zang K., Cepoi D., Cone R.D., Jones K.R., Tecott L.H., and Reichardt L.F. Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat. Neurosci. 6 (2003) 736-742
206. Xu A.W., Kaelin C.B., Takeda K., Akira S., Schwartz M.W., and Barsh G.S. PI3K integrates the action of insulin and leptin on hypothalamic neurons. J. Clin. Invest. 115 (2005) 951-958
207. Xu A.W., Ste-Marie L., Kaelin C.B., and Barsh G.S. Inactivation of signal transducer and activator of transcription 3 in proopiomelanocortin (Pomc) neurons causes decreased pomc expression, mild obesity, and defects in compensatory refeeding. Endocrinology 148 (2007) 72-80
208. Xue B., and Kahn B.B. AMPK integrates nutrient and hormonal signals to regulate food intake and energy balance through effects in the hypothalamus and peripheral tissues. J. Physiol. 574 (2006) 73-83
209. Zaborszky L., and Makara G.B. Intrahypothalamic connections: an electron microscopic study in the rat. Exp. Brain. Res. 34 (1979) 201-215
210. Zhang Y., Proenca R., Maffei M., Barone M., Leopold L., and Friedman J.M. Positional cloning of the mouse obese gene and its human homologue. Nature 372 (1994) 425-432
211. Zhou Q.Y., and Palmiter R.D. Dopamine-deficient mice are severely hypoactive, adipsic, and aphagic. Cell 83 (1995) 1197-1209