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Science China Life Sciences

, Volume 62, Issue 6, pp 771–790 | Cite as

An overview of energy and metabolic regulation

  • Song Wen
  • Chaoxun Wang
  • Min Gong
  • Ligang ZhouEmail author
Review

Abstract

The physiology and behaviors related to energy balance are monitored by the nervous and humoral systems. Because of the difficulty in treating diabetes and obesity, elucidating the energy balance mechanism and identifying critical targets for treatment are important research goals. Therefore, the purpose of this article is to describe energy regulation by the central nervous system (CNS) and peripheral humoral pathway. Homeostasis and rewarding are the basis of CNS regulation. Anorexigenic or orexigenic effects reflect the activities of the POMC/CART or NPY/AgRP neurons within the hypothalamus. Neurotransmitters have roles in food intake, and responsive brain nuclei have different functions related to food intake, glucose monitoring, reward processing. Peripheral gut- or adipose-derived hormones are the major source of peripheral humoral regulation systems. Nutrients or metabolites and gut microbiota affect metabolism via a discrete pathway. We also review the role of peripheral organs, the liver, adipose tissue, and skeletal muscle in peripheral regulation. We discuss these topics and how the body regulates metabolism.

Keywords

hedonic POMC/CART NPY/AgRP neurotransmitter brain nuclei gut-derived hormone gut microbiota BAT 

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Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (81370932), the United States MERCK IISP Fund (40313, 40309), Outstanding Leaders Training Program of Pudong Health Bureau of Shanghai (PWR12014-06), Integrative Medicine special fund of Shanghai Municipal Health Planning Committee (ZHYY-ZXYJHZX-2-201712) and the Key Studies (Special) Department Fund of the Pudong New Area Health Planning Commission (PWZzk2017-03).

References

  1. Adams, S.H. (2011). Emerging perspectives on essential amino acid metabolism in obesity and the insulin-resistant state. Adv Nutr 2, 445–456.Google Scholar
  2. Adamska, E., Ostrowska, L., Gorska, M., and Kretowski, A. (2014). The role of gastrointestinal hormones in the pathogenesis of obesity and type 2 diabetes. Prz Gastroenterol 9, 69–76.Google Scholar
  3. Adan, R.A.H., Vanderschuren, L.J.M.J., and la Fleur, S.E. (2008). Antiobesity drugs and neural circuits of feeding. Trends Pharmacol Sci 29, 208–217.Google Scholar
  4. Adeva, M.M., Calviño, J., Souto, G., and Donapetry, C. (2012). Insulin resistance and the metabolism of branched-chain amino acids in humans. Amino Acids 43, 171–181.Google Scholar
  5. Allen, S.S., Hatsukami, D., Brintnell, D.M., and Bade, T. (2005). Effect of nicotine replacement therapy on post-cessation weight gain and nutrient intake: a randomized controlled trial of postmenopausal female smokers. Addict Behav 30, 1273–1280.Google Scholar
  6. Anderson, E.J.P., Çakir, I., Carrington, S.J., Cone, R.D., Ghamari-Langroudi, M., Gillyard, T., Gimenez, L.E., and Litt, M.J. (2016). 60 YEARS OF POMC: regulation of feeding and energy homeostasis by a-MSH. J Mol Endocrinol 56, T157–T174.Google Scholar
  7. Arima, H., and Oiso, Y. (2010). Positive effect of baclofen on body weight reduction in obese subjects: a pilot study. Intern Med 49, 2043–2047.Google Scholar
  8. Arnone, M., Maruani, J., Chaperon, F., Thiébot, M.H., Poncelet, M., Soubrié, P., and Fur, G.L. (1997). Selective inhibition of sucrose and ethanol intake by SR 141716, an antagonist of central cannabinoid (CB1) receptors. Psychopharmacology 132, 104–106.Google Scholar
  9. Audrain-McGovern, J., and Benowitz, N.L. (2011). Cigarette smoking, nicotine, and body weight. Clin Pharmacol Ther 90, 164–168.Google Scholar
  10. Bäckhed, F., Manchester, J.K., Semenkovich, C.F., and Gordon, J.I. (2007). Mechanisms underlying the resistance to diet-induced obesity in germfree mice. Proc Natl Acad Sci USA 104, 979–984.Google Scholar
  11. Baggio, L.L., and Drucker, D.J. (2014). Glucagon-like peptide-1 receptors in the brain: controlling food intake and body weight. J Clin Invest 124, 4223–4226.Google Scholar
  12. Baik, J.H. (2013). Dopamine signaling in food addiction: role of dopamine D2 receptors. BMB Rep 46, 519–526.Google Scholar
  13. Bakshi, V.P., Newman, S.M., Smith-Roe, S., Jochman, K.A., and Kalin, N. H. (2007). Stimulation of lateral septum CRF2 receptors promotes anorexia and stress-like behaviors: functional homology to CRF1 receptors in basolateral amygdala. J Neurosci 27, 10568–10577.Google Scholar
  14. Batterham, R.L., Cowley, M.A., Small, C.J., Herzog, H., Cohen, M.A., Dakin, C.L., Wren, A.M., Brynes, A.E., Low, M.J., Ghatei, M.A., et al. (2002). Gut hormone PYY3-36 physiologically inhibits food intake. Nature 418, 650–654.Google Scholar
  15. Baver, S.B., Hope, K., Guyot, S., Bjorbaek, C., Kaczorowski, C., and O’Connell, K.M.S. (2014). Leptin modulates the intrinsic excitability of AgRP/NPY neurons in the arcuate nucleus of the hypothalamus. J Neurosci 34, 5486–5496.Google Scholar
  16. Beck, B. (2006). Neuropeptide Y in normal eating and in genetic and dietary-induced obesity. Philos Trans R Soc Lond B Biol Sci 361, 1159–1185.Google Scholar
  17. Beglinger, C., Degen, L., Matzinger, D., D’Amato, M., and Drewe, J. (2001). Loxiglumide, a CCK-A receptor antagonist, stimulates calorie intake and hunger feelings in humans. Am J Physiol Regul Integr Comp Physiol 280, R1149–R1154.Google Scholar
  18. Berridge, K.C., Ho, C.Y., Richard, J.M., and DiFeliceantonio, A.G. (2010). The tempted brain eats: pleasure and desire circuits in obesity and eating disorders. Brain Res 1350, 43–64.Google Scholar
  19. Bisaga, A., Danysz, W., and Foltin, R.W. (2008). Antagonism of glutamatergic NMDA and mGluR5 receptors decreases consumption of food in baboon model of binge-eating disorder. Eur Neuropsychopharmacol 18, 794–802.Google Scholar
  20. Björklund, A., and Dunnett, S.B. (2007). Dopamine neuron systems in the brain: an update. Trends Neurosci 30, 194–202.Google Scholar
  21. Bojanowska, E., and Ciosek, J. (2016). Can we selectively reduce appetite for energy-dense foods? An overview of pharmacological strategies for modification of food preference behavior. Curr Neuropharmacol 14, 118–142.Google Scholar
  22. Borgland, S.L., Chang, S.J., Bowers, M.S., Thompson, J.L., Vittoz, N., Floresco, S.B., Chou, J., Chen, B.T., and Bonci, A. (2009). Orexin A/hypocretin-1 selectively promotes motivation for positive reinforcers. J Neurosci 29, 11215–11225.Google Scholar
  23. Bradbury, M.J., Campbell, U., Giracello, D., Chapman, D., King, C., Tehrani, L., Cosford, N.D.P., Anderson, J., Varney, M.A., and Strack, A. M. (2005). Metabotropic glutamate receptor mGlu5 is a mediator of appetite and energy balance in rats and mice. J Pharmacol Exp Therapeut 313, 395–402.Google Scholar
  24. Brito, M.N., Brito, N.A., Baro, D.J., Song, C.K., and Bartness, T.J. (2007). Differential activation of the sympathetic innervation of adipose tissues by melanocortin receptor stimulation. Endocrinology 148, 5339–5347.Google Scholar
  25. Brown, J.A., Woodworth, H.L., and Leinninger, G.M. (2015). To ingest or rest? Specialized roles of lateral hypothalamic area neurons in coordinating energy balance. Front Syst Neurosci 9, 9.Google Scholar
  26. Brownley, K.A., Peat, C.M., La Via, M., and Bulik, C.M. (2015). Pharmacological approaches to the management of binge eating disorder. Drugs 75, 9–32.Google Scholar
  27. Cansell, C., Denis, R.G., Joly-Amado, A., Castel, J., and Luquet, S. (2012). Arcuate AgRP neurons and the regulation of energy balance. Front Endocrinol (Lausanne) 3, 169.Google Scholar
  28. Cardoso, F.L., Brites, D., and Brito, M.A. (2010). Looking at the bloodbrain barrier: molecular anatomy and possible investigation approaches. Brain Res Rev 64, 328–363.Google Scholar
  29. Challis, B.G., Yeo, G.S., Farooqi, I.S., Luan, J., Aminian, S., Halsall, D.J., Keogh, J.M., Wareham, N.J., and O’Rahilly, S. (2000). The CART gene and human obesity: mutational analysis and population genetics. Diabetes 49, 872–875.Google Scholar
  30. Chari, M., Lam, C.K.L., Wang, P.Y.T., and Lam, T.K.T. (2008). Activation of central lactate metabolism lowers glucose production in uncontrolled diabetes and diet-induced insulin resistance. Diabetes 57, 836–840.Google Scholar
  31. Chiolero, A., Faeh, D., Paccaud, F., and Cornuz, J. (2008). Consequences of smoking for body weight, body fat distribution, and insulin resistance. Am J Clin Nutr 87, 801–809.Google Scholar
  32. Chronwall, B.M. (1985). Anatomy and physiology of the neuroendocrine arcuate nucleus. Peptides 6 Suppl 2, 1–11.Google Scholar
  33. Cone, R.D. (2005). Anatomy and regulation of the central melanocortin system. Nat Neurosci 8, 571–578.Google Scholar
  34. Cooper, S.J., and Al-Naser, H.A. (2006). Dopaminergic control of food choice: contrasting effects of SKF 38393 and quinpirole on high-palatability food preference in the rat. Neuropharmacology 50, 953–963.Google Scholar
  35. Cota, D., Proulx, K., Smith, K.A.B., Kozma, S.C., Thomas, G., Woods, S. C., and Seeley, R.J. (2006). Hypothalamic mTOR signaling regulates food intake. Science 312, 927–930.Google Scholar
  36. Cotero, V.E., Zhang, B.B., and Routh, V.H. (2010). The response of glucose-excited neurones in the ventromedial hypothalamus to decreased glucose is enhanced in a murine model of type 2 diabetes mellitus. J Neuroendocrinol 22, 65–74.Google Scholar
  37. Covelo, I.R., Patel, Z.I., Luviano, J.A., Stratford, T.R., and Wirtshafter, D. (2014). Manipulation of GABA in the ventral pallidum, but not the nucleus accumbens, induces intense, preferential, fat consumption in rats. Behav Brain Res 270, 316–325.Google Scholar
  38. Cowley, M.A., Smart, J.L., Rubinstein, M., Cerdán, M.G., Diano, S., Horvath, T.L., Cone, R.D., and Low, M.J. (2001). Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411, 480–484.Google Scholar
  39. Cryer, P.E., Davis, S.N., and Shamoon, H. (2003). Hypoglycemia in diabetes. Diabetes Care 26, 1902–1912.Google Scholar
  40. D’Agostino, A.E. and Small, D.M. (2012). Neuroimaging the interaction of mind and metabolism in humans. Mol Metab 1(1–2), 10–20.Google Scholar
  41. Date, Y., Murakami, N., Toshinai, K., Matsukura, S., Niijima, A., Matsuo, H., Kangawa, K., and Nakazato, M. (2002). The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology 123, 1120–1128.Google Scholar
  42. De Backer, I., Hussain, S.S., Bloom, S.R., and Gardiner, J.V. (2016). Insights into the role of neuronal glucokinase. Am J Physiol Endocrinol Metab 311, E42–E55.Google Scholar
  43. de Clercq, N., Frissen, M.N., Groen, A.K., and Nieuwdorp, M. (2017). Gut microbiota and the gut-brain axis: new insights in the pathophysiology of metabolic syndrome. Psychosom Med 79, 874–879.Google Scholar
  44. De Vadder, F., Kovatcheva-Datchary, P., Goncalves, D., Vinera, J., Zitoun, C., Duchampt, A., Bäckhed, F., and Mithieux, G. (2014). Microbiotagenerated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156, 84–96.Google Scholar
  45. Droste, S.M., Saland, S.K., Schlitter, E.K., and Rodefer, J.S. (2010). AM 251 differentially effects food-maintained responding depending on food palatability. Pharmacol Biochem Behav 95, 443–448.Google Scholar
  46. Drucker, D.J. (2006). The biology of incretin hormones. Cell Metab 3, 153–165.Google Scholar
  47. Dunn-Meynell, A.A., Routh, V.H., Kang, L., Gaspers, L., and Levin, B.E. (2002). Glucokinase is the likely mediator of glucosensing in both glucose-excited and glucose-inhibited central neurons. Diabetes 51, 2056–2065.Google Scholar
  48. Egecioglu, E., Skibicka, K.P., Hansson, C., Alvarez-Crespo, M., Friberg, P. A., Jerlhag, E., Engel, J.A., and Dickson, S.L. (2011). Hedonic and incentive signals for body weight control. Rev Endocr Metab Disord 12, 141–151.Google Scholar
  49. Escartín-Pérez, R.E., Cendejas-Trejo, N.M., Cruz-Martínez, A.M., González-Hernández, B., Mancilla-Díaz, J.M., and Florán-Garduño, B. (2009). Role of cannabinoid CB1 receptors on macronutrient selection and satiety in rats. Physiol Behav 96, 646–650.Google Scholar
  50. Fan, W., Boston, B.A., Kesterson, R.A., Hruby, V.J., and Cone, R.D. (1997). Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature 385, 165–168.Google Scholar
  51. Febbraio, M.A., Hiscock, N., Sacchetti, M., Fischer, C.P., and Pedersen, B. K. (2004). Interleukin-6 is a novel factor mediating glucose homeostasis during skeletal muscle contraction. Diabetes 53, 1643–1648.Google Scholar
  52. Feifel, D., Goldenberg, J., Melendez, G., and Shilling, P.D. (2010). The acute and subchronic effects of a brain-penetrating, neurotensin-1 receptor agonist on feeding, body weight and temperature. Neuropharmacology 58, 195–198.Google Scholar
  53. Fioramonti, X., Marsollier, N., Song, Z., Fakira, K.A., Patel, R.M., Brown, S., Duparc, T., Pica-Mendez, A., Sanders, N.M., Knauf, C., et al. (2010). Ventromedial hypothalamic nitric oxide production is necessary for hypoglycemia detection and counterregulation. Diabetes 59, 519–528.Google Scholar
  54. Garfield, A.S., and Heisler, L.K. (2009). Pharmacological targeting of the serotonergic system for the treatment of obesity. J Physiol 587, 49–60.Google Scholar
  55. Geha, P.Y., Aschenbrenner, K., Felsted, J., O’Malley, S.S., and Small, D.M. (2013). Altered hypothalamic response to food in smokers. Am J Clin Nutr 97, 15–22.Google Scholar
  56. Goldstone, A.P., Prechtl, C.G., Scholtz, S., Miras, A.D., Chhina, N., Durighel, G., Deliran, S.S., Beckmann, C., Ghatei, M.A., Ashby, D.R., et al. (2014). Ghrelin mimics fasting to enhance human hedonic, orbitofrontal cortex, and hippocampal responses to food. Am J Clin Nutr 99, 1319–1330.Google Scholar
  57. Grandt, D., Schimiczek, M., Beglinger, C., Layer, P., Goebell, H., Eysselein, V.E., and Reeve Jr., J.R. (1994). Two molecular forms of Peptide YY (PYY) are abundant in human blood: characterization of a radioimmunoassay recognizing PYY 1–36 and PYY 3–36. Regul Pept 51, 151–159.Google Scholar
  58. Grill, H.J., and Hayes, M.R. (2012). Hindbrain neurons as an essential hub in the neuroanatomically distributed control of energy balance. Cell Metab 16, 296–309.Google Scholar
  59. Han, W., Tellez, L.A., Niu, J., Medina, S., Ferreira, T.L., Zhang, X., Su, J., Tong, J., Schwartz, G.J., van den Pol, A., et al. (2016). Striatal dopamine links gastrointestinal rerouting to altered sweet appetite. Cell Metab 23, 103–112.Google Scholar
  60. Hara, T., Kashihara, D., Ichimura, A., Kimura, I., Tsujimoto, G., and Hirasawa, A. (2014). Role of free fatty acid receptors in the regulation of energy metabolism. Biochim Biophys Acta 1841, 1292–1300.Google Scholar
  61. Harada, Y., Takayama, K., Ro, S., Ochiai, M., Noguchi, M., Iizuka, S., Hattori, T., and Yakabi, K. (2014). Urocortin1-induced anorexia is regulated by activation of the serotonin 2C receptor in the brain. Peptides 51, 139–144.Google Scholar
  62. Hartfield, A.W., Moore, N.A., and Clifton, P.G. (2003). Serotonergic and histaminergic mechanisms involved in intralipid drinking? Pharmacol Biochem Behav 76, 251–258.Google Scholar
  63. Hayes, D.J., and Greenshaw, A.J. (2011). 5-HT receptors and rewardrelated behaviour: a review. Neurosci Biobehav Rev 35, 1419–1449.Google Scholar
  64. Haynes, A.C., Jackson, B., Chapman, H., Tadayyon, M., Johns, A., Porter, R.A., and Arch, J.R.S. (2000). A selective orexin-1 receptor antagonist reduces food consumption in male and female rats. Regul Pept 96, 45–51.Google Scholar
  65. Heisler, L.K., Jobst, E.E., Sutton, G.M., Zhou, L., Borok, E., Thornton-Jones, Z., Liu, H.Y., Zigman, J.M., Balthasar, N., Kishi, T., et al. (2006). Serotonin reciprocally regulates melanocortin neurons to modulate food intake. Neuron 51, 239–249.Google Scholar
  66. Henao-Mejia, J., Elinav, E., Jin, C., Hao, L., Mehal, W.Z., Strowig, T., Thaiss, C.A., Kau, A.L., Eisenbarth, S.C., Jurczak, M.J., et al. (2012). Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482, 179–185.Google Scholar
  67. Hensler, J.G. (2006). Serotonergic modulation of the limbic system. Neurosci Biobehav Rev 30, 203–214.Google Scholar
  68. 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. (2006). Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Neuron 51, 801–810.Google Scholar
  69. Horder, J., Harmer, C.J., Cowen, P.J., and McCabe, C. (2010). Reduced neural response to reward following 7 days treatment with the cannabinoid CB1 antagonist rimonabant in healthy volunteers. Int J Neuropsychopharmacol 13, 1103–1113.Google Scholar
  70. Hoyda, T.D., Samson, W.K., and Ferguson, A.V. (2009). Adiponectin depolarizes parvocellular paraventricular nucleus neurons controlling neuroendocrine and autonomic function. Endocrinology 150, 832–840.Google Scholar
  71. Huo, L., Maeng, L., Bjørbaek, C., and Grill, H.J. (2007). Leptin and the control of food intake: neurons in the nucleus of the solitary tract are activated by both gastric distension and leptin. Endocrinology 148, 2189–2197.Google Scholar
  72. Huszar, D., Lynch, C.A., Fairchild-Huntress, V., Dunmore, J.H., Fang, Q., Berkemeier, L.R., Gu, W., Kesterson, R.A., Boston, B.A., Cone, R.D., et al. (1997). Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88, 131–141.Google Scholar
  73. Huynh, M.K.Q., Kinyua, A.W., Yang, D.J., and Kim, K.W. (2016). Hypothalamic AMPK as a regulator of energy homeostasis. Neural Plasticity 2016, 1–12.Google Scholar
  74. Ikemoto, S. (2010). Brain reward circuitry beyond the mesolimbic dopamine system: a neurobiological theory. Neurosci BioBehav Rev 35, 129–150.Google Scholar
  75. Kamatchi, G.L., and Rathanaswami, P. (2012). Inhibition of deprivationinduced food intake by GABAA antagonists: roles of the hypothalamic, endocrine and alimentary mechanisms. J Clin Biochem Nutr 51, 19–26.Google Scholar
  76. Kamegai, J., Tamura, H., Shimizu, T., Ishii, S., Sugihara, H., and Wakabayashi, I. (2001). Chronic central infusion of ghrelin increases hypothalamic neuropeptide Y and Agouti-related protein mRNA levels and body weight in rats. Diabetes 50, 2438–2443.Google Scholar
  77. Kang, L., Dunn-Meynell, A.A., Routh, V.H., Gaspers, L.D., Nagata, Y., Nishimura, T., Eiki, J., Zhang, B.B., and Levin, B.E. (2006). Glucokinase is a critical regulator of ventromedial hypothalamic neuronal glucosensing. Diabetes 55, 412–420.Google Scholar
  78. Kanoski, S.E., Alhadeff, A.L., Fortin, S.M., Gilbert, J.R., and Grill, H.J. (2014). Leptin signaling in the medial nucleus tractus solitarius reduces food seeking and willingness to work for food. Neuropsychopharmacology 39, 605–613.Google Scholar
  79. Karlsson, F.H., Tremaroli, V., Nookaew, I., Bergström, G., Behre, C.J., Fagerberg, B., Nielsen, J., and Bäckhed, F. (2013). Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 498, 99–103.Google Scholar
  80. Katsurada, K., Maejima, Y., Nakata, M., Kodaira, M., Suyama, S., Iwasaki, Y., Kario, K., and Yada, T. (2014). Endogenous GLP-1 acts on paraventricular nucleus to suppress feeding: projection from nucleus tractus solitarius and activation of corticotropin-releasing hormone, nesfatin-1 and oxytocin neurons. Biochem Biophys Res Commun 451, 276–281.Google Scholar
  81. Kelly, J., Alheid, G.F., Newberg, A., and Grossman, S.P. (1977). GABA stimulation and blockade in the hypothalamus and midbrain: effects on feeding and locomotor activity. Pharmacol Biochem Behav 7, 537–541.Google Scholar
  82. Kim, E.R., Leckstrom, A., and Mizuno, T.M. (2008). Impaired anorectic effect of leptin in neurotensin receptor 1-deficient mice. Behav Brain Res 194, 66–71.Google Scholar
  83. Koch, M., Varela, L., Kim, J.G., Kim, J.D., Hernández-Nuño, F., Simonds, S.E., Castorena, C.M., Vianna, C.R., Elmquist, J.K., Morozov, Y.M., et al. (2015). Hypothalamic POMC neurons promote cannabinoid-induced feeding. Nature 519, 45–50.Google Scholar
  84. Kollias, H.D., and McDermott, J.C. (2008). Transforming growth factor-β and myostatin signaling in skeletal muscle. J Appl Physiol 104, 579–587.Google Scholar
  85. Kreisler, A.D., Davis, E.A., and Rinaman, L. (2014). Differential activation of chemically identified neurons in the caudal nucleus of the solitary tract in non-entrained rats after intake of satiating vs. non-satiating meals. Physiol Behav 136, 47–54.Google Scholar
  86. Kristensen, P., Judge, M.E., Thim, L., Ribel, U., Christjansen, K.N., Wulff, B.S., Clausen, J.T., Jensen, P.B., Madsen, O.D., Vrang, N., et al. (1998). Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature 393, 72–76.Google Scholar
  87. Kroemer, N.B., Krebs, L., Kobiella, A., Grimm, O., Pilhatsch, M., Bidlingmaier, M., Zimmermann, U.S., and Smolka, M.N. (2013). Fasting levels of ghrelin covary with the brain response to food pictures. Addict Biol 18, 855–862.Google Scholar
  88. Lam, D.D., Garfield, A.S., Marston, O.J., Shaw, J., and Heisler, L.K. (2010). Brain serotonin system in the coordination of food intake and body weight. Pharmacol Biochem Behav 97, 84–91.Google Scholar
  89. Lane, M.D., Hu, Z., Cha, S.H., Dai, Y., Wolfgang, M., and Sidhaye, A. (2005). Role of malonyl-CoA in the hypothalamic control of food intake and energy expenditure. Biochm Soc Trans 33, 1063–1067.Google Scholar
  90. Langleben, D.D., Busch, E.L., O’Brien, C.P., and Elman, I. (2012). Depot naltrexone decreases rewarding properties of sugar in patients with opioid dependence. Psychopharmacology 220, 559–564.Google Scholar
  91. Lau, J., and Herzog, H. (2014). CART in the regulation of appetite and energy homeostasis. Front Neurosci 8, 313.Google Scholar
  92. Le Foll, C., Dunn-Meynell, A., Musatov, S., Magnan, C., and Levin, B.E. (2013). FAT/CD36: a major regulator of neuronal fatty acid sensing and energy homeostasis in rats and mice. Diabetes 62, 2709–2716.Google Scholar
  93. le Roux, C.W., Batterham, R.L., Aylwin, S.J.B., Patterson, M., Borg, C.M., Wynne, K.J., Kent, A., Vincent, R.P., Gardiner, J., Ghatei, M.A., et al. (2006). Attenuated peptide YY release in obese subjects is associated with reduced satiety. Endocrinology 147, 3–8.Google Scholar
  94. Lechin, F., van der Dijs, B., and Hernández-Adrián, G. (2006). Dorsal raphe vs. median raphe serotonergic antagonism. Anatomical, physiological, behavioral, neuroendocrinological, neuropharmacological and clinical evidences: relevance for neuropharmacological therapy. Prog Neuropsychopharmacol Biol Psychiatry 30, 565–585.Google Scholar
  95. Lee, S.J., Reed, L.A., Davies, M.V., Girgenrath, S., Goad, M.E.P., Tomkinson, K.N., Wright, J.F., Barker, C., Ehrmantraut, G., Holmstrom, J., et al. (2005). Regulation of muscle growth by multiple ligands signaling through activin type II receptors. Proc Natl Acad Sci USA 102, 18117–18122.Google Scholar
  96. Leibowitz, S.F., Chang, G.Q., Dourmashkin, J.T., Yun, R., Julien, C., and Pamy, P.P. (2006). Leptin secretion after a high-fat meal in normal-weight rats: strong predictor of long-term body fat accrual on a high-fat diet. Am J Physiol Endocrinol Metab 290, E258–E267.Google Scholar
  97. Lenglos, C., Mitra, A., Guèvremont, G., and Timofeeva, E. (2013). Sex differences in the effects of chronic stress and food restriction on body weight gain and brain expression of CRF and relaxin-3 in rats. Genes Brain Behav 12, 370–387.Google Scholar
  98. Levey, A.I., Hersch, S.M., Rye, D.B., Sunahara, R.K., Niznik, H.B., Kitt, C. A., Price, D.L., Maggio, R., Brann, M.R., and Ciliax, B.J. (1993). Localization of D1 and D2 dopamine receptors in brain with subtypespecific antibodies. Proc Natl Acad Sci USA 90, 8861–8865.Google Scholar
  99. Lieverse, R.J., Masclee, A.A.M., Jansen, J.B.M.J., Rovati, L.C., and Lamers, C.B.H.W. (1995). Satiety effects of the type A CCK receptor antagonist loxiglumide in lean and obese women. Biol Psychiatry 37, 331–335.Google Scholar
  100. Lin, Z., Tian, H., Lam, K.S.L., Lin, S., Hoo, R.C.L., Konishi, M., Itoh, N., Wang, Y., Bornstein, S.R., Xu, A., et al. (2013). Adiponectin mediates the metabolic effects of FGF21 on glucose homeostasis and insulin sensitivity in mice. Cell Metab 17, 779–789.Google Scholar
  101. Liu, T., Kong, D., Shah, B.P., Ye, C., Koda, S., Saunders, A., Ding, J.B., Yang, Z., Sabatini, B.L., and Lowell, B.B. (2012). Fasting activation of AgRP neurons requires NMDA receptors and involves spinogenesis and increased excitatory tone. Neuron 73, 511–522.Google Scholar
  102. Locke, A.E., Kahali, B., Berndt, S.I., Justice, A.E., Pers, T.H., Day, F.R., Powell, C., Vedantam, S., Buchkovich, M.L., Yang, J., et al. (2015). Genetic studies of body mass index yield new insights for obesity biology. Nature 518, 197–206.Google Scholar
  103. Lockie, S.H., Heppner, K.M., Chaudhary, N., Chabenne, J.R., Morgan, D. A., Veyrat-Durebex, C., Ananthakrishnan, G., Rohner-Jeanrenaud, F., Drucker, D.J., DiMarchi, R., et al. (2012). Direct control of brown adipose tissue thermogenesis by central nervous system glucagon-like peptide-1 receptor signaling. Diabetes 61, 2753–2762.Google Scholar
  104. Maejima, Y., Kohno, D., Iwasaki, Y., and Yada, T. (2011). Insulin suppresses ghrelin-induced calcium signaling in neuropeptide Y neurons of the hypothalamic arcuate nucleus. Aging 3, 1092–1097.Google Scholar
  105. McFadden, K.L., Cornier, M.A., and Tregellas, J.R. (2014). The role of alpha-7 nicotinic receptors in food intake behaviors. Front Psychol 5, 553.Google Scholar
  106. McFarlane, M.R., Brown, M.S., Goldstein, J.L., and Zhao, T.J. (2014). Induced ablation of ghrelin cells in adult mice does not decrease food intake, body weight, or response to high-fat diet. Cell Metab 20, 54–60.Google Scholar
  107. Mebel, D.M., Wong, J.C.Y., Dong, Y.J., and Borgland, S.L. (2012). Insulin in the ventral tegmental area reduces hedonic feeding and suppresses dopamine concentration via increased reuptake. Eur J Neurosci 36, 2336–2346.Google Scholar
  108. Mietlicki-Baase, E.G., Ortinski, P.I., Rupprecht, L.E., Olivos, D.R., Alhadeff, A.L., Pierce, R.C., and Hayes, M.R. (2013). The food intakesuppressive effects of glucagon-like peptide-1 receptor signaling in the ventral tegmental area are mediated by AMPA/kainate receptors. Am J Physiol Endocrinol Metab 305, E1367–E1374.Google Scholar
  109. Mimee, A., and Ferguson, A.V. (2015). Glycemic state regulates melanocortin, but not nesfatin-1, responsiveness of glucose-sensing neurons in the nucleus of the solitary tract. Am J Physiol Regul Integrat Comp Physiol 308, R690–R699.Google Scholar
  110. Mineur, Y.S., Abizaid, A., Rao, Y., Salas, R., DiLeone, R.J., Gündisch, D., Diano, S., De Biasi, M., Horvath, T.L., Gao, X.B., et al. (2011). Nicotine decreases food intake through activation of POMC neurons. Science 332, 1330–1332.Google Scholar
  111. Moran, T.H. (2000). Cholecystokinin and satiety: current perspectives. Nutrition 16, 858–865.Google Scholar
  112. Morris, D.L., and Rui, L. (2009). Recent advances in understanding leptin signaling and leptin resistance. Am J Physiol Endocrinol Metab 297, E1247–E1259.Google Scholar
  113. Morrison, S.F. (2004). Central pathways controlling brown adipose tissue thermogenesis. News Physiol Sci 19, 67–74.Google Scholar
  114. Morton, G.J., Thatcher, B.S., Reidelberger, R.D., Ogimoto, K., Wolden-Hanson, T., Baskin, D.G., Schwartz, M.W., and Blevins, J.E. (2012). Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats. Am J Physiol Endocrinol Metab 302, E134–E144.Google Scholar
  115. Murphy, B.A., Fakira, K.A., Song, Z., Beuve, A., and Routh, V.H. (2009). AMP-activated protein kinase and nitric oxide regulate the glucose sensitivity of ventromedial hypothalamic glucose-inhibited neurons. Am J Physiol Cell Physiol 297, C750–C758.Google Scholar
  116. Murray, E., Brouwer, S., McCutcheon, R., Harmer, C.J., Cowen, P.J., and McCabe, C. (2014). Opposing neural effects of naltrexone on food reward and aversion: implications for the treatment of obesity. Psychopharmacology 231, 4323–4335.Google Scholar
  117. Newgard, C.B., An, J., Bain, J.R., Muehlbauer, M.J., Stevens, R.D., Lien, L.F., Haqq, A.M., Shah, S.H., Arlotto, M., Slentz, C.A., et al. (2009). A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab 9, 311–326.Google Scholar
  118. Nguyen, A.D., Mitchell, N.F., Lin, S., Macia, L., Yulyaningsih, E., Baldock, P.A., Enriquez, R.F., Zhang, L., Shi, Y.C., Zolotukhin, S., et al. (2012). Y1 and Y5 receptors are both required for the regulation of food intake and energy homeostasis in mice. PLoS ONE 7, e40191.Google Scholar
  119. Obici, S., Feng, Z., Morgan, K., Stein, D., Karkanias, G., and Rossetti, L. (2002). Central administration of oleic acid inhibits glucose production and food intake. Diabetes 51, 271–275.Google Scholar
  120. Olszewski, P.K., Cedernaes, J., Olsson, F., Levine, A.S., and Schiöth, H.B. (2008). Analysis of the network of feeding neuroregulators using the Allen Brain Atlas. Neurosci Biobehav Rev 32, 945–956.Google Scholar
  121. Olszewski, P.K., Klockars, A., Olszewska, A.M., Fredriksson, R., Schiöth, H.B., and Levine, A.S. (2010). Molecular, immunohistochemical, and pharmacological evidence of oxytocin’s role as inhibitor of carbohydrate but not fat intake. Endocrinology 151, 4736–4744.Google Scholar
  122. Olszewski, P.K., Klockars, A., Schiöth, H.B., and Levine, A.S. (2010). Oxytocin as feeding inhibitor: maintaining homeostasis in consummatory behavior. Pharmacol Biochem Behav 97, 47–54.Google Scholar
  123. Onaka, T., Takayanagi, Y., and Yoshida, M. (2012). Roles of oxytocin neurones in the control of stress, energy metabolism, and social behaviour. J Neuroendocrinol 24, 587–598.Google Scholar
  124. Ong, Z.Y., Alhadeff, A.L., and Grill, H.J. (2015). Medial nucleus tractus solitarius oxytocin receptor signaling and food intake control: the role of gastrointestinal satiation signal processing. Am J Physiol Regul Integr Comp Physiol 308, R800–R806.Google Scholar
  125. Ott, V., Finlayson, G., Lehnert, H., Heitmann, B., Heinrichs, M., Born, J., and Hallschmid, M. (2013). Oxytocin reduces reward-driven food intake in humans. Diabetes 62, 3418–3425.Google Scholar
  126. Pagotto, U., Marsicano, G., Cota, D., Lutz, B., and Pasquali, R. (2006). The emerging role of the endocannabinoid system in endocrine regulation and energy balance. Endocr Rev 27, 73–100.Google Scholar
  127. Parker, K.L., and Schimmer, B.P. (1997). Steroidogenic factor 1: a key determinant of endocrine development and function. Endocr Rev 18, 361–377.Google Scholar
  128. Patterson, C.M., Leshan, R.L., Jones, J.C., and Myers Jr., M.G. (2011). Molecular mapping of mouse brain regions innervated by leptin receptor-expressing cells. Brain Res 1378, 18–28.Google Scholar
  129. Peciña, S., Cagniard, B., Berridge, K.C., Aldridge, J.W., and Zhuang, X. (2003). Hyperdopaminergic mutant mice have higher “wanting” but not “liking” for sweet rewards. J Neurosci 23, 9395–9402.Google Scholar
  130. Peciña, S., and Smith, K.S. (2010). Hedonic and motivational roles of opioids in food reward: implications for overeating disorders. Pharmacol Biochem Behav 97, 34–46.Google Scholar
  131. Pedersen, B.K., and Febbraio, M.A. (2012). Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol 8, 457–465.Google Scholar
  132. Porte, D., Jr., Baskin, D.G., and Schwartz, M.W. (2005). Insulin signaling in the central nervous system: a critical role in metabolic homeostasis and disease from C. elegans to humans. Diabetes 54, 1264–1276.Google Scholar
  133. Psilopanagioti, A., Papadaki, H., Kranioti, E.F., Alexandrides, T.K., and Varakis, J.N. (2009). Expression of adiponectin and adiponectin receptors in human pituitary gland and brain. Neuroendocrinology 89, 38–47.Google Scholar
  134. Qin, J., Li, Y., Cai, Z., Li, S., Zhu, J., Zhang, F., Liang, S., Zhang, W., Guan, Y., Shen, D., et al. (2012). A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 55–60.Google Scholar
  135. Rabiner, E.A., Beaver, J., Makwana, A., Searle, G., Long, C., Nathan, P.J., Newbould, R.D., Howard, J., Miller, S.R., Bush, M.A., et al. (2011). Molecular and functional neuroimaging of human opioid receptor pharmacology. Mol Psychiatry 16, 785.Google Scholar
  136. Rahmouni, K., Morgan, D.A., Morgan, G.M., Liu, X., Sigmund, C.D., Mark, A.L., and Haynes, W.G. (2004). Hypothalamic PI3K and MAPK differentially mediate regional sympathetic activation to insulin. J Clin Invest 114, 652–658.Google Scholar
  137. Ramnanan, C.J., Saraswathi, V., Smith, M.S., Donahue, E.P., Farmer, B., Farmer, T.D., Neal, D., Williams, P.E., Lautz, M., Mari, A., et al. (2011). Brain insulin action augments hepatic glycogen synthesis without suppressing glucose production or gluconeogenesis in dogs. J Clin Invest 121, 3713–3723.Google Scholar
  138. Re´thelyi, M. (1984). Diffusional barrier around the hypothalamic arcuate nucleus in the rat. Brain Res 307, 355–358.Google Scholar
  139. Richard, J.E., Anderberg, R.H., Göteson, A., Gribble, F.M., Reimann, F., and Skibicka, K.P. (2015). Activation of the GLP-1 receptors in the nucleus of the solitary tract reduces food reward behavior and targets the mesolimbic system. PLoS ONE 10, e0119034.Google Scholar
  140. Richard, J.E., Farkas, I., Anesten, F., Anderberg, R.H., Dickson, S.L., Gribble, F.M., Reimann, F., Jansson, J.O., Liposits, Z., and Skibicka, K. P. (2014). GLP-1 receptor stimulation of the lateral parabrachial nucleus reduces food intake: neuroanatomical, electrophysiological, and behavioral evidence. Endocrinology 155, 4356–4367.Google Scholar
  141. Rinaman, L. (2003). Hindbrain noradrenergic lesions attenuate anorexia and alter central cFos expression in rats after gastric viscerosensory stimulation. J Neurosci 23, 10084–10092.Google Scholar
  142. Roberts, L.D., Boström, P., O’Sullivan, J.F., Schinzel, R.T., Lewis, G.D., Dejam, A., Lee, Y.K., Palma, M.J., Calhoun, S., Georgiadi, A., et al. (2014). β-Aminoisobutyric acid induces browning of white fat and hepatic β-oxidation and is inversely correlated with cardiometabolic risk factors. Cell Metab 19, 96–108.Google Scholar
  143. Rojas-Morales, P., Tapia, E., and Pedraza-Chaverri, J. (2016). beta-Hydroxybutyrate: a signaling metabolite in starvation response? Cell Signal 28, 917–923.Google Scholar
  144. Roman, C.W., Derkach, V.A., and Palmiter, R.D. (2016). Genetically and functionally defined NTS to PBN brain circuits mediating anorexia. Nat Commun 7, 11905.Google Scholar
  145. Routh, V.H., Hao, L., Santiago, A.M., Sheng, Z., and Zhou, C. (2014). Hypothalamic glucose sensing: making ends meet. Front Syst Neurosci 8, 236.Google Scholar
  146. Sahu, A., Carraway, R.E., and Wang, Y.P. (2001). Evidence that neurotensin mediates the central effect of leptin on food intake in rat. Brain Res 888, 343–347.Google Scholar
  147. Samuel, B.S., Shaito, A., Motoike, T., Rey, F.E., Backhed, F., Manchester, J.K., Hammer, R.E., Williams, S.C., Crowley, J., Yanagisawa, M., et al. (2008). Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci USA 105, 16767–16772.Google Scholar
  148. Sato, I., Arima, H., Ozaki, N., Ozaki, N., Watanabe, M., Goto, M., Shimizu, H., Hayashi, M., Banno, R., Nagasaki, H., et al. (2007). Peripherally administered baclofen reduced food intake and body weight in db/db as well as diet-induced obese mice. FEBS Lett 581, 4857–4864.Google Scholar
  149. Savard, P., Mérand, Y., Leblanc, J., and Dupont, A. (1983). Limitation of access to highly palatable foods increases the norepinephrine content of many discrete hypothalamic and amygdaloidal nuclei of rat brain. Life Sci 33, 2513–2519.Google Scholar
  150. Schneeberger, M., Gomis, R., and Claret, M. (2014). Hypothalamic and brainstem neuronal circuits controlling homeostatic energy balance. J Endocrinol 220, T25–T46.Google Scholar
  151. Schultz, W. (2015). Neuronal reward and decision signals: from theories to data. Physiol Rev 95, 853–951.Google Scholar
  152. Schwartz, M.W., Woods, S.C., Porte, D., Seeley, R.J., and Baskin, D.G. (2000). Central nervous system control of food intake. Nature 404, 661–671.Google Scholar
  153. Schwiertz, A., Taras, D., Schäfer, K., Beijer, S., Bos, N.A., Donus, C., and Hardt, P.D. (2010). Microbiota and SCFA in lean and overweight healthy subjects. Obesity 18, 190–195.Google Scholar
  154. Seale, P., Conroe, H.M., Estall, J., Kajimura, S., Frontini, A., Ishibashi, J., Cohen, P., Cinti, S., and Spiegelman, B.M. (2011). Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. J Clin Invest 121, 96–105.Google Scholar
  155. Secher, A., Jelsing, J., Baquero, A.F., Hecksher-Sørensen, J., Cowley, M. A., Dalbøge, L.S., Hansen, G., Grove, K.L., Pyke, C., Raun, K., et al. (2014). The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss. J Clin Invest 124, 4473–4488.Google Scholar
  156. Shanahan, F. (2012). The gut microbiota—a clinical perspective on lessons learned. Nat Rev Gastroenterol Hepatol 9, 609–614.Google Scholar
  157. Sofroniew, M.V. (1983). Morphology of vasopressin and oxytocin neurones and their central and vascular projections. Prog Brain Res 60, 101–114.Google Scholar
  158. Sohn, J.W. (2015). Network of hypothalamic neurons that control appetite. BMB Rep 48, 229–233.Google Scholar
  159. Sola-Penna, M. (2008). Metabolic regulation by lactate. IUBMB Life 60, 605–608.Google Scholar
  160. Srisai, D., Gillum, M.P., Panaro, B.L., Zhang, X.M., Kotchabhakdi, N., Shulman, G.I., Ellacott, K.L.J., and Cone, R.D. (2011). Characterization of the hyperphagic response to dietary fat in the MC4R knockout mouse. Endocrinology 152, 890–902.Google Scholar
  161. Stadler, M., Tomann, L., Storka, A., Wolzt, M., Peric, S., Bieglmayer, C., Pacini, G., Dickson, S.L., Brath, H., Bech, P., et al. (2014). Effects of smoking cessation on β-cell function, insulin sensitivity, body weight, and appetite. Eur J Endocrinol 170, 219–227.Google Scholar
  162. Stolarczyk, E., Guissard, C., Michau, A., Even, P.C., Grosfeld, A., Serradas, P., Lorsignol, A., Pénicaud, L., Brot-Laroche, E., Leturque, A., et al. (2010). Detection of extracellular glucose by GLUT2 contributes to hypothalamic control of food intake. Am J Physiol Endocrinol Metab 298, E1078–E1087.Google Scholar
  163. Sun, J., Gao, Y., Yao, T., Huang, Y., He, Z., Kong, X., Yu, K.J., Wang, R.T., Guo, H., Yan, J., et al. (2016). Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons. Mol Metab 5, 882–891.Google Scholar
  164. Taber, K.H., Black, D.N., Porrino, L.J., and Hurley, R.A. (2012). Neuroanatomy of dopamine: reward and addiction. J Neuropsychiatry Clin Neurosci 24, 1–4.Google Scholar
  165. Taraschenko, O.D., Maisonneuve, I.M., and Glick, S.D. (2011). Resistance of male Sprague-Dawley rats to sucrose-induced obesity: effects of 18-methoxycoronaridine. Physiol Behav 102, 126–131.Google Scholar
  166. Teff, K.L., and Kim, S.F. (2011). Atypical antipsychotics and the neural regulation of food intake and peripheral metabolism. Physiol Behav 104, 590–598.Google Scholar
  167. Tolhurst, G., Heffron, H., Lam, Y.S., Parker, H.E., Habib, A.M., Diakogiannaki, E., Cameron, J., Grosse, J., Reimann, F., and Gribble, F.M. (2012). Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 61, 364–371.Google Scholar
  168. Torii, K., Uneyama, H., and Nakamura, E. (2013). Physiological roles of dietary glutamate signaling via gut-brain axis due to efficient digestion and absorption. J Gastroenterol 48, 442–451.Google Scholar
  169. Torrealba, F., Riveros, M.E., Contreras, M., and Valdes, J.L. (2012). Histamine and motivation. Front Syst Neurosci 6, 51.Google Scholar
  170. Trapp, S., and Cork, S.C. (2015). PPG neurons of the lower brain stem and their role in brain GLP-1 receptor activation. Am J Physiol Regul Integr Comp Physiol 309, R795–R804.Google Scholar
  171. Trivedi, P., Yu, H., MacNeil, D.J., Van der Ploeg, L.H.T., and Guan, X.M. (1998). Distribution of orexin receptor mRNA in the rat brain. FEBS Lett 438, 71–75.Google Scholar
  172. Unger, T.J., Calderon, G.A., Bradley, L.C., Sena-Esteves, M., and Rios, M. (2007). Selective deletion of Bdnf in the ventromedial and dorsomedial hypothalamus of adult mice results in hyperphagic behavior and obesity. J Neurosci 27, 14265–14274.Google Scholar
  173. Vaccari, C., Lolait, S.J., and Ostrowski, N.L. (1998). Comparative distribution of vasopressin V1b and oxytocin receptor messenger ribonucleic acids in brain. Endocrinology 139, 5015–5033.Google Scholar
  174. Valdés, J.L., Sánchez, C., Riveros, M.E., Blandina, P., Contreras, M., Farías, P., and Torrealba, F. (2010). The histaminergic tuberomammillary nucleus is critical for motivated arousal. Eur J Neurosci 31, 2073–2085.Google Scholar
  175. van de Giessen, E., Celik, F., Schweitzer, D.H., van den Brink, W., and Booij, J. (2014). Dopamine D2/3 receptor availability and amphetamineinduced dopamine release in obesity. J Psychopharmacol 28, 866–873.Google Scholar
  176. van Marken Lichtenbelt, W.D., Vanhommerig, J.W., Smulders, N.M., Drossaerts, J.M.A.F.L., Kemerink, G.J., Bouvy, N.D., Schrauwen, P., and Teule, G.J.J. (2009). Cold-activated brown adipose tissue in healthy men. N Engl J Med 360, 1500–1508.Google Scholar
  177. van Zessen, R., Phillips, J.L., Budygin, E.A., and Stuber, G.D. (2012). Activation of VTA GABA neurons disrupts reward consumption. Neuron 73, 1184–1194.Google Scholar
  178. Ventura, R., Morrone, C., and Puglisi-Allegra, S. (2007). Prefrontal/accumbal catecholamine system determines motivational salience attribution to both reward- and aversion-related stimuli. Proc Natl Acad Sci USA 104, 5181–5186.Google Scholar
  179. Villanueva, E.C., and Myers, M.G. (2008). Leptin receptor signaling and the regulation of mammalian physiology. Int J Obes 32, S8–S12.Google Scholar
  180. Voigt, J.P., and Fink, H. (2015). Serotonin controlling feeding and satiety. Behav Brain Res 277, 14–31.Google Scholar
  181. Volkow, N.D., Wang, G.J., Telang, F., Fowler, J.S., Thanos, P.K., Logan, J., Alexoff, D., Ding, Y.S., Wong, C., Ma, Y., et al. (2008). Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors. Neuroimage 42, 1537–1543.Google Scholar
  182. Wang, C.F., Billington, C.J., Levine, A.S., and Kotz, C.M. (2000). Effect of CART in the hypothalamic paraventricular nucleus on feeding and uncoupling protein gene expression. Neuroreport 11, 3251–3255.Google Scholar
  183. Wang, G.J., Volkow, N.D., Logan, J., Pappas, N.R., Wong, C.T., Zhu, W., Netusll, N., and Fowler, J.S. (2001). Brain dopamine and obesity. Lancet 357, 354–357.Google Scholar
  184. Wellman, P.J. (2000). Norepinephrine and the control of food intake. Nutrition 16, 837–842.Google Scholar
  185. West, D.B., Fey D., and Woods, S.C. (1984). Cholecystokinin persistently suppresses meal size but not food intake in free-feeding rats. Am J Physiol 246, R776–787.Google Scholar
  186. Williams, D.L. (2014). Neural integration of satiation and food reward: role of GLP-1 and orexin pathways. Physiol Behav 136, 194–199.Google Scholar
  187. Wise, R.A., and Bozarth, M.A. (1987). A psychomotor stimulant theory of addiction. Psychol Rev 94, 469–492.Google Scholar
  188. Xu, A., Wang, Y., Keshaw, H., Xu, L.Y., Lam, K.S.L., and Cooper, G.J.S. (2003). The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J Clin Invest 112, 91–100.Google Scholar
  189. Yamada, H., Okumura, T., Motomura, W., Kobayashi, Y., and Kohgo, Y. (2000). Inhibition of food intake by central injection of anti-orexin antibody in fasted rats. Biochem Biophys Res Commun 267, 527–531.Google Scholar
  190. Yamada, M., Miyakawa, T., Duttaroy, A., Yamanaka, A., Moriguchi, T., Makita, R., Ogawa, M., Chou, C.J., Xia, B., Crawley, J.N., et al. (2001). Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean. Nature 410, 207–212.Google Scholar
  191. Yamauchi, T., Iwabu, M., Okada-Iwabu, M., and Kadowaki, T. (2014). Adiponectin receptors: a review of their structure, function and how they work. Best Practice Res Clin Endocrinol Metab 28, 15–23.Google Scholar
  192. Yamauchi, T., Kamon, J., Minokoshi, Y., Ito, Y., Waki, H., Uchida, S., Yamashita, S., Noda, M., Kita, S., Ueki, K., et al. (2002). Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8, 1288–1295.Google Scholar
  193. Yamauchi, T., Kamon, J., Waki, H., Imai, Y., Shimozawa, N., Hioki, K., Uchida, S., Ito, Y., Takakuwa, K., Matsui, J., et al. (2003). Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J Biol Chem 278, 2461–2468.Google Scholar
  194. Yamauchi, T., Nio, Y., Maki, T., Kobayashi, M., Takazawa, T., Iwabu, M., Okada-Iwabu, M., Kawamoto, S., Kubota, N., Kubota, T., et al. (2007). Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med 13, 332–339.Google Scholar
  195. Yang, J., Brown, M.S., Liang, G., Grishin, N.V., and Goldstein, J.L. (2008). Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell 132, 387–396.Google Scholar
  196. Yeo, G.S.H., Connie Hung, C.C., Rochford, J., Keogh, J., Gray, J., Sivaramakrishnan, S., O’Rahilly, S., and Farooqi, I.S. (2004). A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nat Neurosci 7, 1187–1189.Google Scholar
  197. Yeomans, M.R., and Gray, R.W. (1996). Selective effects of naltrexone on food pleasantness and intake. Physiol Behav 60, 439–446.Google Scholar
  198. Yoshida, K., Li, X., Cano, G., Lazarus, M., and Saper, C.B. (2009). Parallel preoptic pathways for thermoregulation. J Neurosci 29, 11954–11964.Google Scholar
  199. Zheng, H., and Berthoud, H.R. (2008). Neural systems controlling the drive to eat: mind versus metabolism. Physiology (Bethesda) 23, 75–83.Google Scholar
  200. Zhou, L., Podolsky, N., Sang, Z., Ding, Y., Fan, X., Tong, Q., Levin, B.E., and McCrimmon, R.J. (2010). The medial amygdalar nucleus: a novel glucose-sensing region that modulates the counterregulatory response to hypoglycemia. Diabetes 59, 2646–2652.Google Scholar
  201. Zhou, L., Sutton, G.M., Rochford, J.J., Semple, R.K., Lam, D.D., Oksanen, L.J., Thornton-Jones, Z.D., Clifton, P.G., Yueh, C.Y., Evans, M.L., et al. (2007). Serotonin 2C receptor agonists improve type 2 diabetes via melanocortin-4 receptor signaling pathways. Cell Metab 6, 398–405.Google Scholar

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© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Endocrinology, Shanghai Pudong HospitalFudan UniversityShanghaiChina

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