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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adams, S.H. (2011). Emerging perspectives on essential amino acid metabolism in obesity and the insulin-resistant state. Adv Nutr 2, 445–456.
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.
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.
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.
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.
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.
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.
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.
Audrain-McGovern, J., and Benowitz, N.L. (2011). Cigarette smoking, nicotine, and body weight. Clin Pharmacol Ther 90, 164–168.
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.
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.
Baik, J.H. (2013). Dopamine signaling in food addiction: role of dopamine D2 receptors. BMB Rep 46, 519–526.
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.
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.
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.
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.
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.
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.
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.
Björklund, A., and Dunnett, S.B. (2007). Dopamine neuron systems in the brain: an update. Trends Neurosci 30, 194–202.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Chronwall, B.M. (1985). Anatomy and physiology of the neuroendocrine arcuate nucleus. Peptides 6 Suppl 2, 1–11.
Cone, R.D. (2005). Anatomy and regulation of the central melanocortin system. Nat Neurosci 8, 571–578.
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.
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.
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.
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.
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.
Cryer, P.E., Davis, S.N., and Shamoon, H. (2003). Hypoglycemia in diabetes. Diabetes Care 26, 1902–1912.
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.
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.
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.
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.
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.
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.
Drucker, D.J. (2006). The biology of incretin hormones. Cell Metab 3, 153–165.
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.
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.
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.
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.
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.
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.
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.
Garfield, A.S., and Heisler, L.K. (2009). Pharmacological targeting of the serotonergic system for the treatment of obesity. J Physiol 587, 49–60.
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.
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.
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.
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.
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.
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.
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.
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.
Hayes, D.J., and Greenshaw, A.J. (2011). 5-HT receptors and rewardrelated behaviour: a review. Neurosci Biobehav Rev 35, 1419–1449.
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.
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.
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.
Hensler, J.G. (2006). Serotonergic modulation of the limbic system. Neurosci Biobehav Rev 30, 203–214.
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.
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.
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.
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.
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.
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.
Ikemoto, S. (2010). Brain reward circuitry beyond the mesolimbic dopamine system: a neurobiological theory. Neurosci BioBehav Rev 35, 129–150.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Kollias, H.D., and McDermott, J.C. (2008). Transforming growth factor-β and myostatin signaling in skeletal muscle. J Appl Physiol 104, 579–587.
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.
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.
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.
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.
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.
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.
Lau, J., and Herzog, H. (2014). CART in the regulation of appetite and energy homeostasis. Front Neurosci 8, 313.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Moran, T.H. (2000). Cholecystokinin and satiety: current perspectives. Nutrition 16, 858–865.
Morris, D.L., and Rui, L. (2009). Recent advances in understanding leptin signaling and leptin resistance. Am J Physiol Endocrinol Metab 297, E1247–E1259.
Morrison, S.F. (2004). Central pathways controlling brown adipose tissue thermogenesis. News Physiol Sci 19, 67–74.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Parker, K.L., and Schimmer, B.P. (1997). Steroidogenic factor 1: a key determinant of endocrine development and function. Endocr Rev 18, 361–377.
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.
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.
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.
Pedersen, B.K., and Febbraio, M.A. (2012). Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol 8, 457–465.
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.
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.
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.
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.
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.
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.
Re´thelyi, M. (1984). Diffusional barrier around the hypothalamic arcuate nucleus in the rat. Brain Res 307, 355–358.
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.
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.
Rinaman, L. (2003). Hindbrain noradrenergic lesions attenuate anorexia and alter central cFos expression in rats after gastric viscerosensory stimulation. J Neurosci 23, 10084–10092.
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.
Rojas-Morales, P., Tapia, E., and Pedraza-Chaverri, J. (2016). beta-Hydroxybutyrate: a signaling metabolite in starvation response? Cell Signal 28, 917–923.
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.
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.
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.
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.
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.
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.
Schneeberger, M., Gomis, R., and Claret, M. (2014). Hypothalamic and brainstem neuronal circuits controlling homeostatic energy balance. J Endocrinol 220, T25–T46.
Schultz, W. (2015). Neuronal reward and decision signals: from theories to data. Physiol Rev 95, 853–951.
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.
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.
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.
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.
Shanahan, F. (2012). The gut microbiota—a clinical perspective on lessons learned. Nat Rev Gastroenterol Hepatol 9, 609–614.
Sofroniew, M.V. (1983). Morphology of vasopressin and oxytocin neurones and their central and vascular projections. Prog Brain Res 60, 101–114.
Sohn, J.W. (2015). Network of hypothalamic neurons that control appetite. BMB Rep 48, 229–233.
Sola-Penna, M. (2008). Metabolic regulation by lactate. IUBMB Life 60, 605–608.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Torrealba, F., Riveros, M.E., Contreras, M., and Valdes, J.L. (2012). Histamine and motivation. Front Syst Neurosci 6, 51.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Villanueva, E.C., and Myers, M.G. (2008). Leptin receptor signaling and the regulation of mammalian physiology. Int J Obes 32, S8–S12.
Voigt, J.P., and Fink, H. (2015). Serotonin controlling feeding and satiety. Behav Brain Res 277, 14–31.
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.
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.
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.
Wellman, P.J. (2000). Norepinephrine and the control of food intake. Nutrition 16, 837–842.
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.
Williams, D.L. (2014). Neural integration of satiation and food reward: role of GLP-1 and orexin pathways. Physiol Behav 136, 194–199.
Wise, R.A., and Bozarth, M.A. (1987). A psychomotor stimulant theory of addiction. Psychol Rev 94, 469–492.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Yeomans, M.R., and Gray, R.W. (1996). Selective effects of naltrexone on food pleasantness and intake. Physiol Behav 60, 439–446.
Yoshida, K., Li, X., Cano, G., Lazarus, M., and Saper, C.B. (2009). Parallel preoptic pathways for thermoregulation. J Neurosci 29, 11954–11964.
Zheng, H., and Berthoud, H.R. (2008). Neural systems controlling the drive to eat: mind versus metabolism. Physiology (Bethesda) 23, 75–83.
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.
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.
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).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wen, S., Wang, C., Gong, M. et al. An overview of energy and metabolic regulation. Sci. China Life Sci. 62, 771–790 (2019). https://doi.org/10.1007/s11427-018-9371-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-018-9371-4