Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

The neuroscience of sugars in taste, gut-reward, feeding circuits, and obesity


Throughout the animal kingdom sucrose is one of the most palatable and preferred tastants. From an evolutionary perspective, this is not surprising as it is a primary source of energy. However, its overconsumption can result in obesity and an associated cornucopia of maladies, including type 2 diabetes and cardiovascular disease. Here we describe three physiological levels of processing sucrose that are involved in the decision to ingest it: the tongue, gut, and brain. The first section describes the peripheral cellular and molecular mechanisms of sweet taste identification that project to higher brain centers. We argue that stimulation of the tongue with sucrose triggers the formation of three distinct pathways that convey sensory attributes about its quality, palatability, and intensity that results in a perception of sweet taste. We also discuss the coding of sucrose throughout the gustatory pathway. The second section reviews how sucrose, and other palatable foods, interact with the gut–brain axis either through the hepatoportal system and/or vagal pathways in a manner that encodes both the rewarding and of nutritional value of foods. The third section reviews the homeostatic, hedonic, and aversive brain circuits involved in the control of food intake. Finally, we discuss evidence that overconsumption of sugars (or high fat diets) blunts taste perception, the post-ingestive nutritional reward value, and the circuits that control feeding in a manner that can lead to the development of obesity.

This is a preview of subscription content, log in to check access.

Fig. 1

Adapted from [270]

Fig. 2

Figure with permission from [39]

Fig. 3
Fig. 4

Reprinted with permission from [8] and [71]

Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

From [217]



5-Hydroxytryptamine or serotonin


Agouti-related protein


Anterior insular cortex


Arcuate nucleus of the hypothalamus


Amino-terminal domain


Basolateral amygdala


Bed nucleus of the stria terminalis


Ca2+-activated and voltage-dependent Ca2+ homeostasis modulator 1/3 hetero-hexameric ion channel




Cadherin 4


Central amygdala




Cranial nerve


Central nervous system


Cystein-rich domain


Chorda tympani






Dopamine transporter promotor


Dorsal striatum


Enteroendocrine cells


Early growth response 2


Epithelial Na+ channel


Geniculate ganglion


Glucose-dependent insulinotropic peptide


Glucagon-like peptide-1


Sensory branch of the glossopharyngeal nerve


Insular cortex



IP3 :

Inositol triphosphate


Inositol 1,4,5-trisphosphate receptor type 3


Inferior petrosal ganglion


Glucose transporter 4


G-protein coupled receptor


Sensory branch of the glossopharyngeal nerve


Great superficial petrosal nerve


High fat diet


Ninth glossopharyngeal cranial nerve


Lateral nucleus accumbens


Lateral ventral tegmental area


Lateral hypothalamic area

LHAVgat+ :

Lateral hypothalamic area neuron expressing vesicular GABA transporter

LHAVglut2+ :

Lateral hypothalamic area neuron expressing vesicular glutamatergic transporter 2


Melanin-concentrating hormone


Medium spiny neuron

MSND1+ :

Medium spiny neuron expressing dopamine D1 receptor

MSND2+ :

Medium spiny neuron expressing dopamine D2 receptor


Nucleus accumbens shell


Nodose ganglion


Nucleus tractus solitarius




Orbitofrontal cortex






Parabrachial nucleus


Prodynorphin gene


Proenkephalin gene


Posterior insular cortex

PIP2 :

Phosphatidylinositol 4,5-bisphosphate


Proopiomelanocortin protein


Peroxisome proliferator-associated receptor-α


Paraventricular hypothalamus


Paraventricular thalamus


Peptide YY


Receptors activated solely by synthetic ligands


Rostral portion of the nucleus tractus solitarius


Sodium-glucose linked transporter 1


Superior laryngeal branch


Substantia nigra pars compacta


Spondin-1 gene


Sugar-sweetened beverages


Taste 1 receptor member 3 gene


Transmembrane domain


Taste receptor cell


Transient receptor potential cation channel subfamily M member 4


Transient receptor potential cation channel subfamily M member 5


Venus flytrap domain


Ventral hippocampus


Seventh facial cranial nerve


Ventromedial nucleus accumbens


Ventromedial ventral tegmental area


Parvocellular portion of the ventroposteromedial thalamus


Ventral striatum


Ventral tegmental area


GABAergic interneurons in the ventral tegmental area


CN10th vagus nerve


Zona incerta


  1. 1.

    Breslin PAS (2013) An evolutionary perspective on food and human taste. Curr Biol 23:R409–R418. https://doi.org/10.1016/j.cub.2013.04.010

  2. 2.

    Gutierrez R, Simon SA (2015) Why do people living in hot climates like their food spicy? Temp Multidiscip Biomed J 3:48–49. https://doi.org/10.1080/23328940.2015.1119616

  3. 3.

    Simon SA, de Araujo IE, Gutierrez R, Nicolelis MAL (2006) The neural mechanisms of gustation: a distributed processing code. Nat Rev Neurosci 7:890. https://doi.org/10.1038/nrn2006

  4. 4.

    Glendinning JI, Stano S, Holter M et al (2015) Sugar-induced cephalic-phase insulin release is mediated by a T1r2 + T1r3-independent taste transduction pathway in mice. Am J Physiol Regul Integr Comp Physiol 309:R552–R560. https://doi.org/10.1152/ajpregu.00056.2015

  5. 5.

    Belloir C, Neiers F, Briand L (2017) Sweeteners and sweetness enhancers. Curr Opin Clin Nutr Metab Care 20:279–285. https://doi.org/10.1097/MCO.0000000000000377

  6. 6.

    McGee H (2004) On food and cooking: the science and lore of the kitchen. Scribner, New York

  7. 7.

    Lapis TJ, Penner MH, Lim J (2014) Evidence that humans can taste glucose polymers. Chem Senses 39:737–747. https://doi.org/10.1093/chemse/bju031

  8. 8.

    Yarmolinsky DA, Zuker CS, Ryba NJP (2009) Common sense about taste: from mammals to insects. Cell 139:234–244. https://doi.org/10.1016/j.cell.2009.10.001

  9. 9.

    David Dickman J, Smith DV (1988) Response properties of fibers in the hamster superior laryngeal nerve. Brain Res 450:25–38. https://doi.org/10.1016/0006-8993(88)91541-7

  10. 10.

    Ohkuri T, Horio N, Stratford JM et al (2012) Residual chemoresponsiveness to acids in the superior laryngeal nerve in “taste-blind” (P2X2/P2X3 double-KO) mice. Chem Senses 37:523–532. https://doi.org/10.1093/chemse/bjs004

  11. 11.

    Smith DV, Hanamori T (1991) Organization of gustatory sensitivities in hamster superior laryngeal nerve fibers. J Neurophysiol 65:1098–1114. https://doi.org/10.1152/jn.1991.65.5.1098

  12. 12.

    Mouillot T, Szleper E, Vagne G et al (2019) Cerebral gustatory activation in response to free fatty acids using gustatory evoked potentials in humans. J Lipid Res 60:661–670. https://doi.org/10.1194/jlr.M086587

  13. 13.

    Vandenbeuch A, Clapp TR, Kinnamon SC (2008) Amiloride-sensitive channels in type I fungiform taste cells in mouse. BMC Neurosci 9:1. https://doi.org/10.1186/1471-2202-9-1

  14. 14.

    Roper SD (2015) The taste of table salt. Pflugers Arch 467:457–463. https://doi.org/10.1007/s00424-014-1683-z

  15. 15.

    Roper SD, Chaudhari N (2017) Taste buds: cells, signals and synapses. Nat Rev Neurosci 18:485–497. https://doi.org/10.1038/nrn.2017.68

  16. 16.

    Oka Y, Butnaru M, von Buchholtz L et al (2013) High salt recruits aversive taste pathways. Nature 494:472–475. https://doi.org/10.1038/nature11905

  17. 17.

    Yasumatsu K, Ogiwara Y, Takai S et al (2012) Umami taste in mice uses multiple receptors and transduction pathways. J Physiol 590:1155–1170. https://doi.org/10.1113/jphysiol.2011.211920

  18. 18.

    Heck GL, Mierson S, DeSimone JA (1984) Salt taste transduction occurs through an amiloride-sensitive sodium transport pathway. Science 223:403–405. https://doi.org/10.1126/science.6691151

  19. 19.

    Chandrashekar J, Kuhn C, Oka Y et al (2010) The cells and peripheral representation of sodium taste in mice. Nature 464:297–301. https://doi.org/10.1038/nature08783

  20. 20.

    Bigiani A, Cuoghi V (2007) Localization of amiloride-sensitive sodium current and voltage-gated calcium currents in rat fungiform taste cells. J Neurophysiol 98:2483–2487. https://doi.org/10.1152/jn.00716.2007

  21. 21.

    Lewandowski BC, Sukumaran SK, Margolskee RF, Bachmanov AA (2016) Amiloride-insensitive salt taste is mediated by two populations of type III taste cells with distinct transduction mechanisms. J Neurosci Off J Soc Neurosci 36:1942–1953. https://doi.org/10.1523/JNEUROSCI.2947-15.2016

  22. 22.

    Roebber JK, Roper SD, Chaudhari N (2019) the role of the anion in salt (NaCl) detection by mouse taste buds. J Neurosci 39:6224–6232. https://doi.org/10.1523/JNEUROSCI.2367-18.2019

  23. 23.

    Ramsey IS, DeSimone JA (2018) Otopetrin-1: a sour-tasting proton channel. J Gen Physiol 150:379–382. https://doi.org/10.1085/jgp.201812003

  24. 24.

    Tu Y-H, Cooper AJ, Teng B et al (2018) An evolutionarily conserved gene family encodes proton-selective ion channels. Science 359:1047–1050. https://doi.org/10.1126/science.aao3264

  25. 25.

    Zhang J, Jin H, Zhang W et al (2019) Sour sensing from the tongue to the brain. Cell. https://doi.org/10.1016/j.cell.2019.08.031

  26. 26.

    Teng B, Wilson CE, Tu Y-H et al (2019) Cellular and neural responses to sour stimuli require the proton channel Otop1. Curr Biol. https://doi.org/10.1016/j.cub.2019.08.077

  27. 27.

    Ye W, Chang RB, Bushman JD et al (2016) The K + channel KIR2.1 functions in tandem with proton influx to mediate sour taste transduction. Proc Natl Acad Sci 113:E229–E238. https://doi.org/10.1073/pnas.1514282112

  28. 28.

    Wilson CE, Vandenbeuch A, Kinnamon SC (2019) Physiological and behavioral responses to optogenetic stimulation of PKD2L1 + type III taste cells. eNeuro 6. https://doi.org/10.1523/ENEURO.0107-19.2019

  29. 29.

    Zocchi D, Wennemuth G, Oka Y (2017) The cellular mechanism for water detection in the mammalian taste system. Nat Neurosci 20:927–933. https://doi.org/10.1038/nn.4575

  30. 30.

    Chandrashekar J, Yarmolinsky D, von Buchholtz L et al (2009) The taste of carbonation. Science 326:443–445. https://doi.org/10.1126/science.1174601

  31. 31.

    Yang R, Dzowo YK, Wilson CE, et al (2019) Three-dimensional reconstructions of mouse circumvallate taste buds using serial blockface scanning electron microscopy: I. cell types and the apical region of the taste bud. bioRxiv 610410. https://doi.org/10.1101/610410

  32. 32.

    Pérez CA, Huang L, Rong M et al (2002) A transient receptor potential channel expressed in taste receptor cells. Nat Neurosci 5:1169. https://doi.org/10.1038/nn952

  33. 33.

    Dutta Banik D, Martin LE, Freichel M et al (2018) TRPM4 and TRPM5 are both required for normal signaling in taste receptor cells. Proc Natl Acad Sci U S A 115:E772–E781. https://doi.org/10.1073/pnas.1718802115

  34. 34.

    Taruno A, Vingtdeux V, Ohmoto M et al (2013) CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes. Nature 495:223–226. https://doi.org/10.1038/nature11906

  35. 35.

    Ma Z, Taruno A, Ohmoto M et al (2018) CALHM3 is essential for rapid ion channel-mediated purinergic neurotransmission of GPCR-mediated tastes. Neuron 98:547–561.e10. https://doi.org/10.1016/j.neuron.2018.03.043

  36. 36.

    Finger TE, Danilova V, Barrows J et al (2005) ATP signaling is crucial for communication from taste buds to gustatory nerves. Science 310:1495–1499. https://doi.org/10.1126/science.1118435

  37. 37.

    Nelson G, Chandrashekar J, Hoon MA et al (2002) An amino-acid taste receptor. Nature 416:199–202. https://doi.org/10.1038/nature726

  38. 38.

    Nelson G, Hoon MA, Chandrashekar J et al (2001) Mammalian sweet taste receptors. Cell 106:381–390. https://doi.org/10.1016/s0092-8674(01)00451-2

  39. 39.

    Laffitte A, Neiers F, Briand L (2014) Functional roles of the sweet taste receptor in oral and extraoral tissues. Curr Opin Clin Nutr Metab Care 17:379–385. https://doi.org/10.1097/MCO.0000000000000058

  40. 40.

    Zhao GQ, Zhang Y, Hoon MA et al (2003) The receptors for mammalian sweet and umami taste. Cell 115:255–266. https://doi.org/10.1016/s0092-8674(03)00844-4

  41. 41.

    Nie Y, Vigues S, Hobbs JR et al (2005) Distinct contributions of T1R2 and T1R3 taste receptor subunits to the detection of sweet stimuli. Curr Biol CB 15:1948–1952. https://doi.org/10.1016/j.cub.2005.09.037

  42. 42.

    Masuda T, Taguchi W, Sano A et al (2013) Five amino acid residues in cysteine-rich domain of human T1R3 were involved in the response for sweet-tasting protein, thaumatin. Biochimie 95:1502–1505. https://doi.org/10.1016/j.biochi.2013.01.010

  43. 43.

    DuBois GE (2016) Molecular mechanism of sweetness sensation. Physiol Behav 164:453–463. https://doi.org/10.1016/j.physbeh.2016.03.015

  44. 44.

    Cui M, Jiang P, Maillet E et al (2006) The heterodimeric sweet taste receptor has multiple potential ligand binding sites. Curr Pharm Des 12:4591–4600

  45. 45.

    Han J, Choi M (2018) Comprehensive functional screening of taste sensation in vivo. bioRxiv 371682. https://doi.org/10.1101/371682

  46. 46.

    Behrens M, Meyerhof W (2011) Gustatory and extragustatory functions of mammalian taste receptors. Physiol Behav 105:4–13. https://doi.org/10.1016/j.physbeh.2011.02.010

  47. 47.

    Reed DR, Li S, Li X et al (2004) Polymorphisms in the taste receptor gene (Tas1r3) Region are associated with saccharin preference in 30 mouse strains. J Neurosci 24:938–946. https://doi.org/10.1523/JNEUROSCI.1374-03.2004

  48. 48.

    Loney GC, Blonde GD, Eckel LA, Spector AC (2012) Determinants of taste preference and acceptability: quality versus hedonics. J Neurosci 32:10086–10092. https://doi.org/10.1523/JNEUROSCI.6036-11.2012

  49. 49.

    Li X, Li W, Wang H et al (2006) Cats lack a sweet taste receptor. J Nutr 136:1932S–1934S

  50. 50.

    Baldwin MW, Toda Y, Nakagita T et al (2014) Evolution of sweet taste perception in hummingbirds by transformation of the ancestral umami receptor. Science 345:929–933. https://doi.org/10.1126/science.1255097

  51. 51.

    Schiffman SS, Booth BJ, Losee ML et al (1995) Bitterness of sweeteners as a function of concentration. Brain Res Bull 36:505–513. https://doi.org/10.1016/0361-9230(94)00225-P

  52. 52.

    Servant G, Tachdjian C, Li X, Karanewsky DS (2011) The sweet taste of true synergy: positive allosteric modulation of the human sweet taste receptor. Trends Pharmacol Sci 32:631–636. https://doi.org/10.1016/j.tips.2011.06.007

  53. 53.

    Ninomiya Y, Imoto T (1995) Gurmarin inhibition of sweet taste responses in mice. Am J Physiol-Regul Integr Comp Physiol 268:R1019–R1025. https://doi.org/10.1152/ajpregu.1995.268.4.R1019

  54. 54.

    Sanematsu K, Shigemura N, Ninomiya Y (2017) Binding properties between human sweet receptor and sweet-inhibitor, gymnemic acids. J Oral Biosci 59:127–130. https://doi.org/10.1016/j.job.2017.05.004

  55. 55.

    Sigoillot M, Brockhoff A, Meyerhof W, Briand L (2012) Sweet-taste-suppressing compounds: current knowledge and perspectives of application. Appl Microbiol Biotechnol 96:619–630. https://doi.org/10.1007/s00253-012-4387-3

  56. 56.

    O’Connell S (2012) Sugar: the grass that changed the world. Virgin, London

  57. 57.

    Damak S, Rong M, Yasumatsu K et al (2003) Detection of sweet and umami taste in the absence of taste receptor T1r3. Science 301:850–853. https://doi.org/10.1126/science.1087155

  58. 58.

    Merigo F, Benati D, Cristofoletti M et al (2011) Glucose transporters are expressed in taste receptor cells. J Anat 219:243–252. https://doi.org/10.1111/j.1469-7580.2011.01385.x

  59. 59.

    Yee KK, Sukumaran SK, Kotha R et al (2011) Glucose transporters and ATP-gated K + (KATP) metabolic sensors are present in type 1 taste receptor 3 (T1r3)-expressing taste cells. Proc Natl Acad Sci USA 108:5431–5436. https://doi.org/10.1073/pnas.1100495108

  60. 60.

    Sukumaran SK, Yee KK, Iwata S et al (2016) Taste cell-expressed α-glucosidase enzymes contribute to gustatory responses to disaccharides. Proc Natl Acad Sci 113:6035–6040. https://doi.org/10.1073/pnas.1520843113

  61. 61.

    Delaere F, Duchampt A, Mounien L et al (2012) The role of sodium-coupled glucose co-transporter 3 in the satiety effect of portal glucose sensing. Mol Metab 2:47–53. https://doi.org/10.1016/j.molmet.2012.11.003

  62. 62.

    Sclafani A, Koepsell H, Ackroff K (2016) SGLT1 sugar transporter/sensor is required for post-oral glucose appetition. Am J Physiol-Regul Integr Comp Physiol 310:R631–R639. https://doi.org/10.1152/ajpregu.00432.2015

  63. 63.

    de Araujo IE, Oliveira-Maia AJ, Sotnikova TD et al (2008) Food reward in the absence of taste receptor signaling. Neuron 57:930–941. https://doi.org/10.1016/j.neuron.2008.01.032

  64. 64.

    Mueller KL, Hoon MA, Erlenbach I et al (2005) The receptors and coding logic for bitter taste. Nature 434:225–229. https://doi.org/10.1038/nature03352

  65. 65.

    Marella S, Fischler W, Kong P et al (2006) Imaging taste responses in the fly brain reveals a functional map of taste category and behavior. Neuron 49:285–295. https://doi.org/10.1016/j.neuron.2005.11.037

  66. 66.

    Ohla K, Yoshida R, Roper SD et al (2019) Recognizing taste: coding patterns along the neural axis in mammals. Chem Senses 44:237–247. https://doi.org/10.1093/chemse/bjz013

  67. 67.

    Villavicencio M, Moreno MG, Simon SA, Gutierrez R (2018) Encoding of sucrose’s palatability in the nucleus accumbens shell and its modulation by exteroceptive auditory cues. Front Neurosci 12:265. https://doi.org/10.3389/fnins.2018.00265

  68. 68.

    Frank ME, Contreras RJ, Hettinger TP (1983) Nerve fibers sensitive to ionic taste stimuli in chorda tympani of the rat. J Neurophysiol 50:941–960. https://doi.org/10.1152/jn.1983.50.4.941

  69. 69.

    Tokita K, Boughter JD (2016) Topographic organizations of taste-responsive neurons in the parabrachial nucleus of C57BL/6J mice: an electrophysiological mapping study. Neuroscience 316:151–166. https://doi.org/10.1016/j.neuroscience.2015.12.030

  70. 70.

    Yamamoto T, Matsuo R, Kiyomitsu Y, Kitamura R (1989) Taste responses of cortical neurons in freely ingesting rats. J Neurophysiol 61:1244–1258. https://doi.org/10.1152/jn.1989.61.6.1244

  71. 71.

    Barretto RPJ, Gillis-Smith S, Chandrashekar J et al (2015) The neural representation of taste quality at the periphery. Nature 517:373–376. https://doi.org/10.1038/nature13873

  72. 72.

    Erickson RP (2001) The evolution and implications of population and modular neural coding ideas. Prog Brain Res 130:9–29

  73. 73.

    Erickson RP (2008) A study of the science of taste: on the origins and influence of the core ideas. Behav Brain Sci 31:59–75. https://doi.org/10.1017/S0140525X08003348(discussion 75–105)

  74. 74.

    Wu A, Dvoryanchikov G, Pereira E et al (2015) Breadth of tuning in taste afferent neurons varies with stimulus strength. Nat Commun 6:8171. https://doi.org/10.1038/ncomms9171

  75. 75.

    Tomchik SM, Berg S, Kim JW et al (2007) Breadth of tuning and taste coding in mammalian taste buds. J Neurosci 27:10840–10848. https://doi.org/10.1523/JNEUROSCI.1863-07.2007

  76. 76.

    Ootani S, Umezaki T, Shin T, Murata Y (1995) Convergence of afferents from the SLN and GPN in cat medullary swallowing neurons. Brain Res Bull 37:397–404. https://doi.org/10.1016/0361-9230(95)00018-6

  77. 77.

    Spector AC (2000) Linking gustatory neurobiology to behavior in vertebrates. Neurosci Biobehav Rev 24:391–416. https://doi.org/10.1016/S0149-7634(00)00013-0

  78. 78.

    Danilova V, Danilov Y, Roberts T et al (2002) Sense of taste in a new world monkey, the common marmoset: recordings from the chorda tympani and glossopharyngeal nerves. J Neurophysiol 88:579–594. https://doi.org/10.1152/jn.2002.88.2.579

  79. 79.

    Pfaffmann C (1941) Gustatory afferent impulses. J Cell Comp Physiol 17:243–258. https://doi.org/10.1002/jcp.1030170209

  80. 80.

    Breza JM, Nikonov AA, Contreras RJ (2010) response latency to lingual taste stimulation distinguishes neuron types within the geniculate ganglion. J Neurophysiol 103:1771–1784. https://doi.org/10.1152/jn.00785.2009

  81. 81.

    Chen X, Gabitto M, Peng Y et al (2011) A gustotopic map of taste qualities in the mammalian brain. Science 333:1262–1266. https://doi.org/10.1126/science.1204076

  82. 82.

    Roussin AT, D’Agostino AE, Fooden AM et al (2012) Taste coding in the nucleus of the solitary tract of the awake, freely licking rat. J Neurosci Off J Soc Neurosci 32:10494–10506. https://doi.org/10.1523/JNEUROSCI.1856-12.2012

  83. 83.

    Sammons JD, Weiss MS, Victor JD, Di Lorenzo PM (2016) Taste coding of complex naturalistic taste stimuli and traditional taste stimuli in the parabrachial pons of the awake, freely licking rat. J Neurophysiol 116:171–182. https://doi.org/10.1152/jn.01119.2015

  84. 84.

    Liu H, Fontanini A (2015) State dependency of chemosensory coding in the gustatory thalamus (VPMpc) of alert rats. J Neurosci 35:15479–15491. https://doi.org/10.1523/JNEUROSCI.0839-15.2015

  85. 85.

    Nomura T, Ogawa H (1985) The taste and mechanical response properties of neurons in the parvicellular part of the thalamic posteromedial ventral nucleus of the rat. Neurosci Res 3:91–105

  86. 86.

    Ogawa H, Nomura T (1988) Receptive field properties of thalamo-cortical taste relay neurons in the parvicellular part of the posteromedial ventral nucleus in rats. Exp Brain Res 73:364–370. https://doi.org/10.1007/bf00248229

  87. 87.

    Verhagen JV, Giza BK, Scott TR (2003) Responses to taste stimulation in the ventroposteromedial nucleus of the thalamus in rats. J Neurophysiol 89:265–275. https://doi.org/10.1152/jn.00870.2001

  88. 88.

    Levitan D, Lin J-Y, Wachutka J et al (2019) Single and population coding of taste in the gustatory cortex of awake mice. J Neurophysiol. https://doi.org/10.1152/jn.00357.2019

  89. 89.

    Stapleton JR, Lavine ML, Wolpert RL et al (2006) Rapid taste responses in the gustatory cortex during licking. J Neurosci Off J Soc Neurosci 26:4126–4138. https://doi.org/10.1523/JNEUROSCI.0092-06.2006

  90. 90.

    Yaxley S, Rolls ET, Sienkiewicz ZJ (1990) Gustatory responses of single neurons in the insula of the macaque monkey. J Neurophysiol 63:689–700. https://doi.org/10.1152/jn.1990.63.4.689

  91. 91.

    Fletcher ML, Ogg MC, Lu L et al (2017) Overlapping representation of primary tastes in a defined region of the gustatory cortex. J Neurosci Off J Soc Neurosci 37:7595–7605. https://doi.org/10.1523/JNEUROSCI.0649-17.2017

  92. 92.

    Lavi K, Jacobson GA, Rosenblum K, Lüthi A (2018) Encoding of conditioned taste aversion in cortico-amygdala circuits. Cell Rep 24:278–283. https://doi.org/10.1016/j.celrep.2018.06.053

  93. 93.

    Livneh Y, Ramesh RN, Burgess CR et al (2017) Homeostatic circuits selectively gate food cue responses in insular cortex. Nature 546:611–616. https://doi.org/10.1038/nature22375

  94. 94.

    Fonseca E, de Lafuente V, Simon SA, Gutierrez R (2018) Sucrose intensity coding and decision-making in rat gustatory cortices. eLife 7:e41152. https://doi.org/10.7554/eLife.41152

  95. 95.

    Gehrlach DA, Dolensek N, Klein AS et al (2019) Aversive state processing in the posterior insular cortex. Nat Neurosci 22:1424–1437. https://doi.org/10.1038/s41593-019-0469-1

  96. 96.

    Chikazoe J, Lee DH, Kriegeskorte N, Anderson AK (2019) Distinct representations of basic taste qualities in human gustatory cortex. Nat Commun 10:1048. https://doi.org/10.1038/s41467-019-08857-z

  97. 97.

    Canna A, Prinster A, Cantone E et al (2019) Intensity-related distribution of sweet and bitter taste fMRI responses in the insular cortex. Hum Brain Mapp 40:3631–3646. https://doi.org/10.1002/hbm.24621

  98. 98.

    Avery JA, Liu AG, Ingeholm JE, et al (2019) Taste quality representation in the human brain. bioRxiv 726711. https://doi.org/10.1101/726711

  99. 99.

    Porcu E, Benz K, Ball F, et al (2019) Information-based taste maps in insular cortex are shaped by stimulus concentration. Neuroscience

  100. 100.

    Peng Y, Gillis-Smith S, Jin H et al (2015) Sweet and bitter taste in the brain of awake behaving animals. Nature 527:512–515. https://doi.org/10.1038/nature15763

  101. 101.

    Spector AC, Klumpp PA, Kaplan JM (1998) Analytical issues in the evaluation of food deprivation and sucrose concentration effects on the microstructure of licking behavior in the rat. Behav Neurosci 112:678–694

  102. 102.

    Young PT, Burright RG, Tromater LJ (1963) Preferences of the white rat for solutions of sucrose and quinine hydrochloride. Am J Psychol 76:205–217

  103. 103.

    Mukherjee N, Wachutka J, Katz DB (2019) Impact of precisely-timed inhibition of gustatory cortex on taste behavior depends on single-trial ensemble dynamics. eLife 8:e45968. https://doi.org/10.7554/eLife.45968

  104. 104.

    Spector AC, Smith JC (1984) A detailed analysis of sucrose drinking in the rat. Physiol Behav 33:127–136

  105. 105.

    Berridge KC, Grill HJ (1983) Alternating ingestive and aversive consummatory responses suggest a two-dimensional analysis of palatability in rats. Behav Neurosci 97:563–573

  106. 106.

    Sclafani A (1991) Conditioned food preferences and appetite. Appetite 17:71–72

  107. 107.

    Garcia J, Lasiter PS, Bermudez-Rattoni F, Deems DA (1985) A general theory of aversion learning. Ann N Y Acad Sci 443:8–21. https://doi.org/10.1111/j.1749-6632.1985.tb27060.x

  108. 108.

    Baez-Santiago MA, Reid EE, Moran A et al (2016) Dynamic taste responses of parabrachial pontine neurons in awake rats. J Neurophysiol 115:1314–1323. https://doi.org/10.1152/jn.00311.2015

  109. 109.

    Jezzini A, Mazzucato L, Camera GL, Fontanini A (2013) Processing of hedonic and chemosensory features of taste in medial prefrontal and insular networks. J Neurosci 33:18966–18978. https://doi.org/10.1523/JNEUROSCI.2974-13.2013

  110. 110.

    Sadacca BF, Rothwax JT, Katz DB (2012) Sodium concentration coding gives way to evaluative coding in cortex and amygdala. J Neurosci 32:9999–10011. https://doi.org/10.1523/JNEUROSCI.6059-11.2012

  111. 111.

    Li JX, Yoshida T, Monk KJ, Katz DB (2013) Lateral hypothalamus contains two types of palatability-related taste responses with distinct dynamics. J Neurosci 33:9462–9473. https://doi.org/10.1523/JNEUROSCI.3935-12.2013

  112. 112.

    Jezzini A, Caruana F, Stoianov I et al (2012) Functional organization of the insula and inner perisylvian regions. Proc Natl Acad Sci USA 109:10077–10082. https://doi.org/10.1073/pnas.1200143109

  113. 113.

    Wang L, Gillis-Smith S, Peng Y et al (2018) The coding of valence and identity in the mammalian taste system. Nature 558:127–131. https://doi.org/10.1038/s41586-018-0165-4

  114. 114.

    Devineni AV, Sun B, Zhukovskaya A, Axel R (2019) Acetic acid activates distinct taste pathways in Drosophila to elicit opposing, state-dependent feeding responses. eLife 8:e47677. https://doi.org/10.7554/eLife.47677

  115. 115.

    Perez IO, Villavicencio M, Simon SA, Gutierrez R (2013) Speed and accuracy of taste identification and palatability: impact of learning, reward expectancy, and consummatory licking. Am J Physiol-Regul Integr Comp Physiol 305:R252–R270. https://doi.org/10.1152/ajpregu.00492.2012

  116. 116.

    Halpern BP (1986) Constraints imposed on taste physiology by human taste reaction time data. Neurosci Biobehav Rev 10:135–151

  117. 117.

    Wallroth R, Ohla K (2018) As soon as you taste it: evidence for sequential and parallel processing of gustatory information. eNeuro 5:e0269. https://doi.org/10.1523/ENEURO.0269-18.2018

  118. 118.

    Katz DB, Simon SA, Nicolelis MAL (2002) Taste-specific neuronal ensembles in the gustatory cortex of awake rats. J Neurosci Off J Soc Neurosci 22:1850–1857

  119. 119.

    Frank M, Pfaffmann C (1969) Taste nerve fibers: a random distribution of sensitivities to four tastes. Science 164:1183–1185. https://doi.org/10.1126/science.164.3884.1183

  120. 120.

    Kovacs P, Hajnal A (2008) Altered pontine taste processing in a rat model of obesity. J Neurophysiol 100:2145–2157. https://doi.org/10.1152/jn.01359.2007

  121. 121.

    Scott TR, Plata-Salaman CR, Smith VL, Giza BK (1991) Gustatory neural coding in the monkey cortex: stimulus intensity. J Neurophysiol 65:76–86. https://doi.org/10.1152/jn.1991.65.1.76

  122. 122.

    Rolls ET, Yaxley S, Sienkiewicz ZJ (1990) Gustatory responses of single neurons in the caudolateral orbitofrontal cortex of the macaque monkey. J Neurophysiol 64:1055–1066. https://doi.org/10.1152/jn.1990.64.4.1055

  123. 123.

    Thorpe SJ, Rolls ET, Maddison S (1983) The orbitofrontal cortex: neuronal activity in the behaving monkey. Exp Brain Res 49:93–115

  124. 124.

    Maier JX, Katz DB (2013) Neural dynamics in response to binary taste mixtures. J Neurophysiol 109:2108–2117. https://doi.org/10.1152/jn.00917.2012

  125. 125.

    Rosen AM, Di Lorenzo PM (2012) Neural coding of taste by simultaneously recorded cells in the nucleus of the solitary tract of the rat. J Neurophysiol 108:3301–3312. https://doi.org/10.1152/jn.00566.2012

  126. 126.

    Tellez LA, Perez IO, Simon SA, Gutierrez R (2012) Transitions between sleep and feeding states in rat ventral striatum neurons. J Neurophysiol 108:1739–1751. https://doi.org/10.1152/jn.00394.2012

  127. 127.

    Allen WE, Chen MZ, Pichamoorthy N, et al (2019) Thirst regulates motivated behavior through modulation of brainwide neural population dynamics. Science 364:eaav3932. https://doi.org/10.1126/science.aav3932

  128. 128.

    Green BG, Frankmann SP (1988) The effect of cooling on the perception of carbohydrate and intensive sweeteners. Physiol Behav 43:515–519. https://doi.org/10.1016/0031-9384(88)90127-8

  129. 129.

    Cruz A, Green BG (2000) Thermal stimulation of taste. Nature 403:889–892. https://doi.org/10.1038/35002581

  130. 130.

    Green BG, Nachtigal D (2015) Temperature affects human sweet taste via at least two mechanisms. Chem Senses 40:391–399. https://doi.org/10.1093/chemse/bjv021

  131. 131.

    Breza JM, Curtis KS, Contreras RJ (2006) Temperature modulates taste responsiveness and stimulates gustatory neurons in the rat geniculate ganglion. J Neurophysiol 95:674–685. https://doi.org/10.1152/jn.00793.2005

  132. 132.

    Lemon CH (2017) Modulation of taste processing by temperature. Am J Physiol-Regul Integr Comp Physiol 313:R305–R321. https://doi.org/10.1152/ajpregu.00089.2017

  133. 133.

    Lemon CH (2015) Perceptual and neural responses to sweet taste in humans and rodents. Chemosens Percept 8:46–52. https://doi.org/10.1007/s12078-015-9177-8

  134. 134.

    Talavera K, Yasumatsu K, Voets T et al (2005) Heat activation of TRPM5 underlies thermal sensitivity of sweet taste. Nature 438:1022–1025. https://doi.org/10.1038/nature04248

  135. 135.

    Wilson DM, Lemon CH (2014) Temperature systematically modifies neural activity for sweet taste. J Neurophysiol 112:1667–1677. https://doi.org/10.1152/jn.00368.2014

  136. 136.

    Li J, Lemon CH (2015) Influence of stimulus and oral adaptation temperature on gustatory responses in central taste-sensitive neurons. J Neurophysiol 113:2700–2712. https://doi.org/10.1152/jn.00736.2014

  137. 137.

    Liman ER (2007) TRPM5 and taste transduction. In: Flockerzi V, Nilius B (eds) Transient receptor potential (TRP) channels. Springer, Berlin Heidelberg, Berlin, Heidelberg, pp 287–298

  138. 138.

    Kwon O, Kim KW, Kim M-S (2016) Leptin signalling pathways in hypothalamic neurons. Cell Mol Life Sci CMLS 73:1457–1477. https://doi.org/10.1007/s00018-016-2133-1

  139. 139.

    Meister B (2000) Control of food intake via leptin receptors in the hypothalamus. Vitam Horm 59:265–304

  140. 140.

    Kawai K, Sugimoto K, Nakashima K et al (2000) Leptin as a modulator of sweet taste sensitivities in mice. Proc Natl Acad Sci 97:11044–11049. https://doi.org/10.1073/pnas.190066697

  141. 141.

    Shigemura N, Ohta R, Kusakabe Y et al (2004) Leptin modulates behavioral responses to sweet substances by influencing peripheral taste structures. Endocrinology 145:839–847. https://doi.org/10.1210/en.2003-0602

  142. 142.

    Ninomiya Y, Sako N, Imai Y (1995) Enhanced gustatory neural responses to sugars in the diabetic db/db mouse. Am J Physiol-Regul Integr Comp Physiol 269:R930–R937. https://doi.org/10.1152/ajpregu.1995.269.4.R930

  143. 143.

    Yoshida R, Niki M, Jyotaki M et al (2013) Modulation of sweet responses of taste receptor cells. Semin Cell Dev Biol 24:226–231. https://doi.org/10.1016/j.semcdb.2012.08.004

  144. 144.

    Niki M, Jyotaki M, Yoshida R et al (2015) Modulation of sweet taste sensitivities by endogenous leptin and endocannabinoids in mice. J Physiol 593:2527–2545. https://doi.org/10.1113/JP270295

  145. 145.

    Nakamura Y, Sanematsu K, Ohta R et al (2008) Diurnal variation of human sweet taste recognition thresholds is correlated with plasma leptin levels. Diabetes 57:2661–2665. https://doi.org/10.2337/db07-1103

  146. 146.

    Han P, Keast RSJ, Roura E (2017) Salivary leptin and TAS1R2/TAS1R3 polymorphisms are related to sweet taste sensitivity and carbohydrate intake from a buffet meal in healthy young adults. Br J Nutr 118:763–770. https://doi.org/10.1017/S0007114517002872

  147. 147.

    Sanematsu K, Nakamura Y, Nomura M et al (2018) Diurnal variation of sweet taste recognition thresholds is absent in overweight and obese humans. Nutrients 10:297. https://doi.org/10.3390/nu10030297

  148. 148.

    Fujita T (1991) Taste cells in the gut and on the tongue. Their common, paraneuronal features. Physiol Behav 49:883–885. https://doi.org/10.1016/0031-9384(91)90198-W

  149. 149.

    Hass N, Schwarzenbacher K, Breer H (2010) T1R3 is expressed in brush cells and ghrelin-producing cells of murine stomach. Cell Tissue Res 339:493–504. https://doi.org/10.1007/s00441-009-0907-6

  150. 150.

    Höfer D, Drenckhahn D (1998) Identification of the taste cell G-protein, alpha-gustducin, in brush cells of the rat pancreatic duct system. Histochem Cell Biol 110:303–309

  151. 151.

    Jang H-J, Kokrashvili Z, Theodorakis MJ et al (2007) Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci USA 104:15069–15074. https://doi.org/10.1073/pnas.0706890104

  152. 152.

    Margolskee RF, Dyer J, Kokrashvili Z et al (2007) T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1. Proc Natl Acad Sci USA 104:15075–15080. https://doi.org/10.1073/pnas.0706678104

  153. 153.

    Lee RJ, Kofonow JM, Rosen PL et al (2014) Bitter and sweet taste receptors regulate human upper respiratory innate immunity. J Clin Invest 124:1393–1405. https://doi.org/10.1172/JCI72094

  154. 154.

    Tizzano M, Cristofoletti M, Sbarbati A, Finger TE (2011) Expression of taste receptors in Solitary Chemosensory Cells of rodent airways. BMC Pulm Med 11:3. https://doi.org/10.1186/1471-2466-11-3

  155. 155.

    Kohno D, Koike M, Ninomiya Y et al (2016) Sweet taste receptor serves to activate glucose- and leptin-responsive neurons in the hypothalamic arcuate nucleus and participates in glucose responsiveness. Front Neurosci 10:502. https://doi.org/10.3389/fnins.2016.00502

  156. 156.

    Ren X, Zhou L, Terwilliger R et al (2009) Sweet taste signaling functions as a hypothalamic glucose sensor. Front Integr Neurosci 3:12. https://doi.org/10.3389/neuro.07.012.2009

  157. 157.

    Masubuchi Y, Nakagawa Y, Ma J et al (2013) A novel regulatory function of sweet taste-sensing receptor in adipogenic differentiation of 3T3-L1 cells. PLoS One 8:e54500. https://doi.org/10.1371/journal.pone.0054500

  158. 158.

    Simon BR, Parlee SD, Learman BS et al (2013) Artificial sweeteners stimulate adipogenesis and suppress lipolysis independently of sweet taste receptors. J Biol Chem 288:32475–32489. https://doi.org/10.1074/jbc.M113.514034

  159. 159.

    Lizunkova P, Enuwosa E, Chichger H (2019) Activation of the sweet taste receptor T1R3 by sucralose attenuates VEGF-induced vasculogenesis in a cell model of the retinal microvascular endothelium. Graefes Arch Clin Exp Ophthalmol 257:71–81. https://doi.org/10.1007/s00417-018-4157-8

  160. 160.

    Gong T, Wei Q, Mao D, Shi F (2016) Expression patterns of taste receptor type 1 subunit 3 and α-gustducin in the mouse testis during development. Acta Histochem 118:20–30. https://doi.org/10.1016/j.acthis.2015.11.001

  161. 161.

    Kiuchi S, Yamada T, Kiyokawa N et al (2006) Genomic structure of swine taste receptor family 1 member 3, TAS1R3, and its expression in tissues. Cytogenet Genome Res 115:51–61. https://doi.org/10.1159/000094801

  162. 162.

    Li F (2013) Taste perception: from the tongue to the testis. MHR Basic Sci Reprod Med 19:349–360. https://doi.org/10.1093/molehr/gat009

  163. 163.

    Max M, Shanker YG, Huang L et al (2001) Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac. Nat Genet 28:58–63. https://doi.org/10.1038/88270

  164. 164.

    Foster SR, Porrello ER, Purdue B et al (2013) Expression, regulation and putative nutrient-sensing function of taste GPCRs in the heart. PLoS One 8:e64579. https://doi.org/10.1371/journal.pone.0064579

  165. 165.

    Kochem M (2017) Type 1 taste receptors in taste and metabolism. Ann Nutr Metab 70(Suppl 3):27–36. https://doi.org/10.1159/000478760

  166. 166.

    Nakagawa Y, Nagasawa M, Yamada S et al (2009) Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion. PLoS One 4:e5106. https://doi.org/10.1371/journal.pone.0005106

  167. 167.

    Taniguchi K (2004) Expression of the sweet receptor protein, T1R3, in the human liver and pancreas. J Vet Med Sci 66:1311–1314. https://doi.org/10.1292/jvms.66.1311

  168. 168.

    Elliott RA, Kapoor S, Tincello DG (2011) Expression and distribution of the sweet taste receptor isoforms T1R2 and T1R3 in human and rat bladders. J Urol 186:2455–2462. https://doi.org/10.1016/j.juro.2011.07.083

  169. 169.

    Meyer D, Voigt A, Widmayer P et al (2012) Expression of Tas1 taste receptors in mammalian spermatozoa: functional role of Tas1r1 in regulating basal Ca2+ and cAMP concentrations in spermatozoa. PLoS One 7:e32354. https://doi.org/10.1371/journal.pone.0032354

  170. 170.

    Kyriazis GA, Soundarapandian MM, Tyrberg B (2012) Sweet taste receptor signaling in beta cells mediates fructose-induced potentiation of glucose-stimulated insulin secretion. Proc Natl Acad Sci USA 109:E524–E532. https://doi.org/10.1073/pnas.1115183109

  171. 171.

    Oliveira-Maia AJ, Roberts CD, Walker QD et al (2011) Intravascular food reward. PLOS One 6:e24992. https://doi.org/10.1371/journal.pone.0024992

  172. 172.

    Qu T, Han W, Niu J et al (2019) On the roles of the Duodenum and the Vagus nerve in learned nutrient preferences. Appetite 139:145–151. https://doi.org/10.1016/j.appet.2019.04.014

  173. 173.

    Tellez LA, Han W, Zhang X et al (2016) Separate circuitries encode the hedonic and nutritional values of sugar. Nat Neurosci 19:465–470. https://doi.org/10.1038/nn.4224

  174. 174.

    Holman GL (1969) Intragastric reinforcement effect. J Comp Physiol Psychol 69:432–441. https://doi.org/10.1037/h0028233

  175. 175.

    Sclafani A, Cardieri C, Tucker K et al (1993) Intragastric glucose but not fructose conditions robust flavor preferences in rats. Am J Physiol-Regul Integr Comp Physiol 265:R320–R325. https://doi.org/10.1152/ajpregu.1993.265.2.R320

  176. 176.

    Zhang L, Han W, Lin C et al (2018) Sugar metabolism regulates flavor preferences and portal glucose sensing. Front Integr Neurosci. https://doi.org/10.3389/fnint.2018.00057

  177. 177.

    Grill HJ, Norgren R (1978) Chronically decerebrate rats demonstrate satiation but not bait shyness. Science 201:267–269. https://doi.org/10.1126/science.663655

  178. 178.

    Berridge KC (2009) Wanting and liking: observations from the neuroscience and psychology laboratory. Inq Oslo Nor 52:378. https://doi.org/10.1080/00201740903087359

  179. 179.

    Ackroff K, Yiin Y-M, Sclafani A (2010) Post-oral infusion sites that support glucose-conditioned flavor preferences in rats. Physiol Behav 99:402–411. https://doi.org/10.1016/j.physbeh.2009.12.012

  180. 180.

    Sclafani A, Ackroff K (2019) Commentary: sugar metabolism regulates flavor preferences and portal glucose sensing. Front Integr Neurosci. https://doi.org/10.3389/fnint.2019.00004

  181. 181.

    Han W, Tellez LA, Niu J et al (2016) Striatal dopamine links gastrointestinal rerouting to altered sweet appetite. Cell Metab 23:103–112. https://doi.org/10.1016/j.cmet.2015.10.009

  182. 182.

    Sclafani A, Glass DS, Margolskee RF, Glendinning JI (2010) Gut T1R3 sweet taste receptors do not mediate sucrose-conditioned flavor preferences in mice. Am J Physiol Regul Integr Comp Physiol 299:R1643–R1650. https://doi.org/10.1152/ajpregu.00495.2010

  183. 183.

    Zukerman S, Ackroff K, Sclafani A (2013) Post-oral appetite stimulation by sugars and nonmetabolizable sugar analogs. Am J Physiol-Regul Integr Comp Physiol 305:R840–R853. https://doi.org/10.1152/ajpregu.00297.2013

  184. 184.

    Ren X, Ferreira JG, Zhou L et al (2010) Nutrient selection in the absence of taste receptor signaling. J Neurosci 30:8012–8023. https://doi.org/10.1523/JNEUROSCI.5749-09.2010

  185. 185.

    Strubbe JH, Steffens AB (1977) Blood glucose levels in portal and peripheral circulation and their relation to food intake in the rat. Physiol Behav 19:303–307. https://doi.org/10.1016/0031-9384(77)90342-0

  186. 186.

    Tordoff MG, Friedman MI (1986) Hepatic portal glucose infusions decrease food intake and increase food preference. Am J Physiol 251:R192–R196. https://doi.org/10.1152/ajpregu.1986.251.1.R192

  187. 187.

    Berthoud H-R (2004) Anatomy and function of sensory hepatic nerves. Anat Rec A Discov Mol Cell Evol Biol 280A:827–835. https://doi.org/10.1002/ar.a.20088

  188. 188.

    Han W, Tellez LA, Perkins MH et al (2018) A neural circuit for gut-induced reward. Cell 175:887–888. https://doi.org/10.1016/j.cell.2018.10.018

  189. 189.

    Sclafani A, Lucas F (1996) Abdominal vagotomy does not block carbohydrate-conditioned flavor preferences in rats. Physiol Behav 60:447–453. https://doi.org/10.1016/S0031-9384(96)80018-7

  190. 190.

    Uematsu A, Tsurugizawa T, Uneyama H, Torii K (2010) Brain–gut communication via vagus nerve modulates conditioned flavor preference. Eur J Neurosci 31:1136–1143. https://doi.org/10.1111/j.1460-9568.2010.07136.x

  191. 191.

    Worthington JJ, Reimann F, Gribble FM (2018) Enteroendocrine cells-sensory sentinels of the intestinal environment and orchestrators of mucosal immunity. Mucosal Immunol 11:3–20. https://doi.org/10.1038/mi.2017.73

  192. 192.

    Kaelberer MM, Buchanan KL, Klein ME et al (2018) A gut-brain neural circuit for nutrient sensory transduction. Science 361:eaat5236. https://doi.org/10.1126/science.aat5236

  193. 193.

    Domingos AI, Vaynshteyn J, Voss HU et al (2011) Leptin regulates the reward value of nutrient. Nat Neurosci 14:1562–1568. https://doi.org/10.1038/nn.2977

  194. 194.

    Hajnal A, Smith GP, Norgren R (2004) Oral sucrose stimulation increases accumbens dopamine in the rat. Am J Physiol Regul Integr Comp Physiol 286:R31–R37. https://doi.org/10.1152/ajpregu.00282.2003

  195. 195.

    Norgren R, Hajnal A, Mungarndee SS (2006) Gustatory reward and the nucleus accumbens. Physiol Behav 89:531–535. https://doi.org/10.1016/j.physbeh.2006.05.024

  196. 196.

    Klawonn AM, Malenka RC (2019) Nucleus accumbens modulation in reward and aversion. Cold Spring Harb Symp Quant Biol. https://doi.org/10.1101/sqb.2018.83.037457

  197. 197.

    Thanarajah SE, Backes H, DiFeliceantonio AG et al (2019) Food intake recruits orosensory and post-ingestive dopaminergic circuits to affect eating desire in humans. Cell Metab 29:695.e4–706.e4. https://doi.org/10.1016/j.cmet.2018.12.006

  198. 198.

    Wang G-J, Volkow ND, Logan J et al (2001) Brain dopamine and obesity. The Lancet 357:354–357. https://doi.org/10.1016/S0140-6736(00)03643-6

  199. 199.

    Wiss DA, Avena N, Rada P (2018) Sugar addiction: from evolution to revolution. Front Psychiatry. https://doi.org/10.3389/fpsyt.2018.00545

  200. 200.

    Johnson PM, Kenny PJ (2010) Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci 13:635–641. https://doi.org/10.1038/nn.2519

  201. 201.

    Blum K, Thanos PK, Gold MS (2014) Dopamine and glucose, obesity, and reward deficiency syndrome. Front Psychol. https://doi.org/10.3389/fpsyg.2014.00919

  202. 202.

    Stice E, Yokum S, Blum K, Bohon C (2010) Weight gain is associated with reduced striatal response to palatable food. J Neurosci 30:13105–13109. https://doi.org/10.1523/JNEUROSCI.2105-10.2010

  203. 203.

    Pritchett CE, Hajnal A (2011) Obesogenic diets may differentially alter dopamine control of sucrose and fructose intake in rats. Physiol Behav 104:111–116. https://doi.org/10.1016/j.physbeh.2011.04.048

  204. 204.

    DiFeliceantonio AG, Small DM (2019) Dopamine and diet-induced obesity. Nat Neurosci 22:1–2. https://doi.org/10.1038/s41593-018-0304-0

  205. 205.

    Shoar S, Saber AA (2017) Long-term and midterm outcomes of laparoscopic sleeve gastrectomy versus Roux-en-Y gastric bypass: a systematic review and meta-analysis of comparative studies. Surg Obes Relat Dis Off J Am Soc Bariatr Surg 13:170–180. https://doi.org/10.1016/j.soard.2016.08.011

  206. 206.

    Mathes CM (2019) Taste- and flavor-guided behaviors following Roux-en-Y gastric bypass in rodent models. Appetite. https://doi.org/10.1016/j.appet.2019.104422

  207. 207.

    Hankir MK, Seyfried F, Hintschich CA et al (2017) Gastric bypass surgery recruits a gut PPAR-α-striatal D1R pathway to reduce fat appetite in obese rats. Cell Metab 25:335–344. https://doi.org/10.1016/j.cmet.2016.12.006

  208. 208.

    Tellez LA, Medina S, Han W et al (2013) A gut lipid messenger links excess dietary fat to dopamine deficiency. Science 341:800–802. https://doi.org/10.1126/science.1239275

  209. 209.

    Tsouristakis AI, Febres G, McMahon DJ et al (2019) Long-term modulation of appetitive hormones and sweet cravings after adjustable gastric banding and Roux-en-Y gastric bypass. Obes Surg. https://doi.org/10.1007/s11695-019-04111-z

  210. 210.

    Sternson SM, Eiselt A-K (2017) Three pillars for the neural control of appetite. Annu Rev Physiol 79:401–423. https://doi.org/10.1146/annurev-physiol-021115-104948

  211. 211.

    Burnett CJ, Li C, Webber E et al (2016) Hunger-driven motivational state competition. Neuron 92:187–201. https://doi.org/10.1016/j.neuron.2016.08.032

  212. 212.

    Aponte Y, Atasoy D, Sternson SM (2011) AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training. Nat Neurosci 14:351–355. https://doi.org/10.1038/nn.2739

  213. 213.

    Jennings JH, Ung RL, Resendez SL et al (2015) Visualizing hypothalamic network dynamics for appetitive and consummatory behaviors. Cell 160:516–527. https://doi.org/10.1016/j.cell.2014.12.026

  214. 214.

    Navarro M, Olney JJ, Burnham NW et al (2016) Lateral hypothalamus gabaergic neurons modulate consummatory behaviors regardless of the caloric content or biological relevance of the consumed stimuli. Neuropsychopharmacology 41:1505–1512. https://doi.org/10.1038/npp.2015.304

  215. 215.

    Nieh EH, Vander Weele CM, Matthews GA et al (2016) Inhibitory input from the lateral hypothalamus to the ventral tegmental area disinhibits dopamine neurons and promotes behavioral activation. Neuron 90:1286–1298. https://doi.org/10.1016/j.neuron.2016.04.035

  216. 216.

    de Jong JW, Afjei SA, Pollak Dorocic I et al (2019) A neural circuit mechanism for encoding aversive stimuli in the mesolimbic dopamine system. Neuron 101:133.e7–151.e7. https://doi.org/10.1016/j.neuron.2018.11.005

  217. 217.

    Rossi MA, Basiri ML, McHenry JA et al (2019) Obesity remodels activity and transcriptional state of a lateral hypothalamic brake on feeding. Science 364:1271–1274. https://doi.org/10.1126/science.aax1184

  218. 218.

    Sternson SM (2016) Hunger: the carrot and the stick. Mol Metab 5:1–2. https://doi.org/10.1016/j.molmet.2015.10.002

  219. 219.

    Su Z, Alhadeff AL, Betley JN (2017) Nutritive, post-ingestive signals are the primary regulators of AgRP neuron activity. Cell Rep 21:2724–2736. https://doi.org/10.1016/j.celrep.2017.11.036

  220. 220.

    Beutler LR, Chen Y, Ahn JS et al (2017) Dynamics of gut-brain communication underlying hunger. Neuron 96:461.e5–475.e5. https://doi.org/10.1016/j.neuron.2017.09.043

  221. 221.

    Chen Y, Lin Y-C, Zimmerman CA et al (2016) Hunger neurons drive feeding through a sustained, positive reinforcement signal. eLife 5. https://doi.org/10.7554/eLife.18640

  222. 222.

    Krashes MJ, Koda S, Ye C et al (2011) Rapid, reversible activation of AgRP neurons drives feeding behavior in mice. J Clin Invest 121:1424–1428. https://doi.org/10.1172/JCI46229

  223. 223.

    Luquet S, Perez FA, Hnasko TS, Palmiter RD (2005) NPY/AgRP neurons are essential for feeding in adult mice but can be ablated in neonates. Science 310:683–685. https://doi.org/10.1126/science.1115524

  224. 224.

    Atasoy D, Betley JN, Su HH, Sternson SM (2012) Deconstruction of a neural circuit for hunger. Nature 488:172–177. https://doi.org/10.1038/nature11270

  225. 225.

    Betley JN, Xu S, Cao ZFH et al (2015) Neurons for hunger and thirst transmit a negative-valence teaching signal. Nature 521:180–185. https://doi.org/10.1038/nature14416

  226. 226.

    Mandelblat-Cerf Y, Ramesh RN, Burgess CR, et al (2015) Arcuate hypothalamic AgRP and putative POMC neurons show opposite changes in spiking across multiple timescales. eLife 4:e07122. https://doi.org/10.7554/eLife.07122

  227. 227.

    Rau AR, Hentges ST (2017) The relevance of AgRP neuron-derived GABA inputs to POMC neurons differs for spontaneous and evoked release. J Neurosci 37:7362–7372. https://doi.org/10.1523/JNEUROSCI.0647-17.2017

  228. 228.

    Wei Q, Krolewski DM, Moore S et al (2018) Uneven balance of power between hypothalamic peptidergic neurons in the control of feeding. Proc Natl Acad Sci 115:E9489–E9498. https://doi.org/10.1073/pnas.1802237115

  229. 229.

    Weingarten HP (1984) Meal initiation controlled by learned cues: basic behavioral properties. Appetite 5:147–158

  230. 230.

    Robinson MJ, Burghardt PR, Patterson CM et al (2015) Individual differences in cue-induced motivation and striatal systems in rats susceptible to diet-induced obesity. Neuropsychopharmacology 40:2113–2123. https://doi.org/10.1038/npp.2015.71

  231. 231.

    Burger KS, Stice E (2014) Greater striatopallidal adaptive coding during cue–reward learning and food reward habituation predict future weight gain. NeuroImage 99:122–128. https://doi.org/10.1016/j.neuroimage.2014.05.066

  232. 232.

    Reppucci CJ, Petrovich GD (2012) Learned food-cue stimulates persistent feeding in sated rats. Appetite 59:437–447. https://doi.org/10.1016/j.appet.2012.06.007

  233. 233.

    Derman RC, Ferrario CR (2018) Junk-food enhances conditioned food cup approach to a previously established food cue, but does not alter cue potentiated feeding; implications for the effects of palatable diets on incentive motivation. Physiol Behav 192:145–157. https://doi.org/10.1016/j.physbeh.2018.03.012

  234. 234.

    Denis RGP, Joly-Amado A, Webber E et al (2015) Palatability can drive feeding independent of AgRP neurons. Cell Metab 22:646–657. https://doi.org/10.1016/j.cmet.2015.07.011

  235. 235.

    O’Connor EC, Kremer Y, Lefort S et al (2015) Accumbal D1R neurons projecting to lateral hypothalamus authorize feeding. Neuron 88:553–564. https://doi.org/10.1016/j.neuron.2015.09.038

  236. 236.

    Prado L, Luis-Islas J, Sandoval OI et al (2016) Activation of glutamatergic fibers in the anterior NAc shell modulates reward activity in the aNAcSh, the lateral hypothalamus, and medial prefrontal cortex and transiently stops feeding. J Neurosci 36:12511–12529. https://doi.org/10.1523/JNEUROSCI.1605-16.2016

  237. 237.

    Mogenson GJ, Jones DL, Yim CY (1980) From motivation to action: functional interface between the limbic system and the motor system. Prog Neurobiol 14:69–97. https://doi.org/10.1016/0301-0082(80)90018-0

  238. 238.

    Kalyanasundar B, Perez CI, Luna A et al (2015) D1 and D2 antagonists reverse the effects of appetite suppressants on weight loss, food intake, locomotion, and rebalance spiking inhibition in the rat NAc shell. J Neurophysiol 114:585–607. https://doi.org/10.1152/jn.00012.2015

  239. 239.

    Rothman RB, Baumann MH (2006) Balance between dopamine and serotonin release modulates behavioral effects of amphetamine-type drugs. Ann N Y Acad Sci 1074:245–260. https://doi.org/10.1196/annals.1369.064

  240. 240.

    Britt JP, Benaliouad F, McDevitt RA et al (2012) Synaptic and behavioral profile of multiple glutamatergic inputs to the nucleus accumbens. Neuron 76:790–803. https://doi.org/10.1016/j.neuron.2012.09.040

  241. 241.

    Reed SJ, Lafferty CK, Mendoza JA et al (2018) Coordinated reductions in excitatory input to the nucleus accumbens underlie food consumption. Neuron 99:1260.e4–1273.e4. https://doi.org/10.1016/j.neuron.2018.07.051

  242. 242.

    Valenstein ES, Cox VC, Kakolewski JW (1968) Modification of motivated behavior elicited by electrical stimulation of the hypothalamus. Science 159:1119–1121. https://doi.org/10.1126/science.159.3819.1119

  243. 243.

    Frank RA, Preshaw RL, Stutz RM, Valenstein ES (1982) Lateral hypothalamic stimulation: stimulus-bound eating and self-deprivation. Physiol Behav 29:17–21. https://doi.org/10.1016/0031-9384(82)90359-6

  244. 244.

    Anand BK, Brobeck JR (1951) Hypothalamic control of food intake in rats and cats. Yale J Biol Med 24:123–140

  245. 245.

    de Lecea L (2015) Optogenetic control of hypocretin (orexin) neurons and arousal circuits. Curr Top Behav Neurosci 25:367–378. https://doi.org/10.1007/7854_2014_364

  246. 246.

    Stamatakis AM, Swieten MV, Basiri ML et al (2016) Lateral hypothalamic area glutamatergic neurons and their projections to the lateral habenula regulate feeding and reward. J Neurosci 36:302–311. https://doi.org/10.1523/JNEUROSCI.1202-15.2016

  247. 247.

    You ZB, Chen YQ, Wise RA (2001) Dopamine and glutamate release in the nucleus accumbens and ventral tegmental area of rat following lateral hypothalamic self-stimulation. Neuroscience 107:629–639. https://doi.org/10.1016/s0306-4522(01)00379-7

  248. 248.

    Zhang X, van den Pol AN (2017) Rapid binge-like eating and body weight gain driven by zona incerta GABA neuron activation. Science 356:853–859. https://doi.org/10.1126/science.aam7100

  249. 249.

    WHO. Sugars intake for adults and children. In: WHO. http://www.who.int/nutrition/publications/guidelines/sugars_intake/en/. Accessed 16 Aug 2019

  250. 250.

    Bartoshuk LM, Duffy VB, Hayes JE et al (2006) Psychophysics of sweet and fat perception in obesity: problems, solutions and new perspectives. Philos Trans R Soc Lond B Biol Sci 361:1137–1148. https://doi.org/10.1098/rstb.2006.1853

  251. 251.

    Berthoud H-R, Zheng H (2012) Modulation of taste responsiveness and food preference by obesity and weight loss. Physiol Behav 107:527–532. https://doi.org/10.1016/j.physbeh.2012.04.004

  252. 252.

    May CE, Vaziri A, Lin YQ et al (2019) High dietary sugar reshapes sweet taste to promote feeding behavior in Drosophila melanogaster. Cell Rep 27:1675.e7–1685.e7. https://doi.org/10.1016/j.celrep.2019.04.027

  253. 253.

    Overberg J, Hummel T, Krude H, Wiegand S (2012) Differences in taste sensitivity between obese and non-obese children and adolescents. Arch Dis Child 97:1048–1052. https://doi.org/10.1136/archdischild-2011-301189

  254. 254.

    Pasquet P, Frelut ML, Simmen B et al (2007) Taste perception in massively obese and in non-obese adolescents. Int J Pediatr Obes IJPO Off J Int Assoc Study Obes 2:242–248. https://doi.org/10.1080/17477160701440521

  255. 255.

    Proserpio C, Laureati M, Bertoli S et al (2016) Determinants of obesity in Italian adults: the role of taste sensitivity, food liking, and food neophobia. Chem Senses 41:169–176. https://doi.org/10.1093/chemse/bjv072

  256. 256.

    Sartor F, Donaldson LF, Markland DA et al (2011) Taste perception and implicit attitude toward sweet related to body mass index and soft drink supplementation. Appetite 57:237–246. https://doi.org/10.1016/j.appet.2011.05.107

  257. 257.

    Weiss MS, Hajnal A, Czaja K, Di Lorenzo PM (2019) Taste responses in the nucleus of the solitary tract of awake obese rats are blunted compared with those in lean rats. Front Integr Neurosci. https://doi.org/10.3389/fnint.2019.00035

  258. 258.

    Kaufman A, Choo E, Koh A, Dando R (2018) Inflammation arising from obesity reduces taste bud abundance and inhibits renewal. PLoS Biol 16:e2001959. https://doi.org/10.1371/journal.pbio.2001959

  259. 259.

    Scott K (2018) Gustatory processing in Drosophila melanogaster. Annu Rev Entomol 63:15–30. https://doi.org/10.1146/annurev-ento-020117-043331

  260. 260.

    Hanover JA (2010) Epigenetics gets sweeter: O-GlcNAc joins the “Histone Code”. Chem Biol 17:1272–1274. https://doi.org/10.1016/j.chembiol.2010.12.001

  261. 261.

    Hardivillé S, Hart GW (2014) Nutrient regulation of signaling, transcription, and cell physiology by O-GlcNAcylation. Cell Metab 20:208–213. https://doi.org/10.1016/j.cmet.2014.07.014

  262. 262.

    Togo J, Hu S, Li M et al (2019) Impact of dietary sucrose on adiposity and glucose homeostasis in C57BL/6J mice depends on mode of ingestion: liquid or solid. Mol Metab. https://doi.org/10.1016/j.molmet.2019.05.010

  263. 263.

    Malik VS, Willett WC, Hu FB (2013) Global obesity: trends, risk factors and policy implications. Nat Rev Endocrinol 9:13–27. https://doi.org/10.1038/nrendo.2012.199

  264. 264.

    Barquera S, Hernandez-Barrera L, Tolentino ML et al (2008) Energy intake from beverages is increasing among Mexican adolescents and adults. J Nutr 138:2454–2461. https://doi.org/10.3945/jn.108.092163

  265. 265.

    Cassady BA, Considine RV, Mattes RD (2012) Beverage consumption, appetite, and energy intake: what did you expect? Am J Clin Nutr 95:587–593. https://doi.org/10.3945/ajcn.111.025437

  266. 266.

    Shearrer GE, O’Reilly GA, Belcher BR et al (2016) The impact of sugar sweetened beverage intake on hunger and satiety in minority adolescents. Appetite 97:43–48. https://doi.org/10.1016/j.appet.2015.11.015

  267. 267.

    Collin LJ, Judd S, Safford M et al (2019) Association of sugary beverage consumption with mortality risk in US adults: a secondary analysis of data from the regards study. JAMA Netw Open 2:e193121–e193121. https://doi.org/10.1001/jamanetworkopen.2019.3121

  268. 268.

    Jiantao Ma, McKeown Nicola M, Shih-Jen Hwang et al (2016) Sugar-Sweetened beverage consumption is associated with change of visceral adipose tissue over 6 years of follow-up. Circulation 133:370–377. https://doi.org/10.1161/CIRCULATIONAHA.115.018704

  269. 269.

    Reed DR, Mainland JD, Arayata CJ (2019) Sensory nutrition: the role of taste in the reviews of commercial food products. Physiol Behav 209:112579. https://doi.org/10.1016/j.physbeh.2019.112579

  270. 270.

    Temussi PA (2002) Why are sweet proteins sweet? Interaction of brazzein, monellin and thaumatin with the T1R2-T1R3 receptor. FEBS Lett 526:1–4. https://doi.org/10.1016/s0014-5793(02)03155-1

Download references


This project was supported in part by Productos Medix 3247, Fundación Miguel Alemán, Cátedra Marcos Moshinsky, CONACyT Grants Fronteras de la Ciencia 63, and Problemas Nacionales 464 (R.G.). We thank  Professor Carlos Cerda for help in Fig. 1. We also thank Professors Stephen Roper, Luis Tellez, Diego Bohorquez, and Monica Hernandez-Luna for their perceptive comments.

Author information

Correspondence to Ranier Gutierrez.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Gutierrez, R., Fonseca, E. & Simon, S.A. The neuroscience of sugars in taste, gut-reward, feeding circuits, and obesity. Cell. Mol. Life Sci. (2020). https://doi.org/10.1007/s00018-020-03458-2

Download citation


  • Sugars
  • Sweetness
  • Hedonic taste value
  • Nutritional value
  • Gut-reward
  • AgRP
  • LHA GABA neurons
  • Obesity