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

Abstract

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.

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Fig. 1

Adapted from [270]

Fig. 2

Figure with permission from [39]

Fig. 3
Fig. 4

Reprinted with permission from [8] and [71]

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From [217]

Abbreviations

5-HT:

5-Hydroxytryptamine or serotonin

AgRP:

Agouti-related protein

aIC:

Anterior insular cortex

ARC:

Arcuate nucleus of the hypothalamus

ATD:

Amino-terminal domain

BLA:

Basolateral amygdala

BNST:

Bed nucleus of the stria terminalis

CALHM1/3:

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

CCK:

Cholecystokinin

Cdh4:

Cadherin 4

CeA:

Central amygdala

ChR2:

Channelrhodopsin-2

CN:

Cranial nerve

CNS:

Central nervous system

CRD:

Cystein-rich domain

CT:

Chorda tympani

DA:

Dopamine

DAG:

Diacylglycerol

DAT:

Dopamine transporter promotor

DS:

Dorsal striatum

EEC:

Enteroendocrine cells

Egr2:

Early growth response 2

ENaC:

Epithelial Na+ channel

GG:

Geniculate ganglion

GIP:

Glucose-dependent insulinotropic peptide

GLP-1:

Glucagon-like peptide-1

GPN:

Sensory branch of the glossopharyngeal nerve

IC:

Insular cortex

IG:

Intragastric

IP3 :

Inositol triphosphate

IP3R3:

Inositol 1,4,5-trisphosphate receptor type 3

iPG:

Inferior petrosal ganglion

GLUT4:

Glucose transporter 4

GPCR:

G-protein coupled receptor

GPN:

Sensory branch of the glossopharyngeal nerve

GSP:

Great superficial petrosal nerve

HFD:

High fat diet

IX:

Ninth glossopharyngeal cranial nerve

latNAc:

Lateral nucleus accumbens

latVTA:

Lateral ventral tegmental area

LHA:

Lateral hypothalamic area

LHAVgat+ :

Lateral hypothalamic area neuron expressing vesicular GABA transporter

LHAVglut2+ :

Lateral hypothalamic area neuron expressing vesicular glutamatergic transporter 2

MCH:

Melanin-concentrating hormone

MSN:

Medium spiny neuron

MSND1+ :

Medium spiny neuron expressing dopamine D1 receptor

MSND2+ :

Medium spiny neuron expressing dopamine D2 receptor

NAcSh:

Nucleus accumbens shell

NG:

Nodose ganglion

NTS:

Nucleus tractus solitarius

OEA:

Oleoylethanolamide

OFC:

Orbitofrontal cortex

OTOP1:

Otopetrin-1

Ox:

Orexin

PBN:

Parabrachial nucleus

Pdyn:

Prodynorphin gene

Penk:

Proenkephalin gene

pIC:

Posterior insular cortex

PIP2 :

Phosphatidylinositol 4,5-bisphosphate

POMC:

Proopiomelanocortin protein

PPAR-α:

Peroxisome proliferator-associated receptor-α

PVH:

Paraventricular hypothalamus

PVT:

Paraventricular thalamus

PYY:

Peptide YY

RASSL:

Receptors activated solely by synthetic ligands

rNTS:

Rostral portion of the nucleus tractus solitarius

SGLT1:

Sodium-glucose linked transporter 1

SLN:

Superior laryngeal branch

SNpc:

Substantia nigra pars compacta

spon1:

Spondin-1 gene

SSB:

Sugar-sweetened beverages

tas1r3:

Taste 1 receptor member 3 gene

TMD:

Transmembrane domain

TRC:

Taste receptor cell

TRPM4:

Transient receptor potential cation channel subfamily M member 4

TRPM5:

Transient receptor potential cation channel subfamily M member 5

VFD:

Venus flytrap domain

vHipp:

Ventral hippocampus

VII:

Seventh facial cranial nerve

vmNAc:

Ventromedial nucleus accumbens

vmVTA:

Ventromedial ventral tegmental area

VPMpc:

Parvocellular portion of the ventroposteromedial thalamus

VS:

Ventral striatum

VTA:

Ventral tegmental area

VTAGABA+ :

GABAergic interneurons in the ventral tegmental area

X:

CN10th vagus nerve

ZI:

Zona incerta

References

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  6. 6.

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

    Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. 14.

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. 49.

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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  56. 56.

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

    Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  72. 72.

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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  79. 79.

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

    Article  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  106. 106.

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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  116. 116.

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

    Article  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  123. 123.

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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  129. 129.

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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Chapter  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  139. 139.

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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  174. 174.

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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed Central  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  229. 229.

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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  244. 244.

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

    PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

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.

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Gutierrez, R., Fonseca, E. & Simon, S.A. The neuroscience of sugars in taste, gut-reward, feeding circuits, and obesity. Cell. Mol. Life Sci. 77, 3469–3502 (2020). https://doi.org/10.1007/s00018-020-03458-2

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Keywords

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