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

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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
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Reprinted with permission from [8] and [71]

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From [217]

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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

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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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  1. Laboratory of Neurobiology of Appetite, Department of Pharmacology, CINVESTAV, 07360, Mexico City, Mexico

    Ranier Gutierrez & Esmeralda Fonseca

  2. Department of Neurobiology, Duke University Medical Center, Durham, NC, 27710, USA

    Sidney A. Simon

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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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