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The neural basis of sugar preference

Abstract

When it comes to food, one tempting substance is sugar. Although sweetness is detected by the tongue, the desire to consume sugar arises from the gut. Even when sweet taste is impaired, animals can distinguish sugars from non-nutritive sweeteners guided by sensory cues arising from the gut epithelium. Here, we review the molecular receptors, cells, circuits and behavioural consequences associated with sugar sensing in the gut. Recent work demonstrates that some duodenal cells, termed neuropod cells, can detect glucose using sodium–glucose co-transporter 1 and release glutamate onto vagal afferent neurons. Based on these and other data, we propose a model in which specific populations of vagal neurons relay these sensory cues to distinct sets of neurons in the brain, including neurons in the caudal nucleus of the solitary tract, dopaminergic reward circuits in the basal ganglia and homeostatic feeding circuits in the hypothalamus, that alter current and future sugar consumption. This emerging model highlights the critical role of the gut in sensing the chemical properties of ingested nutrients to guide appetitive decisions.

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Fig. 1: Mechanisms of sensing glucose in gut epithelial cells.
Fig. 2: Heterogeneity within nodose neurons.
Fig. 3: Dopaminergic circuits in sugar sensing.
Fig. 4: A model of neuroepithelial circuits for sugar sensing.

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Acknowledgements

The authors thank S. Simon, R. Gutierrez, I. de Araujo and A. Sclafani for their early review of the manuscript. They also thank E. Bohórquez, M. Kaelberer, L. Rupprecht and P. Weng for their helpful edits.

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Glossary

Artificial sweeteners

Chemicals produced to mimic sugar by binding to the sweet taste receptor while also not being capable of being absorbed.

Exteroceptive

Sensitivity to stimuli originating outside the epithelial barrier of the body.

Interoceptive

Sensitivity to stimuli originating inside the epithelial barrier of the body.

Satiation

A process that suppresses nutrient intake and stops current consumption.

Satiety

A sense of fullness that persists after eating that suppresses future consumption.

Reinforcement

A procedure that results in the frequency or probability of a response being increased in such a way.

Appetition

A process that promotes nutrient intake.

Operant

A response that produces a consequential effect on the environment.

Flavour–nutrient conditioning

A form of classical conditioning where flavours of a solution are paired to infusions of chemical stimuli into the gut.

Sweet

The perception of taste associated with sugar, typically triggered by activation of sweet taste receptors in the tongue.

Enteroendocrine cells

Sensory epithelial cells of the gut that release hormones in response to various stimuli.

Neuropod cells

Sensory epithelial cells of the gut that synapse with nerves.

Nodose ganglion

The sensory ganglion of the vagus nerve located in the jugular foramen.

Bouts

Instances of food consumption.

Palatability

The degree of pleasantness or reward associated with stimulating the oral palate.

Mesolimbic system

A network of dopaminergic neurons consisting of the ventral striatum that receives input from the ventral tegmental area and is related to emotion and reward.

Nigrostriatal system

A network of dopaminergic neurons consisting of the dorsal striatum that receives input from the substantia nigra pars compacta and is linked to action initiation.

Hedonic

A degree of pleasantness or reward induced by an interaction or thought.

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Liu, W.W., Bohórquez, D.V. The neural basis of sugar preference. Nat Rev Neurosci 23, 584–595 (2022). https://doi.org/10.1038/s41583-022-00613-5

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