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Front. Integr. Neurosci. | doi: 10.3389/fnint.2018.00057

Sugar Metabolism Regulates Flavor Preferences and Portal Glucose Sensing

Linli Zhang1, 2, 3, 4, Wenfei Han2, 5, 6, Chenguanlu Lin2, 7, Fei Li3, 4 and  Ivan E. De Araujo2, 5, 6, 8*
  • 1Shanghai Children's Medical Center, China
  • 2John B. Pierce Laboratory, United States
  • 3Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, China
  • 4Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, China
  • 5Department of Psychiatry, Yale School of Medicine, Yale University, United States
  • 6Icahn School of Medicine at Mount Sinai, United States
  • 7The Affiliated Stomatology Hospital, Tongji University, China
  • 8Department of Cellular and Molecular Physiology, Yale University School of Medicine, United States

In most species, including humans, food preference is primarily controlled by nutrient value. In particular, glucose-containing sugars exert exquisitely strong effects on food choice via gut-generated signals. However, the identity of the visceral signals underlying glucose’s rewarding effects remains uncertain. In particular, it is unknown whether sugar metabolism mediates the formation of preferences for glucose-containing sugars. Using the mouse as a model organism, we made use of a combination of conditioning schedules, gastrointestinal nutrient administration, and chromatographic/electrochemical methods to assess the behavioral and neural effects of activating the gut with either metabolizable glucose or a non-metabolizable glucose analogue. We show that mice display much superior preferences for flavors associated with intra-gastric infusions of glucose compared to flavors associated with intra-gastric infusions of the non-metabolizable glucose analogue α-methyl-D-glucopyranoside (“MDG”, an activator of intestinal sodium/glucose cotransporters). These effects were unaffected by surgical bypassing of the duodenum, suggesting glucose-specific post-absorptive sensing mechanisms. Consistently, intra-portal infusions of glucose, but not of MDG, induced significant rises in dopamine levels within brain reward circuits. Our data reveal that the unmatched rewarding effects of glucose-containing sugars cannot be accounted for by metabolism-independent activation of sodium/glucose cotransporters; rather, they point to glucose metabolism as the physiological mechanism underlying the potent reward value of sugar-sweetened flavored beverages. In particular, no circulating “gut factors” need to be invoked to explain the reward value of ingested glucose. Instead, they suggest that portal-mesenteric sensing of metabolizable glucose as the preferential physiological pathway for sugar reward.

Keywords: flavor preferences, dorsal striatum, Dopamine, glucose metabolism, sugar

Received: 04 Sep 2018; Accepted: 06 Nov 2018.

Edited by:

Ranier Gutierrez, Centro de Investigación y de Estudios Avanzados (CINVESTAV), Mexico

Reviewed by:

Henry H. Yin, Duke University, United States
Gustavo Pacheco-Lopez, Universidad Autónoma Metropolitana, Mexico  

Copyright: © 2018 Zhang, Han, Lin, Li and De Araujo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Ivan E. De Araujo, Icahn School of Medicine at Mount Sinai, New York, 10029, New York, United States,