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Cell Metab. 2016 Jan 12;23(1):103-12. doi: 10.1016/j.cmet.2015.10.009. Epub 2015 Nov 19.

Striatal Dopamine Links Gastrointestinal Rerouting to Altered Sweet Appetite.

Author information

1
Laboratory of Oral Biomedical Science and Translational Medicine, School of Stomatology, Tongji University, Shanghai 200072, China; The John B. Pierce Laboratory, New Haven, CT 06519, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, USA.
2
The John B. Pierce Laboratory, New Haven, CT 06519, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, USA.
3
The John B. Pierce Laboratory, New Haven, CT 06519, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, USA; Division of Endocrinology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
4
The John B. Pierce Laboratory, New Haven, CT 06519, USA.
5
The John B. Pierce Laboratory, New Haven, CT 06519, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, USA; Mathematics, Computing and Cognition Center, Federal University of ABC, Santo André 09210, Brazil.
6
Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06519, USA.
7
Laboratory of Oral Biomedical Science and Translational Medicine, School of Stomatology, Tongji University, Shanghai 200072, China.
8
Division of Endocrinology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
9
Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA.
10
The John B. Pierce Laboratory, New Haven, CT 06519, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, USA; Department of Physiology, Yale University School of Arts and Sciences, New Haven, CT 06511, USA. Electronic address: iaraujo@jbpierce.org.

Abstract

Reductions in calorie intake contribute significantly to the positive outcome of bariatric surgeries. However, the physiological mechanisms linking the rerouting of the gastrointestinal tract to reductions in sugar cravings remain uncertain. We show that a duodenal-jejunal bypass (DJB) intervention inhibits maladaptive sweet appetite by acting on dopamine-responsive striatal circuitries. DJB disrupted the ability of recurrent sugar exposure to promote sweet appetite in sated animals, thereby revealing a link between recurrent duodenal sugar influx and maladaptive sweet intake. Unlike ingestion of a low-calorie sweetener, ingestion of sugar was associated with significant dopamine effluxes in the dorsal striatum, with glucose infusions into the duodenum inducing greater striatal dopamine release than equivalent jejunal infusions. Consistently, optogenetic activation of dopamine-excitable cells of the dorsal striatum was sufficient to restore maladaptive sweet appetite in sated DJB mice. Our findings point to a causal link between striatal dopamine signaling and the outcomes of bariatric interventions.

PMID:
26698915
PMCID:
PMC4715689
DOI:
10.1016/j.cmet.2015.10.009
[Indexed for MEDLINE]
Free PMC Article

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