title: Striatal Dopamine Links Gastrointestinal Rerouting to Altered Sweet Appetite.
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.
authors.affiliation: 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.
authors.forename: Wenfei
authors.initials: W
authors.lastname: Han
authors.affiliation: The John B. Pierce Laboratory, New Haven, CT 06519, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, USA.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Tellez
authors.affiliation: 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.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Niu
authors.affiliation: The John B. Pierce Laboratory, New Haven, CT 06519, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Medina
authors.affiliation: 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.
authors.forename: Tatiana L
authors.initials: TL
authors.lastname: Ferreira
authors.affiliation: Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06519, USA.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Laboratory of Oral Biomedical Science and Translational Medicine, School of Stomatology, Tongji University, Shanghai 200072, China.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Su
authors.affiliation: Division of Endocrinology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Jenny
authors.initials: J
authors.lastname: Tong
authors.affiliation: Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Schwartz
authors.affiliation: Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06519, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: van den Pol
authors.affiliation: 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.
authors.forename: Ivan E
authors.initials: IE
authors.lastname: de Araujo
mesh_terms: D000200:Action Potentials; D000818:Animals; D001069:Appetite Regulation; D019422:Dietary Sucrose / Q000008:administration & dosage / Q000378:metabolism; D004298:Dopamine / Q000502:physiology; D059290:Dopaminergic Neurons / Q000502:physiology*; D004386:Duodenum / Q000378:metabolism / Q000601:surgery; D002149:Energy Intake; D015390:Gastric Bypass; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism / Q000601:surgery; D008297:Male; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000166:cytology
chemical_list: D019422:Dietary Sucrose; D005947:Glucose; D004298:Dopamine