Striatal Dopamine Links Gastrointestinal Rerouting to Altered Sweet Appetite

Wenfei Han, Luis A. Tellez, Jingjing Niu, Sara Medina, Tatiana L. Ferreira, Xiaobing Zhang, Jiansheng Su, Jenny Tong, Gary J. Schwartz, Anthony Van Den Pol, Ivan E. De Araujo

Research output: Contribution to journalArticle

36 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)103-112
Number of pages10
JournalCell metabolism
Volume23
Issue number1
DOIs
StatePublished - Jan 12 2016

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Han, W., Tellez, L. A., Niu, J., Medina, S., Ferreira, T. L., Zhang, X., Su, J., Tong, J., Schwartz, G. J., Van Den Pol, A., & De Araujo, I. E. (2016). Striatal Dopamine Links Gastrointestinal Rerouting to Altered Sweet Appetite. Cell metabolism, 23(1), 103-112. https://doi.org/10.1016/j.cmet.2015.10.009