Striatal Dopamine Links Gastrointestinal Rerouting to Altered Sweet Appetite (2015)

Cell Metab. 2015 Nov 18. pii: S1550-4131(15)00525-2. doi: 10.1016/j.cmet.2015.10.009.

Han W1, Tellez LA2, Niu J3, Medina S4, Ferreira TL5, Zhang X6, Su J7, Tong J8, Schwartz GJ9, van den Pol A6, de Araujo IE10.


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.