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 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 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.

Gut-Brain Cross-Talk in Metabolic Control

“…If confirmed, this logic may explain why, over the long term, energy content trumps taste when it comes to food choice. The same group of researchers demonstrated that surgically bypassing the duodenum and jejunum in mice abolished the dopamine-stimulating and appetite-enhancing effects of intragastric glucose (Han et al, 2016), suggesting this as a critical mechanism underlying the reduced sweet craving and carbohydrate intake after bariatric surgery in rodents (Shin and Berthoud, 2011; Tichansky et al, 2011; Wilson-Pérez et al, 2013b). …”

Sugar addiction: is it real? A narrative review

“…Postingestive glucose can activate the brain dopamine reward circuit independently of sweet taste,57 and that sweet appetite may even be stimulated by the presence of glucose in the gastrointestinal tract 58…”

DRD2: Bridging the Genome and Ingestive Behavior

“…Consequently, there are many pathways by which genetic variations that impact DA signaling can influence food intake and obesity. In addition, emerging work strongly suggests that adiposity, metabolic dysfunction and diets high in saturated fat and sugar produce adaptations in DA function at the molecular, cellular and circuit levels to impact DA-dependent functions ranging from working memory and compulsive behaviors [6–20] to food preference and nutrient sensing [21, 22] and regulation of glucose metabolism [23–26]. Thus DA genetic variants may influence intake not only by conferring initial risk but also by influencing brain adaptations [27, 28].…”