SGLT1 sugar transporter/sensor is required for post-oral glucose appetition

Abstract

Recent findings suggest that the intestinal sodium-glucose transporter 1 (SGLT1) glucose transporter and sensor mediates, in part, the appetite-stimulation actions of intragastric (IG) glucose and nonmetabolizable α-methyl-d-glucopyranoside (MDG) infusions in mice. Here, we investigated the role of SGLT1 in sugar conditioning using SGLT1 knockout (KO) and C57BL/6J wild-type (WT) mice. An initial experiment revealed that both KO and WT mice maintained on a very low-carbohydrate diet display normal preferences for saccharin, which was used in the flavored conditioned stimulus (CS) solutions. In experiment 2, mice were trained to drink one flavored solution (CS+) paired with an IG MDG infusion and a different flavored solution (CS-) paired with IG water infusion. In contrast to WT mice, KO mice decreased rather than increased the intake of the CS+ during training and failed to prefer the CS+ over the CS- in a choice test. In experiment 3, the KO mice also decreased their intake of a CS+ paired with IG glucose and avoided the CS+ in a choice test, unlike WT mice, which preferred the CS+ to CS-. In experiment 4, KO mice, like WT mice preferred a glucose + saccharin solution to a saccharin solution. These findings support the involvement of SGLT1 in post-oral glucose and MDG conditioning. The results also indicate that sugar malabsorption in KO mice has inhibitory effects on sugar intake but does not block their natural preference for sweet taste.

Gut-Brain Cross-Talk in Metabolic Control

“…In distinction to the feed-back mechanisms of satiation, the term “appetition” was coined for this feed-forward phenomenon (Sclafani, 2013). Using this paradigm, it was demonstrated that the sodium-glucose transporter-1 (SGLT1) is required for post-oral glucose (Sclafani et al, 2016), and the fatty acid sensors GPR40 and GPR120 for post-oral fat (Sclafani et al, 2013), to mediate the development of preferences for flavors associated with glucose or fats, respectively. Interestingly, in contrast to the satiating post-oral effects of carbohydrates and fats, neither vagal afferents nor sensory fibers in the splanchnic nerve are essential for these “appetition” effects (Sclafani et al, 2003).…”

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

“…However, the identity of the appetition signal generated by SGLT1 remains to be identified 113 . Moreover, studies in mice undergoing bariatric surgery suggest that sugar sensing in the duodenum plays a key role in mediating dorsal striatal dopamine release in response to sugar ingestion M A N U S C R I P T…”

MCH receptor deletion does not impair glucose-conditioned flavor preferences in mice

“…Once ingested, sugars also stimulate post-oral sensors that enhance the reward value of the nutrient in part by activating the brain dopamine system [6,27]. Recent findings indicate that intestinal sodium-glucose transporters (SGLTs), which also function as glucose sensors (“transceptors”), are critically involved in post-oral stimulation of sugar appetite, a process referred to as appetition [19,25,40]. Other evidence suggests that glucose sensors in the hepatic-portal region contribute to sugar reward [16].…”