Zukerman S, Glendinning JI, Margolskee RF, Sclafani A. T1R3 taste receptor is critical for sucrose but not Polycose taste. In addition to their well-known preference for sugars, mice and rats avidly consume starch-derived glucose polymers (e.g., Polycose). T1R3 is a component of the mammalian sweet taste receptor that mediates the preference for sugars and artificial sweeteners in mammals. We examined the role of the T1R3 receptor in the ingestive response of mice to Polycose and sucrose. In 60-s two-bottle tests, knockout (KO) mice preferred Polycose solutions (4 -32%) to water, although their overall preference was lower than WT mice (82% vs. 94%). KO mice also preferred Polycose (0.5-32%) in 24-h two-bottle tests, although less so than WT mice at dilute concentrations (0.5-4%). In contrast, KO mice failed to prefer sucrose to water in 60-s tests. In 24-h tests, KO mice were indifferent to 0.5-8% sucrose, but preferred 16 -32% sucrose; this latter result may reflect the post-oral effects of sucrose. Overall sucrose preference and intake were substantially less in KO mice than WT mice. However, when retested with 0.5-32% sucrose solutions, the KO mice preferred all sucrose concentrations, although they drank less sugar than WT mice. The experience-induced sucrose preference is attributed to a post-oral conditioned preference for the T1R3-independent orosensory features of the sugar solutions (odor, texture, T1R2-mediated taste). Chorda tympani nerve recordings revealed virtually no response to sucrose in KO mice, but a near-normal response to Polycose. These results indicate that the T1R3 receptor plays a critical role in the tastemediated response to sucrose but not Polycose.preference; C57BL/6J mice; chorda tympani nerve; saccharin; postoral conditioning THE TASTE OF SUGAR IS HIGHLY attractive to humans and many other animal species. Studies of inbred mouse strains led to the identification of the T1R2 and T1R3 receptor proteins that dimerize to form a sweet taste receptor (1). Selective elimination of these receptor proteins in knockout mice attenuates or completely blocks the behavioral and gustatory nerve responses to sugars and artificial sweeteners (7, 40). Further, allelic variation in the Tas1r3 gene, which codes for the T1R3 protein (3,(17)(18)(19)24), contributes to strain differences in sensitivity (9), lick responsiveness (8, 10), peripheral taste nerve responsiveness (11), and daily intake and preference (11, 22) for sugars and artificial sweeteners.Sugars are not the only carbohydrates that have an attractive taste to some nonhuman species. Twenty years ago, our laboratory published a series of papers demonstrating that rats, mice, hamsters, and gerbils are strongly attracted to the taste of starch-derived glucose polymers such as Polycose and other maltodextrins (26). Behavioral and electrophysiological evidence indicates that Polycose and sucrose have qualitatively distinct taste sensations in rodents. For example, aversions conditioned to Polycose or sucrose do not cross-generalize, and some ta...

Zukerman S, Ackroff K, Sclafani A. Post-oral appetite stimulation by sugars and nonmetabolizable sugar analogs. Am J Physiol Regul Integr Comp Physiol 305: R840 -R853, 2013. First published August 7, 2013 doi:10.1152/ajpregu.00297.2013.-Post-oral sugar actions enhance the intake of and preference for sugar-rich foods, a process referred to as appetition. Here, we investigated the role of intestinal sodium glucose cotransporters (SGLTs) in sugar appetition in C57BL/6J mice using sugars and nonmetabolizable sugar analogs that differ in their affinity for SGLT1 and SGLT3. In experiments 1 and 2, food-restricted mice were trained (1 h/day) to consume a flavored saccharin solution [conditioned stimulus (CSϪ)] paired with intragastric (IG) self-infusions of water and a different flavored solution (CSϩ) paired with infusions of 8 or 12% sugars (glucose, fructose, and galactose) or sugar analogs (␣-methyl-D-glucopyranoside, MDG; 3-O-methyl-D-glucopyranoside, OMG). Subsequent twobottle CSϩ vs. CSϪ choice tests were conducted without coinfusions. Infusions of the SGLT1 ligands glucose, galactose, MDG, and OMG stimulated CSϩ licking above CSϪ levels. However, only glucose, MDG, and galactose conditioned significant CSϩ preferences, with the SGLT3 ligands (glucose, MDG) producing the strongest preferences. Fructose, which is not a ligand for SGLTs, failed to stimulate CSϩ intake or preference. Experiment 3 revealed that IG infusion of MDGϩphloridzin (an SGLT1/3 antagonist) blocked MDG appetition, whereas phloridzin had minimal effects on glucose-induced appetition. However, adding phloretin (a GLUT2 antagonist) to the glucoseϩphloridzin infusion blocked glucose appetition. Taken together, these findings suggest that humoral signals generated by intestinal SGLT1 and SGLT3, and to a lesser degree, GLUT2, mediate post-oral sugar appetition in mice. The MDG results indicate that sugar metabolism is not essential for the post-oral intake-stimulating and preference-conditioning actions of sugars in mice.post-oral sugar conditioning; glucose; fructose; galactose FOOD INTAKE AND PREFERENCE are guided by oral sensations (taste, odor, and mouth feel) that contribute to the identification and hedonic evaluation of food flavor. Considerable progress has been made in identifying the taste receptors that respond to sugar, fat, and amino acids that provide attractive sweet, fatty, and umami flavors to foods (8). The appetite for such foods is further enhanced by the post-oral actions of ingested nutrients (50). This is demonstrated in laboratory rodents by the intake stimulation and learned preferences for arbitrary flavors (conditioned stimuli, CS) that are paired with gastric or intestinal infusions of sugar, fat, and proteins (or glutamate) (50). However, relatively little is known about the sites and identities of the sensors that mediate the post-oral appetite-stimulating actions of nutrients, a process we refer to as appetition (48). In the case of sugars, several findings implicate the upper small intestine as a primary site of a...

-Although widely assumed to have only satiating actions, nutrients in the gut can also condition increases in intake in some cases. Here we studied the time course of post-oral nutrient stimulation of ingestion in food-restricted C57BL/6J mice. In experiment 1, mice adapted to drink a 0.8% sucralose solution 1 h/day, rapidly increased their rate of licking (within 4 -6 min) when first tested with an 8% glucose solution and even more so in tests 2 and 3. Other mice decreased their licking rate when switched from sucralose to 8% fructose, a sugar that is sweet like glucose but lacks positive post-oral effects in mice. The glucose-stimulated drinking is due to the sugar's post-oral rather than taste properties, because sucralose is highly preferred to glucose and fructose in brief choice tests. A second experiment showed that the glucose-stimulated ingestion is associated with a conditioned flavor preference in both intact and capsaicin-treated mice. This indicates that the post-oral stimulatory action of glucose is not mediated by capsaicin-sensitive visceral afferents. In experiment 3, mice consumed flavored saccharin solutions as they self-infused water or glucose via an intragastric (IG) catheter. The glucose self-infusion stimulated ingestion within 13-15 min in test 1 and produced a conditioned increase in licking that was apparent in the initial minute of tests 2 and 3. Experiment 4 revealed that IG self-infusions of a fat emulsion also resulted in post-oral stimulation of licking in test 1 and conditioned increases in tests 2 and 3. These findings indicate that glucose and fat can generate stimulatory post-oral signals early in a feeding session that increase ongoing ingestion and condition increases in flavor acceptance and preference revealed in subsequent feeding sessions. The test procedures developed here can be used to investigate the peripheral and central processes involved in stimulation of intake by post-oral nutrients.conditioned flavor acceptance and preference; fructose; sucralose; capsaicin deafferentation; intragastric infusion THE OROSENSORY AND POST-ORAL nutritional properties of foods are important determinants of food intake and preference. The flavors of palatable foods, i.e., their taste, odor, and texture, stimulate feeding, whereas post-oral signals are often assumed to have only inhibitory action via satiation signals that terminate a feeding bout and satiety signals that suppress postmeal eating (10,24,56). However, there is extensive evidence that nutrients can have other post-oral effects that condition food preferences and, in some cases, increase intake (42). This has been demonstrated, for example, by studies in which rodents are trained to drink a flavored nonnutritive solution paired with intragastric (IG) self-infusion of a nutrient. Typically, animals are given multiple training trials with one flavor (the conditioned stimulus or CSϩ) paired with a concurrent IG nutrient self-infusion and a second flavor (CSϪ) paired with IG water self-infusion on alternate training days. T...