Post-oral appetite stimulation by sugars and nonmetabolizable sugar analogs.
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 (CS-)] paired with intragastric (IG) self-infusions of water and a different flavored solution (CS+) paired with infusions of 8 or 12% sugars (glucose, fructose, and galactose) or sugar analogs (α-methyl-D-glucopyranoside, MDG; 3-O-methyl-D-glucopyranoside, OMG). Subsequent two-bottle CS+ vs. CS- choice tests were conducted without coinfusions. Infusions of the SGLT1 ligands glucose, galactose, MDG, and OMG stimulated CS+ licking above CS- levels. However, only glucose, MDG, and galactose conditioned significant CS+ preferences, with the SGLT3 ligands (glucose, MDG) producing the strongest preferences. Fructose, which is not a ligand for SGLTs, failed to stimulate CS+ intake or preference. Experiment 3 revealed that IG infusion of MDG+phloridzin (an SGLT1/3 antagonist) blocked MDG appetition, whereas phloridzin had minimal effects on glucose-induced appetition. However, adding phloretin (a GLUT2 antagonist) to the glucose+phloridzin 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.
Department of Psychology, Brooklyn College, City University of New York, Brooklyn, New York; and Cognition, Brain, and Behavior Doctoral Subprogram, Graduate School, City University of New York, New York, New York.
Steven
S
Zukerman
Karen
K
Ackroff
Anthony
A
Sclafani
D000284:Administration, Oral; D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects*; D002241:Carbohydrates / Q000008:administration & dosage*; D003213:Conditioning, Psychological / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D005518:Food Preferences / Q000187:drug effects*; D005632:Fructose / Q000008:administration & dosage / Q000378:metabolism; D005690:Galactose / Q000008:administration & dosage / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000187:drug effects / Q000378:metabolism; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008024:Ligands; D008297:Male; D008757:Methylglucosides / Q000008:administration & dosage / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012439:Saccharin / Q000008:administration & dosage; D012646:Self Administration; D051247:Sodium-Glucose Transport Proteins / Q000187:drug effects / Q000378:metabolism; D051269:Sodium-Glucose Transporter 1 / Q000187:drug effects / Q000378:metabolism; D013549:Sweetening Agents / Q000008:administration & dosage; D013997:Time Factors
D002241:Carbohydrates; D051273:Glucose Transporter Type 2; D008024:Ligands; D008757:Methylglucosides; C495682:Slc2a2 protein, mouse; C495675:Slc5a1 protein, mouse; C490297:Slc5a4b protein, mouse; D051247:Sodium-Glucose Transport Proteins; D051269:Sodium-Glucose Transporter 1; D013549:Sweetening Agents; D005632:Fructose; C027020:methylglucoside; D012439:Saccharin; D005947:Glucose; D005690:Galactose
fructose; galactose; glucose; post-oral sugar conditioning