Karen Ackroff

Role of gut nutrient sensing in stimulating appetite and conditioning food preferences

The discovery of taste and nutrient receptors (chemosensors) in the gut has led to intensive research on their functions. Whereas oral sugar, fat, and umami taste receptors stimulate nutrient appetite, these and other chemosensors in the gut have been linked to digestive, metabolic, and satiating effects that influence nutrient utilization and inhibit appetite. Gut chemosensors may have an additional function as well: to provide positive feedback signals that condition food preferences and stimulate appetite. The postoral stimulatory actions of nutrients are documented by flavor preference conditioning and appetite stimulation produced by gastric and intestinal infusions of carbohydrate, fat, and protein. Recent findings suggest an upper intestinal site of action, although postabsorptive nutrient actions may contribute to flavor preference learning. The gut chemosensors that generate nutrient conditioning signals remain to be identified; some have been excluded, including sweet (T1R3) and fatty acid (CD36) sensors. The gut-brain signaling pathways (neural, hormonal) are incompletely understood, although vagal afferents are implicated in glutamate conditioning but not carbohydrate or fat conditioning. Brain dopamine reward systems are involved in postoral carbohydrate and fat conditioning but less is known about the reward systems mediating protein/glutamate conditioning. Continued research on the postoral stimulatory actions of nutrients may enhance our understanding of human food preference learning.

Glucose- and fructose-conditioned flavor preferences in rats: taste versus postingestive conditioning.

Flavor preferences conditioned by glucose and fructose were compared using two training methods. With the simultaneous method preferences can be reinforced by the flavor and/or the postingestive consequences of nutrients, whereas with the delayed method preferences are reinforced only by postingestive nutritive effects. In Experiment 1, food-deprived rats displayed similar preferences for flavors (CS+) added to an 8% glucose or 8% fructose solution over flavors (CS-) added to a noncaloric saccharin solution (simultaneous conditioning). Other rats learned to prefer a CS+ flavor paired with the delayed (10 min) presentation of 8% glucose over a CS- flavor paired with delayed saccharin. Fructose failed to condition a flavor preference with the delayed paradigm. Taken together, these data suggest that the preference for a flavor mixed in a fructose solution is reinforced by the sweet taste, not the postingestive effects of the sugar. Experiment 2 tested this idea by devaluing the taste of the sugar solutions by quinine adulteration. Rats initially avoided both glucose-quinine and fructose-quinine solutions in favor of a saccharin solution. Following one-bottle training, they came to prefer the glucose-quinine but not the fructose-quinine solution over the saccharin solution. The glucose-trained rats also showed stronger preferences for sucrose-quinine solutions than did the fructose-trained rats. These findings, along with other recent data, indicate that fructose-conditioned preferences are based primarily on the sugars palatable taste. Glucose, in contrast, can condition strong preferences based on its taste as well as its postingestive actions.

Reinforcement value of sucrose measured by progressive ratio operant licking in the rat.

Progressive ratio (PR) schedules, which require increasing numbers of responses for successive reinforcements, are widely used to measure the reward value of foods, fluids, and drugs in operant lever-pressing tasks. The present study evaluated a PR operant licking task as a measure of sweet taste reward. In Experiment 1, food deprived rats were offered sucrose to drink on PR lick or fixed ratio (FR) lick schedules (30 min/day). In Experiment 2, nondeprived rats were offered sucrose to drink on PR or FR schedules and free access to water and food 23 h/day. In both experiments, the FR rats increased and then decreased their sucrose solution intake as concentration increased from 1% to 32% or 64%. The PR rats, in contrast, showed a near-linear increase in sucrose solution intake, lick rates, and break points (highest ratio completed) as a function of sucrose concentration. The PR rats drank less sucrose than did the FR rats although they emitted more total licks at the highest concentration tested. These results are similar to those reported with PR lever-pressing tasks. Thus, PR operant licking, which requires minimal training and equipment, is a useful alternate measure of fluid reward in rodents.

Fat appetite in rats: the response of infant and adult rats to nutritive and non-nutritive oil emulsions.

Fat appetite was studied in rats using corn oil and mineral oil emulsions. In Experiment 1 ingestive responses to intraoral infusions were measured in rat pups 6-15 days of age. By 12-15 days of age pups responded more to oil emulsions (10% and 30%) than they did to water or emulsifier solution. The corn and mineral oil emulsions were almost as effective as milk but less effective than sucrose (0.3M) in stimulating ingestion. Experiments 2 and 3 examined the acceptance and preference for oil emulsions in adult rats. The corn oil and mineral oil emulsions were equally acceptable to non-deprived rats, as measured by 3-min and 30-min one-bottle tests. Food deprivation increased the one-bottle intake of both emulsions. In two-bottle tests, rats displayed a slight corn oil preference when non-deprived, but developed a strong preference when food deprived. Taken together, the results suggest that rats have an unlearned attraction to the orosensory qualities of emulsified oils and they learn to prefer corn oil based on its postingestive nutritive effects.

Selective effects of vagal deafferentation and celiac–superior mesenteric ganglionectomy on the reinforcing and satiating action of intestinal nutrients

The role of vagal afferents and splanchnic fibers in nutrient-induced flavor conditioning and feeding suppression was determined. Male rats were fitted with intraduodenal (ID) catheters and given subdiaphragmatic vagal deafferentation (SDA), celiac-superior mesenteric ganglionectomy (CGX), combined (COM) treatments, or sham surgery. In separate conditioning trials, they were trained to drink (30 min/day) flavored saccharin solutions paired with concurrent ID infusions of 8% maltodextrin or water and 3.55% corn oil or water. Experiment 1 revealed that SDA and sham rats showed equal preferences for the nutrient-paired flavors over the water-paired flavors. In contrast, SDA rats, unlike sham rats, failed to suppress their intake of a palatable fluid when infused intraduodenally with maltodextrin or corn oil. Experiment 2 revealed that CGX, COM and sham rats all developed preferences for the maltodextrin-paired flavor, although CGX alone or COM attenuated the conditioned preference. CGX and COM treatments also attenuated or blocked the feeding inhibitory actions of ID nutrient infusions. These findings along with prior data indicate that gut vagal afferents and splanchnic nerves are not essential for flavor-nutrient preference conditioning, whereas both vagal afferents and splanchnic nerves are implicated in carbohydrate- and fat-induced satiation.

High-fat diet preference and overeating mediated by postingestive factors in rats

The role of postingestive factors in the preference for and overconsumption of high-fat (HF) foods, relative to high-carbohydrate (HC) foods, was investigated using a self-regulated intragastric feeding procedure. On one-bottle training days, rats drank one flavored saccharin solution [conditioned stimulus (CS) + HF] paired with intragastric infusions of an HF liquid diet, a second flavored solution (CS+HC) paired with an HC liquid diet, and a third flavored solution (CS-) paired with intragastric water. The diets had the same energy and protein content; the CS solutions and infusions along with chow were available ad libitum. The rats drank more CS and self-infused more diet on HF than HC training days. In two-bottle choice tests, the rats preferred the CS+HF to the CS+HC and both CS+HF and CS+HC to the CS-. The rats consumed more CS+HF than CS+HC by taking more bouts per day; bout sizes did not reliably differ. In a subsequent experiment, rats preferred the CS+HF even though diet intakes in training were matched. In a final experiment, the CS+HC and CS+HF intakes were equated in training by diluting the HC diet. Now the rats did not reliably prefer the CS+HF to the CS+HC, yet caloric intakes were much higher on CS+HF than CS+HC training days. Thus, relative to an isocaloric HC diet, the postingestive effects of HF diets stimulate overeating and condition a stronger flavor preference. Reduced satiety rather than increased reinforcement may be the direct promoter of overeating. However, postingestive reinforcement may enhance the selection of HF foods when a choice of HF and HC foods is available.

Flavor preferences conditioned by intragastric fructose and glucose: differences in reinforcement potency

Many prior conditioning studies indicate that fructose, unlike glucose, has minimal postingestive reinforcing effects. Using a new training procedure, food-restricted rats were trained in alternate 20-h/day sessions with one flavored solution (CS+F) paired with intragastric (IG) infusions of 16% fructose and another flavor (CS-) paired with IG water. In subsequent two-bottle tests they showed a robust (85%) preference for the CS+F over the CS-. A third flavor (CS+G) was then paired with IG 16% glucose, and it was strongly preferred to the CS+F. When retrained 30 min/day with new flavors paired with IG fructose, glucose, or water the rats learned only a CS+G preference. When training was extended to 20 h/day, a CS+F preference developed. New rats trained 20 h/day with two-bottle access to CS+F and CS- paired with IG fructose and water failed to acquire a CS+F preference. Other rats rapidly developed a strong preference when trained with concurrent access to CS+G and CS- paired with IG glucose and water. These data indicate that both fructose and glucose generate postingestive reinforcing signals, but that the fructose signals are weaker and/or delayed relative to those produced by glucose.

Post-oral infusion sites that support glucose-conditioned flavor preferences in rats.

Rats learn to prefer a flavored solution (CS+) paired with a gastrointestinal glucose infusion over an alternate flavor (CS-) paired with a non-caloric infusion. Prior work implicates a post-gastric site of glucose action, which is the focus of this study. In Exp. 1, male rats (8-10/group) were infused in the duodenum (ID), mid-jejunum (IJ), or distal ileum (II) with 8% glucose or water as they drank saccharin-sweetened CS+ and CS- solutions, respectively, in one-bottle 30-min sessions. Two-bottle tests (no infusions) were followed by a second train-test cycle. By the second test, the ID and IJ groups preferred the CS+ (69%, 67%) to the CS- but the II group did not (48%). Satiation tests showed that ID and IJ infusions of glucose reduced intake of a palatable solution similarly, while II infusions were ineffective. In Exp. 2, rats (10/group) drank CS solutions in one-bottle, 30-min sessions and were given 2-h ID or hepatic portal vein (HP) infusions. The CS+ and CS- were paired with 10 ml infusions of 10% glucose and 0.9% saline, respectively. Following 8 training sessions, the ID group preferred the CS+ (67%) to the CS- but the HP group did not (47%) in a two-bottle test. The similar CS+ preferences displayed by ID and IJ, but not II groups implicate the jejunum as a critical site for glucose-conditioned preferences. A pre-absorptive glucose action is indicated by the CS+ preference displayed by ID but not HP rats in Exp. 2. Our data were obtained with non-nutritive CS solutions. HP glucose infusions are reported to condition preferences for a flavored food that itself has pre- and post-absorptive actions. Thus, there may be multiple sites for glucose conditioning with the upper or mid-intestines being the first site of action.

Flavor preferences conditioned by sugars: Rats learn to prefer glucose over fructose

The reinforcing effects of glucose and fructose were compared using flavor preference conditioning paradigms. Female rats given access to flavored glucose and flavored fructose solutions developed preferences for the glucose- over the fructose-paired flavor, as well as for unflavored glucose over unflavored fructose. This effect was obtained with 8% and 32% solutions, and with nondeprived and deprived rats. In most cases, the glucose preference was not immediate but appeared only after the rats had one-bottle experience with the two sugars. Female rats also preferred a glucose-paired flavor over a flavor that was paired with a noncaloric saccharin solution. A similar but somewhat weaker preference was displayed for a fructose-paired flavor over a saccharin-paired flavor. Both male and female rats acquired preferences for flavored chow that was paired with the intake of a 32% glucose solution over flavored chow paired with 32% fructose intake. Together, these results indicate that glucose has more potent postingestive reinforcing effects than does fructose. This may explain why rats consume more glucose than fructose in one-bottle acceptance as well as two-bottle preference tests.

Flavor preferences conditioned by intragastric nutrient infusions in food restricted and free-feeding rats

The role of deprivation state in flavor preference conditioning by nutrients was investigated in rats fitted with intragastric (IG) catheters. In different experiments, food restricted (FR) and food ad libitum (AL) groups were trained to drink one flavored solution (CS+) paired with IG infusions of maltodextrin, corn oil, or casein and another flavored solution (CS-) paired with IG water infusions. Training intakes of the CS solutions were limited to equate the exposure of the FR and AL groups. The IG nutrient infusions conditioned flavor preferences in FR and AL groups which, in three of four experiments, were of similar magnitude. Food restriction did, however, increase the overall intake of the CS+ solutions during testing. Rats trained with one CS+ while food restricted and a second CS+ while food unrestricted showed similar preferences for the two CS+ flavors. Prefeeding AL rats to satiety with chow prior to daily training sessions did not prevent them from developing a preference for a CS+ paired with IG maltodextrin. These findings indicate that the postoral actions of nutrients are reinforcing in food sated as well as hungry rats.