Glucose and Fat are Nutrients affecting food Preferences
Date: February 7, 2008
Speaker’s Name, Affiliation: Karen Ackroff Brooklyn College
Seminar Title: “Learned Flavor Preferences: The Variable Potency of Post-oral Nutrient Reinforcers”
Food reinforcement has two sources. The first is oral: the flavor (taste, odor, texture) of foods is a source of information for humans and animals finding and selecting among foods. There are unlearned preferences for certain taste qualities (e.g., sweet is preferred, bitter unpreferred) that influence their initial acceptability. Oral contact with food flavors is followed by post-oral effects of the nutrients, the second source of reinforcement. Both sources contribute to flavor preference learning when their effects are integrated by feeding-related brain circuits.
Post-oral effects of nutrients can modify the evaluation of food flavors, and our work has shown that nutrients vary in their ability to reinforce these learned flavor preferences.
Because the unconditioned responses to nutrient flavors complicates the analysis of their post-oral effects, we have used an intragastric flavor-nutrient learning procedure that eliminates orosensory contact with the nutrient (Ackroff & Sclafani, 1999).
As an animal consumes an arbitrary cue flavor (the conditioned stimulus, CS+, e.g., grape), it is infused intragastrically with a nutrient solution (the unconditioned stimulus, US). In alternate sessions it consumes a different cue flavor (CS-, e.g., cherry) paired with intragastric water infusion. Preference tests are conducted with the CS+ vs. the CS-. This procedure has several advantages. The animal controls the infusion, because its licks at the sipper tube are detected by a computer that operates a pump to infuse a matched amount of fluid. This simulates normal ingestion and prevents excessive infusion; it also halves the effective nutrient concentration in the stomach.
The accompanying flavor permits cephalic responses that should normalize gut handling of the nutrient. We have used two basic procedures with this automated infusion system. For long sessions, the animal is housed in the infusion apparatus, usually with ad libitum access to chow. In long sessions the animal drinks the cue flavors in multiple bouts and thus gets many paired exposures to the infusates.
For short sessions, the animal is housed elsewhere and placed in the cage for daily short sessions, which is advantageous for studying short-duration effects (e.g., preloads, drugs). For short sessions the rats are usually maintained on restricted rations to motivate session intake, though we have shown that this is not necessary for flavor preference learning (Yiin, Ackroff, & Sclafani, 2005a, 2005b).
The idea that post-oral reinforcing effects of nutrients are adequately summarized as flavor-calorie learning should be rejected.
Glucose and glucose polymers condition strong preferences with unpreferred flavors and in short session procedures, situations that produce poor learning with other nutrients. The three nutrients considered here are all weaker, but can be rescued by sweetening the cue flavors and by other methods that presumably increase the associability of flavor and nutrient.
Fructose, despite its presence in the reinforcing disaccharide sucrose, is quite poor at reinforcing flavor preferences on its own, requiring long sessions enhanced by food restriction.
Fat, in the form of corn oil emulsion, can condition flavor preferences as strong as those for glucose when measured against a CS- flavor, but in direct comparisons glucose-paired flavors are generally preferred. However, the study of mixed-nutrient diets demonstrated that at high concentrations, the satiating effects of an energy-dense high-carbohydrate diet can counteract its reinforcing effects so that the flavor paired with an isocaloric high-fat diet is preferred.
Ethanol‘s weak reinforcing effect relative to glucose requires intense flavors when used in short sessions. In direct comparisons, flavors associated with other nutrients are preferred to an ethanol-paired flavor.
Some general principles that contribute to reinforcing potency of nutrients are delayed post-oral effects, stimulus strength, and context. The post-absorptive effects of fructose and fat are delayed relative to those of glucose, which may account in part for their weaker effects.
They also follow different metabolic paths, which could delay the reinforcing event; even the source of glucose reinforcement is not clear, though it may involve intestinal detection (Drucker & Sclafani, 1997; Yiin, 2006). Stimulus strength effects are apparent in the need for enhanced flavor quality and moderation of nutrient concentration. Sweet taste may exert its effects by making the flavor more salient and thus more memorable, which could help its association with a delayed nutrient effect.
Sweet taste could also enhance cephalic responses and thus improve the handling of post-oral nutrients. Finally, sweet taste boosts the intake of the cue flavors and therefore increases the exposure to their paired infusions. Nutrient concentration should ideally be moderate: more concentrated carbohydrate counteracted reinforcement, and more concentrated ethanol is aversive.
Finally, the potency of a nutrient may depend on the overall nutrient context: training an animal with two nutrient-paired flavors can lead to different preference strengths for these flavors than when only one CS+ flavor is used (e.g., ethanol preferences are weaker when other nutrient-paired flavors are included). It is surprising that the weaker nutrients discussed here are not as reinforcing as glucose, given their presumed powerful effects on food and fluid intakes. More work that focuses on this disparity could lead to techniques for modulating the often excessive human attraction to these foods.
Discussion: (due to scheduling problems, the first 5 minutes of questions were not recorded)
Q. I am surprised that you could get animals to drink ethanol at all.
A. Yes, 5% ethanol solution is within the range that the animals would spontaneously drink.
Q. How long does it take before extinction in this experiment (referring to work done by Sclafani & Nissenbaum, 1988)?
A. A long, long time. We’ve tested up to 40 days, and still not gotten extinction of this effect.
Q. What was the CS- in this experiment?
A. We typically use cherry & grape flavored kool-aids. The CS- was just the kool-aid flavor not matched with glucose.
Q. (In reference to Sclafani et al, 1993) Can we rule out the possibility that fructose is causing an osmotic effect?
A. No, we can’t completely rule that out.
Q. Is fructose absorbed as rapidly as glucose?
A. No, it tends to be removed from the intestine at a slower rate than glucose, and once it is removed, it goes into a different metabolic pathway.
Q. How soon do they get chow after being fed fructose?
A. Approximately 1 hour later.
Q. What if you waited longer?
A. We have never tried that. (Comment: Dr. Sclafani thinks that the effects are pre-absorptive in the intestine, and thus waiting longer would not matter).
Q. Fructose does not release insulin, thus the calories are not being absorbed (in reference to the question above).
A. We’ve studied animals without insulin, and they still end up preferring glucose to fructose.
Q. Have you looked at ghrelin and sweet taste receptors in the stomach to see what is happening?
A. (Tony Sclafani): No, but we do not think that ghrelin is playing a role because we condition preferences both when animals are fed and fasted (in different states of hunger).
Q. Have you looked at 2-DG or some substitute to cause glucose to not enter the transport system? Will animals still prefer glucose?
A. (Tony Sclafani): The problem is that the malabsorption causes digestive problems which can result in nausea and an aversion.
Q. Would results be different if you could train animals to drink large amounts of alcohol over time?
A. They might be. Once they are conditioned to these preferences, then you can increase the concentration of the alcohol slowly over time.
Q. Did you say that you tried to use saccharin as an unconditioned stimulus?
A. We’ve tried it, but it didn’t work. Sucralose did work, so we think that sucralose may block the positive feedback system.
Q. I hear two potential hypotheses for these effects, one being that there is a special glucose specific receptor in the intestine.
A. That is the best simple explanation that we are seeing at this point.
Q. What was wrong with the theory that the more satiating the stimulus is, the easier it is to condition.
A. But if you make glucose too satiating, it will counteract this effect, so empirical findings do not support it.
Q. Didn’t you do some experiments with sham feeding?
A. We gave polycose by real and sham fed methods. It was preferred when it was “real fed” but in concentrated forms, they actually preferred it when it was matched with no calories.
Q. It seems that one problem is that you are relying on the amount of time, and this is a confounding effect. I’m wondering if you did some tests on motivation, would you be able to truly look at the reinforcing stimulus?
A. Not all tests were matched with concurrent infusions.
Q. Have you tried to block these responses with naloxone?
A. Yes, but it does not work?
Q. If you could control for caloric density, do you think animals would prefer corn oil or sucrose?
A. In the rat, sucrose is always preferred to corn oil.