The Effects of Roux-en-Y Gastric Bypass on Glucose- vs. Fructose-Associated Conditioned Flavor Preference

Abstract

In rodents, repeated single-bottle exposures to distinctly flavored isocaloric glucose and fructose solutions, two sugars with different metabolic pathways, eventually lead to a preference for the former. Because Roux-en-Y gastric bypass (RYGB) surgery decreases preference for and intake of sugar solutions in rats, we tested whether RYGB would curtail the conditioning of a preference for a glucose-paired vs. fructose-paired flavor. RYGB (♂ n=11; ♀ n=10) and sham-operated (SHAM; ♂ n=9; ♀ n=10) rats were trained with a single bottle (30 min/day) containing 8% glucose solution flavored with either 0.05% grape or cherry Kool-Aid (Glu/CS^G) or 8% fructose solution with the alternative Kool-Aid flavor (Fru/CS^F) in an alternating fashion for 8 days. To determine baseline preferences, a 4-day 30-min two-bottle test was used to assess preference for Glu/CS^G vs. Fru/CS^F before training. After training, 2-day 30-min two-bottle tests assessed preference for the a) Glu/CS^G (CS^G-flavored 8% glucose solution) vs Fru/CS^F (CS^F-flavored 8% fructose solution), b) CS^G- vs. CS^F-flavored mixture of 4% glucose & 4% fructose (isocaloric), c) CS^G- vs. CS^F-flavored 0.2% saccharin ("sweet", no calories), and d) CS^G- vs. CS^F-flavored water. During training, only male SHAM rats demonstrated progressively increased intake of Glu/CS^G over Fru/CS^F, and female SHAM rats displayed a trend. RYGB eliminated any difference in single-bottle intake of these solutions during training, regardless of sex. Like their male and female SHAM counterparts, male RYGB rats displayed a conditioned preference for the CS^G-associated stimulus in Tests 1-3. Although female RYGB rats displayed acquisition of the conditioned flavor preference in Test 1, unlike the other groups, when the differential sugar cue between the two solutions was removed in Tests 2 and 3, female rats did not display a CS^G preference. When the sugar and sweetener cues were both removed on Test 4, all groups displayed some generalization decrement. Thus, RYGB does not compromise the ability of rats to learn and express a glucose- vs. fructose-associated conditioned flavor preference when the exact CS used in training is presented in testing. The mechanistic basis for the sex difference in the effect of RYGB on the generalization decrement observed in this type of flavor preference learning warrants further study.

Keywords: Roux-en-Y gastric bypass; conditioned flavor preference; fructose; generalization decrement; glucose; sex difference.

Figure 1

Schedule of experiments. A) Flow of experiment. B) Procedures of Pre-Test, Training, and Test. The solution(s) were presented for 30 min in a day. Food and water were removed from the home cage during the presentation and for the following 1 hour. Animals were assigned to be exposed to either of glucose-grape and fructose-cherry or glucose-cherry and fructose-grape in a balanced fashion. In both cases, the glucose and fructose solutions were defined as Glu/CS^G and Fru/CS^F respectively. Each stimulus was presented every other day on training. The stimulus order was counterbalanced in each group (RYGB and SHAM).

Figure 2

Mean ± SE body weight changes after RYGB or sham operation for males and females. The weight on each day was presented as percentage of that on a day before surgery (baseline). The mean initial starting weight ± se on the baseline was 291.8 ± 5.53 g in Female-RYGB (n = 10), 296.3 ± 8.03 g in Female-SHAM (n = 10), 527.64 ± 7.17 g in Male-RYGB (n = 11), and 517.56 ± 14.66 g in Male-SHAM (n = 9).

Figure 3

Mean (bars) and individual (symbols) CS^G-flavored solution preference scores on the last two days of the two-bottle Pre-Test (A) and the various two-bottle tests after training (C), and intake volume during single bottle Training (B); * in panels A and C represents significant (p ≤ 0.05) increases from 50%; ‡ in panel C represents significant (p ≤ 0.05) difference from Glu/CS^G preference during Pre-Test. # represents significant (p ≤ 0.05) difference between Glu/CS^G and Fru/CS^F intake on a given test trial in the series in panel B.