Kevin P. Myers

Flavor-nutrient learning (FNL) refers to learning associations between a food’s flavor and the rewarding appetition signals that arise from post-oral nutrient sensing during or after a meal. In rodent models FNL reliably produces strong flavor preferences and increased intake of nutrient-paired flavors, implicating FNL as a presumptive obesogenic influence in the modern environment. However, evidence that FNL plays a causal role in diet-induced obesity is ambiguous. We have previously shown that degree of weight gain on a high-fat/sugar diet is associated with stronger FNL responses, but direction of causation was unclear. This paper reports three experiments investigating whether individual differences in FNL ‘conditionability’ are linked to obesity proneness prior to obesity onset. Two experiments comparing selectively-bred obesity-prone vs resistant strains found no strain differences in FNL. A third study in lean, outbred rats evaluated whether baseline individual differences in FNL prospectively predict weight gain on a cafeteria diet. Unexpectedly, rats who showed the strongest learned increase in intake of a nutrient-paired flavor subsequently gained the least weight when switched to cafeteria diet, suggesting FNL protects against weight gain. In fact, individual differences in FNL explained a portion of variance in cafeteria weight gain over and above measured kcal intake, implying a function for FNL in adaptively modulating metabolic responses to energy intake. Collectively, several studies have now shown individual differences in obesity proneness to be either positively correlated, uncorrelated, or negatively correlated with FNL, calling for a more nuanced view of how appetition influences intake and energy balance.

The simple sugars glucose and fructose share a common “sweet” taste quality mediated by the T1R2+T1R3 taste receptor. However, when given the opportunity to consume each sugar, rats learn to affectively discriminate between glucose and fructose on the basis of cephalic chemosensory cues. It has been proposed that glucose has a unique sensory property that becomes more hedonically positive through learning about the relatively more rewarding post-ingestive effects that are associated with glucose as compared to fructose. We tested this theory using intragastric (IG) infusions to manipulate the post-ingestive consequences of glucose and fructose consumption. Food-deprived rats with IG catheters repeatedly consumed multiple concentrations of glucose and fructose in separate sessions. For rats in the “Matched” group, each sugar was accompanied by IG infusion of the same sugar. For the “Mismatched” group, glucose consumption was accompanied by IG fructose, and vice versa. This condition gave rats orosensory experience with each sugar but precluded the differential post-ingestive consequences. Following training, avidity for each sugar was assessed in brief access and licking microstructure tests. The Matched group displayed more positive evaluation of glucose relative to fructose than the Mismatched group. A second experiment used a different concentration range and compared responses of the Matched and Mismatched groups to a control group kept naïve to the orosensory properties of sugar. Consistent with results from the first experiment, the Matched group, but not the Mismatched or Control group, displayed elevated licking responses to glucose. These experiments yield additional evidence that glucose and fructose have discriminable sensory properties and directly demonstrate that their different post-ingestive effects are responsible for the experience-dependent changes in the motivation for glucose versus fructose.