Obese rats with deficient leptin signaling exhibit heightened sensitivity to olfactory food cues

Abstract

The Zucker rat is used as a model of genetic obesity, and while Zucker rats have been well studied for their reduced sensitivity to leptin signaling and subsequent weight gain, little work has examined their responses to environmental signals that are associated with "hedonic" feeding. This study evaluated the effects of a high-fat food olfactory cue (bacon) in stimulating nose-poke food-seeking behavior on first exposure (novel) and after a period of access for consumption (familiar) in lean and obese Zucker rats at either 4 or 12 months of age, and under ad-lib fed (unrestricted; U) or chronically food-restricted (70% of ad-lib; R) conditions. Baseline nose-poke levels were comparable amongst all groups. At 4 months of age, only ObU rats displayed increased behavioral activation to familiar food cues. Twelve-month-old Ob rats, regardless of diet, exhibited substantially greater food-seeking behavior when exposed to both the novel and familiar olfactory cues. A strong positive correlation between body weight and nose-poke entries for the familiar food cue was observed at both ages, while this correlation for the novel food cue was significant in 12-month-old rats only. Similarly, there were strong positive correlations between food intake and poke entries for the familiar food cue was observed at both ages, while this correlation for the novel food cue was significant in 12-month-old rats only. Although it is possible that differences in olfactory sensitivity contribute to these behavioral effects, our findings support the interactions between food intake, obesity, and food-seeking behavior and are consistent with leptin inhibiting the brain's reactivity to food cues and suggest that the enhanced sensitivity to the food cues with leptin deficiency is likely to contribute to overeating and weight gain.

Figure 1

Timeline of experimental procedure. Baseline (B; day 1): rats placed in nose-poke arena to record baseline nose-poke activity. Novel food stimulation (N; day 2): rats exposed to olfactory stimulus (bacon) in nose-poke arena, nose-poke behavior measured. Conditioning (days 3–6): rats received bacon in their home cage, available for consumption. Familiar food stimulation (F; day 8): rats exposed to conditioned olfactory stimulus (bacon) in nose-poke arena, nose-poke behavior measured.

Figure 2

Mean (+SEM) body weight of rats at 4 and 12 months of age. At both ages, Ob rats weighed more than Le rats (*p<0.001), and food restriction decreased body weight of rats of the same strain (#p<0.001).

Figure 3

Mean (+SEM) nose-poke entries at 4 and 12 months of age at baseline (B) and when rats were exposed to a novel (N) and familiar (F) food olfactory stimulus. At 4 months of age, ObU rats nose-poked more than any other group in the familiar session, and ObU rats were the only group to exhibit a significant increase in nose-poke behavior from the B and N sessions to the familiar session. At 12 months of age, Ob rats performed more nose-pokes than Le rats in the N and F sessions, and only Ob rats showed an increase in seeking behavior between the B and F sessions. *p<0.05, **p<0.01, ***p<0.001.

Figure 4

Linear regression analyses performed between food intake and nose-poke entries. Analyses were performed separately for each session (baseline, novel, and familiar) at each age (4 and 12 months old). At 4 months of age, there was a significant positive correlation between these measures in the F session (p<0.001). At 12 months of age, there were significant positive correlations between body weight and nose-poke entries in the N (p<0.05) and F (p<0.01) sessions.

Figure 5

Linear regression analyses performed between body weight and nose-poke entries. Analyses were performed separately for each session (baseline, novel, and familiar) at each age (4 and 12 months old). At 4 months of age, there was a significant positive correlation between these measures in the F session (p<0.01). At 12 months of age, there were significant positive correlations between body weight and nose-poke entries in the N and F session (p<0.001 for both).