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

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.