Studies suggest that sugars, particularly glucose, have high post-ingestive, taste-independent metabolic rewards that drive intake and thus contribute to the obesity epidemic. Our goal was to develop a learning paradigm to probe molecular mechanisms underlying post-ingestive reward development. In our mouse model, we show that glucose-induced flavor preference occurs after a 30-minute training session during which fructose and glucose, each paired with a neutral flavor, are presented simultaneously. Using mice which lack sweet taste signaling, we demonstrate that post-ingestive glucose-induced flavor preference develops rapidly, is stable, and resists reversal. We furthermore show that preference development depends on K-ATP channel-dependent glucose sensing and leptin signaling. Similarly, glucose produces odor preference in C. elegans, which is enhanced by prior food withdrawal and by blocking glucose metabolism. Glucose-induced odor preference is mimicked by serotonin (released from NSM neurons) signaling through ser-4 receptors. Dopamine D1-like signaling produces, and the D2 agonist bromocriptine blocks, glucose-induced odor preference. Furthermore prior food withdrawal similarly regulates reward produced by serotonin, dopamine, or food, implying post-synaptic enhancement of sensitivity to serotonin and dopamine. These results suggest that glucose metabolism plays a key role in mediating both food-induced reinforcement and enhancement of that reinforcement by prior food withdrawal. These results along with known neuronal connectivity in C. elegans imply a novel circuit mediating food- and glucose-induced reinforcement. Our observations confirm that learned glucose-induced flavor preference is independent of taste or calories. We speculate that during a critical period early in life, flavor preferences are acquired in part due to association with glucose signaling, after which they persist independent of glucose signaling.
|Advisor:||Mobbs, Charles V.|
|Commitee:||Cagan, Ross, Routh, Vanessa, Russo, Scott, Salton, Stephen|
|School:||Icahn School of Medicine at Mount Sinai|
|School Location:||United States -- New York|
|Source:||DAI-B 75/02(E), Dissertation Abstracts International|
|Keywords:||Caenorhabditis elegans, Flavor preference, Glucose-induced, Mice, Molecular mechanisms, Postingestive reward|
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