Homeostatic and hedonic gene expression signatures in rats bred for divergent intrinsic aerobic capacity maintained on high-fat diet

Burghardt PR, Krolewski DM, Dykhuis KE, Koch LG, Britton SL, Watson SJ, Akil H
Society for Neuroscience. 2011.


Selective breeding for intrinsic treadmill running capacity in rats has produced two divergent lines with high and low capacity for running (HCR and LCR, respectively) with distinct physiological and behavioral phenotypes. We have recently found that behavior in the novelty suppressed feeding paradigm differs between HCR and LCR rats that were maintained on high-fat diet (HFD) for six weeks as described by Dykhuis et al, (SfN Abstracts, 2011), indicating that an individual’s metabolic phenotype, dietary history, and feeding status influence their behavioral repertoire for coping with conflict. To begin to determine the neural correlates of these behavioral differences we investigated gene expression patterns in brain regions that regulate hedonic and homeostatic aspects of food intake in HCR and LCR rats following ad libitum food intake or a 24-hour fast. Body weight and ad libitum food intake were monitored in HCR and LCRs maintained on HFD prior to fasting for 6 weeks. After 6 weeks a subset of each phenotype was fasted for 24-hrs prior to tissue collection, while the remaining rats were allowed open access to food. As previously reported, LCR rats weigh more and consume more chow than HCR rats. Expression of mRNA for neuropeptides in the arcuate nucleus of the hypothalamus (Arc) along with mRNA for neuropeptides and dopaminergic receptors in the striatum and nucleus accumbens (NAc) were measured by in situ hybridization. LCR exhibited a larger increase in agouti-related peptide mRNA in responses to an overnight fast compared to HCR rats. POMC in the Arc also trended towards differential response with HCR rats showing a relative increase in expression to fasting, while that of LCR rats decreased which is similar to the arcuate POMC mRNA response to fasting of these rats maintained on standard chow (Burghardt, et al, SFN abstracts 2010). Expression of Cocaine-Amphetamine-Regulated Transcript (CART) and dopamine receptor mRNA in the NAc are currently being analyzed. Taken together, this study shows that following a 24-hr fast LCR rats exhibit an expression signature in regions related to homeostatic and hedonic processes geared towards increased feeding compared to HCR. These results indicate that an individual’s metabolic phenotype and feeding state can differentially alter patterns of gene expression in brain regions involved in the homeostatic and hedonic response to food and may influence behavioral strategies employed to cope with environmental novelty.