Nociceptin/orphanin FQ-induced food intake and cocaine amphetamine regulated transcript gene expression in strains derived from rats prone (WOKW) and resistant (Dark Agouti) to metabolic syndrome

In previous work, we observed that N/OFQ-induced hyperphagia is greater in DA rats, animals resistant to metabolic syndrome, than in WOKW animals, which are prone to this disease. We attributed this difference to the fact that these two strains have different Cart gene sequences and expression. As a preliminary approach to pursue this hypothesis, the present work focused on Cart gene expression by developing from DA and WOKW rats various congenic animals with exchanges of metabolic syndrome-related QTL's of different chromosomes (3, 5, 10 and 16), and analyzing their N/OFQ-induced (2.1, 4.2, and 8.4nmol/rat) food intake in terms of their CART gene expression and N/OFQ hypothalamic immunostaining. Two groupings emerged, the first, with strains 3a, 3b, and 5a with elevated N/OFQ-induced feeding similar to that of the DA rats, and the second, with strains 16 and 10, with lower feeding, like the WOKW rats. There was a perfect correlation between Cart gene expression and N/OFQ-induced feeding data at 30min for the strains DA, 3a, 3b, 5 in the first group, and 16 and WOKW for the second, but not for strain 10. As expected, the strains with low content of Cart gene expression had elevated N/OFQ-induced feeding, but contrary to expectations, strain 10, with the lowest Cart gene expression, exhibited low N/OFQ-induced feeding, on the order of that of the WOKW rats. A comparable trend was observed with N/OFQ hypothalamic immunostaining. This anomaly may be due to other satiety-related factors involved in N/OFQ-induced feeding.