Gender differences in Nociceptin/Orphanin FQ-induced food intake in strains derived from rats prone (WOKW) and resistant (Dark Agouti) to metabolic syndrome: a possible involvement of the cocaine- and amphetamine-regulated transcript system

Abstract

Our previous study found that when injected with Nociceptin/Orphanin FQ (N/OFQ) into the brain, male Dark Agouti (DA) rats, which are resistant to metabolic syndrome, have greater hyperphagia than male Wistar Ottawa Karlsburg W (WOKW) animals, which are prone to this disease. We attributed this difference to the fact that these two strains have different cocaine-amphetamine regulated transcript peptide (Cart) gene sequences and expression. In order to address this hypothesis, the present work focused on sex differences and analyzed not only male but also female N/OFQ-induced (0.25 and 0.5 nmol/ rat) food intake in terms of their Cart and N/OFQ receptor gene expression in the hypothalamic area. In N/OFQ-naive WOKW females, cart gene expression is extremely elevated compared to N/OFQ-naive WOKW males. When male and female WOKW littermates are stimulated with N/OFQ, the food intake of females is significantly lower than that of the males. Granted, the N/OFQ feeding behavior experiments were not performed on the animals measured for Cart gene expression, but nonetheless, the responses observed in littermates point to an interesting avenue for further inquiry.

Role of Nociceptin/Orphanin FQ-NOP Receptor System in the Regulation of Stress-Related Disorders

“…Additionally, N/OFQ might induce hyperphagia by inhibiting the endogenous cocaine and amphetamine-regulated transcript (CART) [ 231 , 232 , 233 ], which is another anorectic peptide also regulated by leptin [ 234 ]. Beyond the modulation of these hypothalamic mechanisms, N/OFQ modulates the activity of 5-HT neurons in the DRN (see above) which may also change feeding responses.…”

Cocaine-and-Amphetamine Regulated Transcript (CART) peptide attenuates dopamine- and cocaine-mediated locomotor activity in both male and female rats: Lack of sex differences

“…Interestingly, there are sex differences in CART peptide expression and function (Fagergren and Hurd, 1999, Rondini et al, 2004, Balkan et al, 2006, Gozen et al, 2007, Xu et al, 2010, Battistoni et al, 2011, Gerrits et al, 2011, Hostetler et al, 2011, Rodrigues et al, 2011, Bloem et al, 2012). Because of the findings that there are sex differences in (a) the effects of cocaine on DA in the NAc and (b) in CART peptide expression and function, we explored if there are sex differences in the effects of CART peptide on cocaine-induced LMA in rats.…”

A quadratically regularized functional canonical correlation analysis for identifying the global structure of pleiotropy with NGS data

“…We found that 30 out of 79 genes (38.0%) with rare variants significantly associated with 46 traits were reported association with some of them in the literatures. For example, PNOC which was associated with the 46 traits (p-value ≤ 1.63 × 10 −12 ), HOMA-IR (p-value ≤ 1.2 × 10 −7 ) and triglycerides (p-value ≤ 9.15 × 10 −9 ) was reported to be associated with insulin resistance [ 60 ] and triglycerides [ 61 ]. MIR409 which was associated with the 46 traits (p-value ≤ 2.77 × 10 −10 ), weight (p-value ≤ 1.65 × 10 −6 ), Hip (p-value ≤ 7.19 × 10 −7 ) and total lean mass (p-value ≤ 2.15 × 10 −6 ) was used as a weight loss biomarker [ 62 ].…”

“…Throughout this section, all p-values were calculated using QRFCCA. PNOC which was associated with the 46 traits (p-value ) was reported to be associated with insulin resistance 64 ) was used as a weight loss biomarker. 66 GAPDH which showed an association with the 46 traits (p-value ) was reported to be associated with creatinine.…”