Epigenetic regulation of nociceptin/orphanin FQ and corticotropin-releasing factor system genes in frustration stress-induced binge-like palatable food consumption

Abstract

Evidence suggests that binge eating may be caused by a unique interaction between dieting and stress. We developed a binge-eating model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after a 15-minute exposure to the sight of the palatable food (frustration stress). The aim of the present study was to investigate the regulation of the stress neurohormone corticotropin-releasing factor (CRF) system and of the nociceptin/orphanin FQ (N/OFQ) system genes in selective rat brain regions, using our animal model. Food restriction by itself seems to be responsible in the hypothalamus for the downregulation on messenger RNA levels of CRF-1 receptor, N/OFQ and its receptor (NOP). For the latter, this alteration might be due to selective histone modification changes. Instead, CRF gene appears to be upregulated in the hypothalamus as well as in the ventral tegmental area only when rats are food restricted and exposed to frustration stress, and, of relevance, these changes appear to be due to a reduction in DNA methylation at gene promoters. Moreover, also CRF-1 receptor gene resulted to be differentially regulated in these two brain regions. Epigenetic changes may be viewed as adaptive mechanisms to environmental perturbations concurring to facilitate food consumption in adverse conditions, that is, in this study, under food restriction and stressful conditions. Our data on N/OFQ and CRF signaling provide insight on the use of this binge-eating model for the study of epigenetic modifications in controlled genetic and environmental backgrounds.

Transcriptional regulation of the endocannabinoid system in a rat model of binge‐eating behavior reveals a selective modulation of the hypothalamic fatty acid amide hydrolase gene

“…3.1 | Binge-eating behavior in rats exposed to food restriction and binge-eating test As reported in previous studies Micioni Di Bonaventura et al, 2014;Pucci et al, 2016), we found that rats lose weight during the food restriction period but they regain it during the subsequent free-food period. On the last day of the BE FIGURE 2 Schematic representation of the rat faah gene and the 5 0 upstream region.…”

“…In this work, the combination of stress and repeated food restriction induced binge-eating behavior for highly palatable food in female rats as shown previously (Cifani et al, 2009;Piccoli et al, 2012), where regulation of nociceptin/orphanin FQ and corticotropin-releasing factor genes was reported as a potential contributor Pucci et al, 2016). Here, we extended our previous investigations to the role of ECS gene regulation in the same animal model.…”

“…Stress and food restriction-induced changes in the expression of ECS genes in several brain regions were assessed by qRT-PCR as described previously (D'Addario et al, 2017;Pucci et al, 2016). Specifically, expression of cnr1, cnr2, the gene coding for CB receptors, CB 3 (GPR55) receptors and TRPV1 was analyzed as well as the expression of the enzymes involved on biosynthesis (DAGL and NAPE-PLD) and degradation (MAGL and FAAH) of eCBs.…”

Hypothalamic CRF1 receptor mechanisms are not sufficient to account for binge‐like palatable food consumption in female rats

“…Cifani et al, 2010; C. Cifani et al, 2009; Micioni Di Bonaventura, Cifani, et al, 2012; Micioni Di Bonaventura, Vitale, et al, 2012; Pucci et al, 2015), body weight of rats was reduced during the 4 days of food restriction, but immediately afterwards the animals increased their food intake and rapidly recovered their body weight to levels of controls by the end of each cycle. On the test day body weight of animals, as well as their food intake in the previous 24 h, were not significantly different among the groups (data not shown).…”

Modulation of Pain Sensitivity by Chronic Consumption of Highly Palatable Food Followed by Abstinence: Emerging Role of Fatty Acid Amide Hydrolase

“…A recent systematic review (Torensma et al, 2016) included two studies suggesting that obese subjects have a lower pain threshold than nonobese subjects (Pradalier et al, 1981;McKendall and Haier, 1983), but four studies indicating that obese subjects have a higher one (Zahorska-Markiewicz et al, 1988;Miscio et al, 2005;Maffiuletti et al, 2011;Dodet et al, 2013). Other findings concluded that body mass index and body fat may influence the pain threshold (Bohnert et al, 2013;Price et al, 2013;Tashani et al, 2017;Torensma et al, 2017), and the intensity of the perception of stimuli changes proportionally with the levels of subcutaneous fat in the affected body area. Price et al (2013) reported that obese people have a higher pain threshold in the abdominal area compared to the hands and forearms.…”