Hypothalamic expression of inflammatory mediators in an animal model of binge eating

Abstract

Binge eating episodes are characterized by uncontrollable, distressing eating of a large amount of highly palatable food and represent a central feature of bingeing related eating disorders. Research suggests that inflammation plays a role in the onset and maintenance of eating-related maladaptive behavior. Markers of inflammation can be selectively altered in discrete brain regions where they can directly or indirectly regulate food intake. In the present study, we measured expression levels of different components of cytokine systems (IL-1, IL-6, IL-18, TNF-α and IFN-ɣ) and related molecules (iNOS and COX2) in the preoptic and anterior-tuberal parts of the hypothalamus of a validated animal model of binge eating. In this animal model, based on the exposure to both food restriction and frustration stress, binge-like eating behavior for highly palatable food is not shown when animals are exposed to the frustration stress during the estrus phase. We found a characteristic down-regulation of the IL-18/IL-18 receptor system (with increased expression of the inhibitor of the pro-inflammatory cytokine IL-18, IL-18BP, together with a decreased expression of the binding chain of the IL-18 receptor) and a three-fold increase in the expression of iNOS specifically in the anterior-tuberal region of the hypothalamus of animals that develop a binge-like eating behavior. Differently, when food restricted animals were stressed during the estrus phase, IL-18 expression increased, while iNOS expression was not significantly affected. Considering the role of this region of the hypothalamus in controlling feeding related behavior, this can be relevant in eating disorders and obesity. Our data suggest that by targeting centrally selected inflammatory markers, we may prevent that disordered eating turns into a full blown eating disorder.

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

“…In previous studies we observed that in the estrous phase of the ovarian cycle, female rats do not exhibit binge eating using our model (Alboni et al, 2017;Micioni Di Bonaventura et al, 2017) while in all other three phases, the rats exhibit binge eating without significant differences in intensity. Therefore, to control for the estrous cycle, immediately after the test on d 25, vaginal smears were collected and analyzed under microscope by an experimenter blind to treatment conditions.…”

“…This stress procedure has face validity as a model of the putative contributions of dieting and negative-valence states, to binge eating in humans (Association, 2013; Mathes, Brownley, Mo, & Bulik, 2009; Sanislow et al, 2010; Treasure, Claudino, & Zucker, 2010; Vannucci et al, 2015). Considering the high prevalence of binge eating in women (Hudson et al, 2007; Swanson et al, 2011), we used female rats, in which binge-like eating behavior varies across the estrus cycle (Alboni et al, 2017; Micioni Di Bonaventura et al, 2017), similarly to women (Culbert, Racine, & Klump, 2016; Edler, Lipson, & Keel, 2007; Klump et al, 2013; Schoofs, Chen, Braunig, Stamm, & Kruger, 2011) and this result increases the validity of the model that can be used in translational studies of the mechanism of binge eating behavior.…”

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

“…On day 25, the final test day, each group was exposed or not to stress (15 min) (see Figure 1 for details). We found in a previous study that stress-induced BE in our model is not observed during the estrous phase (Alboni et al, 2017;Micioni Di Bonaventura, Lutz et al, 2017). In these conditions, the animal was able to see the cup and the palatable food itself and could smell its odor.…”

A model of emotional stress‐induced binge eating in female mice with no history of food restriction

“…Indeed, stress‐related disorders are positively correlated with bingeing episodes and are more prevalent in females, underscoring the importance of designing ethologically relevant animal models to investigate the interplay between stress and bingeing behaviors . In 2009 Cifani et al reported an elegant model of emotional stress‐induced binge eating in female rats where repeated cyclic caloric restriction induced binge eating of highly palatable food when exposed to a frustrative stressor . This protocol models the impact of “yo yo dieting” on binge eating behavior.…”

“…[12][13][14][15] In 2009 Cifani et al reported an elegant model of emotional stress-induced binge eating in female rats where repeated cyclic caloric restriction induced binge eating of highly palatable food when exposed to a frustrative stressor. 5,7,16,17 This protocol models the impact of "yo yo dieting" on binge eating behavior. We wanted to extend these findings to establish whether this behavior can be observed in the absence of a history of caloric restriction and could be readily modeled in mice.…”