Transcriptional effects on hypothalamic inflammatory mediators in an animal model of binge eating.

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 could play a role in the onset and maintenance of eating-related maladaptive behavior. These studies mainly assessed serum levels of pro-inflammatory cytokines in patients suffering from eating disorders. However, markers of inflammation can be altered in the brain while remaining unchanged in the periphery. Indeed, pro-inflammatory cytokines can regulate food intake directly by affecting the hypothalamic neurons implicated in the regulation of eating behavior and appetite or even indirectly via their impact on neuropeptide-neurotransmitter functionality. In the present study we measured the levels of expression of different components of cytokine systems (IL-1, IL-6, IL-18, IL-33, 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-eating behavior for highly palatable food is not shown during the estrus phase. We found decreased levels of IL-1Ra and IL-33 mRNAs in both the hypothalamic regions evaluated in non-estrous rats developing binge-like eating behavior. In the same group of animals, specific differences in the regulation of the expression of components of the IL-18/IL-18R system were found in the anterior-tuberal hypothalamus possibly leading to a general impairment of the functionality of this cytokine in presence of stress-induced binge-eating behavior. Our data suggest that targeting inflammatory markers centrally could be possible to prevent that excessive palatable food consumption turn into bingeing-related eating disorders.