Dottorato in FARMACOLOGIA E TOSSICOLOGIA

Titolo della tesi: Prospects for new drugs to treat aberrant eating patterns: possible role of Oleoylethanolamide

Obesity is a complex pathology that occurs when energy intake exceeds energy expenditure and is characterized by the accumulation of dysfunctional adipose tissue which triggers metabolic stress response and induces a low-grade inflammatory chronic state at both central and peripheral levels. In the past years, research has focused on investigating the mechanisms involved in the control of feeding and energy balance to identify new pharmacological targets that could be potentially used in clinical practice for the treatment of pathological conditions characterized by multiorgan dysfunction, such as obesity. Among possible novel pharmacological targets, oleoylethanolamide (OEA) seems to be of particular interest based on its anti-obesity, anti-inflammatory, and antioxidant effects; OEA belongs to the lipid family of the N-acylethanolamines (NAEs) and is a potent endogenous ligand for peroxisome proliferator-activated receptor (PPAR)-α, a nuclear receptor involved in the transcriptional regulation of lipid metabolism, neuroplasticity and inflammation. In the present work was investigated in depth the effect of exogenous administration of OEA on molecular mechanisms involved in obesity-related alterations and on the endogenous oxytocinergic strictly implicated in both homeostatic and non-homeostatic control of eating behavior. Particularly, by using a diet-induced obesity (DIO) rat model we evaluated the impact of chronic peripheral administration of OEA on both brain and peripheral alterations. Moreover, we deeply investigated the possible alteration of the endogenous oxytocinergic system in different preclinical models of aberrant eating pattern (binge eating female rats, DIO rats and cafeteria rats models) and furthermore we assessed if the direct or indirect pharmacological manipulation of OEA system might impact such systems. In conclusion, the results reported in this work have the potential to unravel new targets for the development of pharmacological treatments for obesity and eating disorders, two major health problems worldwide.