Olive oil-derived endocannabinoid-like mediators inhibit palatable food-induced reward and obesity
Nicola Forte, Charlène Roussel, Brenda Marfella, Anna Lauritano, Rosaria Villano, Elvira De Leonibus, Emanuela Salviati, Tina Khalilzadehsabet, Giada Giorgini, Cristoforo Silvestri, Fabiana Piscitelli, Maria Pina Mollica, Vincenzo Di Marzo, Luigia Cristino
Abstract
N-oleoylglycine (OlGly), a lipid derived from the basic component of olive oil, oleic acid, and N-oleoylalanine (OlAla) are endocannabinoid-like mediators. We report that OlGly and OlAla, by activating the peroxisome proliferator-activated receptor alpha (PPARα), reduce the rewarding properties of a highly palatable food, dopamine neuron firing in the ventral tegmental area, and the obesogenic effect of a high-fat diet rich in lard (HFD-L). An isocaloric olive oil HFD (HFD-O) reduced body weight gain compared to the HFD-L, in a manner reversed by PPARα antagonism, and enhanced brain and intestinal OlGly levels and gut microbial diversity. OlGly or OlAla treatment of HFD-L mice resulted in gut microbiota taxonomic changes partly similar to those induced by HFD-O. We suggest that OlGly and OlAla control body weight by counteracting highly palatable food overconsumption, and possibly rebalancing the gut microbiota, and provide a potential new mechanism of action for the obeso-preventive effects of olive oil-rich diets.