EFFECTS OF OLEOYLETHANOLAMIDE SUBCHRONIC TREATMENT ON FOOD INTAKE, BODY WEIGHT AND GUT MICROBIOTA COMPOSITION IN NORMAL AND HISTAMINE DEFICIENT MICE: A PRELIMINARY STUDY

Energy balance is an equilibrium between the amount of energy extracted from the diet and the amount expended and is regulated by a complex interplay between central and peripheral factors. We demonstrated that the fatderived satiety factor oleoylethanolamide (OEA) requires the integrity of the central histaminergic system to fully exert its hypophagic action. Recent evidence suggests that the gut microbiota play a role in energy harvest, storage, and expenditure and its composition was shown to differ in lean and obese humans and animals and to change rapidly in response to dietary factors. Here we evaluate the effects of OEA sub-chronic treatment on food intake, body weight and gut microbiota composition as well as investigate the role of the histaminergic system in such effects. Histidine decarboxylase knock out (HDC-KO) mice and wild type (WT) littermates received daily i.p. injections of OEA (10 mg/kg, n = 4–5) or vehicle (PEG:Tween80:saline 5/5/ 90, n = 4–5) for 11 days, 1 h before dark onset. Faecal samples were collected after the 1st, 4th and 11th treatment day. DNAs were extracted and sequenced on a Roche 454 GS FLX? platform for the analysis of the V3–V5 region of the bacterial 16SrRNA gene. Food consumed 1 h after OEA treatment and cumulative food consumption at the end of treatment were significantly reduced in WT mice, with respect to vehicle-treated controls, but not in HDCKO mice. A significant reduction in body weight was also observed in OEA-treated WT mice with respect to vehicletreated animals, while no significant changes were observed in OEA-treated HDC-KO mice with respect to controls. In agreement with the decrease of weight, an enrichment of the phylum Bacteroidetes and a reduction of Firmicutes emerged in the group of OEA-treated WT mice. This trend in terms of phyla, is associable to the appearance of a ‘‘lean’’ microbiota instead of an ‘‘obese’’, where the trends of the two phyla are reversed. We acknowledge the Joint Programming Initiative—A Healthy Diet for a Healthy Life for support of AMBROSIAC project.