StudioCommissionato_DI MARZO_Effects of OlGly and OlSer on food addiction (DCM.AD007.064)

Thematic area

Chemical sciences and materials technology

Project area

Structure responsible for the research project

Institute of biomolecular chemistry (ICB)

Project manager

VINCENZO DIMARZO
Phone number: 0818675093
Email: vincenzo.dimarzo@icb.cnr.it

Abstract

The feeding process is required for basic life, influenced by environmental cues and tightly regulated according to the demands of the internal milieu by regulatory brain circuits. Although eating behaviour cannot be considered "addictive" under normal circumstances, people can become "addicted" to this behaviour, mechanistically similar to how some people are addicted to drugs. In animal models, the opioid, endocannabinoid, orexin and ³-aminobutyric acid (GABA) systems have crucial roles as mediators in the "liking" experience by regulating activity in a network of hedonic hotspots involving the nucleus accumbens, ventral pallidum and brainstem. Likewise, excessive "desire" for and "liking" of food, notably hyper-palatable food supplied by high fat diets (HFD), may play a role in overeating (Novelle and Diéguez, 2018 review). Furthermore, the understanding of the crucial role of gut microbes in addiction is increasing. Bradshaw & Leishman's study (2015) shows that olive oil is the richest source of precursors for bioactive lipids of the N-acyl amide and 2-acyl glycerol families, including the oleoyl-derivates of amino acids, such as N-oleoyl-glycine (OlGly) and N-oleoyl-serine.

Goals

In this study, we will seek to investigate the impact of OlSer and OlGly on feeding, locomotion, food reward and dopaminergic (DA) neuronal activity in a mouse model of obese mice fed with high fat diet (HFD)±olive oil compared to mice fed with standard diet (SD)±OlGly or OlSer intreperitoneal injection. Moreover, we will investigate the possible modification of the gut microbiome composition in response to exposure to these diets and compounds, to check whether a dysfunctional microbiota following HFD and contributing to food addiction can be thereby corrected. We shall also determine if these compounds and their chemical congeners are produced in the brain and gut by using high resolution IT-TOF LC-MS/MS and if, they are responsible for altered behaviours like feeding, locomotion, food reward which are dependent from dopaminergic neuronal activity possibly through PPARa pathway. To this purpose we will perform confocal imaging and electrophysiological studies of the neuronal firing amplitude and frequency of dopamine (DA) producing neurons in the VTA of transgenic TH-eGFP mice fed with SD ± OlGly/OlSer injection or HFD±Olive oil.

Start date of activity

18/03/2019

Keywords

dopamine, tyrosine hydroxylase, reward

Last update: 16/04/2024