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Analysis of novel risk factors influencing control of food intake and regulation of body weight
Objectives
The overall goal of this project is to investigate the role of oral and post-oral signaling pathways in the control of food intake and development of obesity.
The first objective is to determine whether obese prone rats have deficits in oral and postoral signaling pathways leading to hyperphagia and weight gain. It is unclear whether altered taste functions, intestinal nutrients chemosensation and susceptibility for obesity are common traits or acquired deficits to environmental factors.
The second objective is to identify the mechanisms (physiological, metabolical, neural) underlying the relationship between gut microbiota and regulation of energy balance in obese prone animals.
To meet these objectives, the project is divided into four main scientific tasks.
Task 1 will examine taste preference functions in obese-prone (OP) and obese-resistant (OR) rats on either chow or a high-energy high-fat (HE/HF) diet. Using a multi-bottle gustometer and brief access testing, we will test oral sensitivity to palatable tastants in OP and OR rats. The role of the DA system as a function of reward in mediating orosensory responses for sweet and fats will also be examined.
Task 2 examines postoral sensitivity to intestinal nutrients and gut peptides in OP rats and establishes the basic relationships between gustatory reward in HE/HF diet-fed rats and intestinal inhibitory feedback. Animals will receive intraintestinal infusion of nutrients (glucose or lipids) or systemic administration of GLP-1 agonist, a satiation peptide released in response to nutrients by the distal intestinal L-cell. In addition, the contribution of D1R and D2R in changes in nutrient sensitivity will be examined by using DA receptor antagonists.
Task 3 will examine the role of gut microbiota in control of food intake and obesity by interfering with, or modulating of, satiation, nutrient sensing, metabolism, and functions controlling appetite and energy homeostasis.
Task 4 will assess the cause/effect relationship between microbiota and obesity. This will be tested by conducting microbiota conventionalization studies from OP and OR animals to germ free animals. The objective is to determine whether the behaviour as well as all associated biological changes resultant of the phenotype and/or diet are transmittable and recapitulated in the GF animals.