Grant: Operating Grant - Priority Announcement: INMD Start Up Funds (bridge funding)

Obesity is poised to be one of the major health threats to the current generation of Canadians. Nearly 1/2 of Canadians are overweight and 1/3 are obese. The health consequences of obesity such as heart disease, diabetes and cancer have a significant impact on the length and quality of life of Canadians. However little is known about the mechanisms that allow obesity to develop. Obesity results when more energy is consumed than is used in day to day life. All animals including humans have systems designed to signal when one has eaten enough - this is termed "satiety". Many of these satiety signals are transmitted from the gut to the brain through sensory nerve fibres known as vagal afferents. These nerves can detect the presence of food in the gut two ways; the first is though stretch of the gut as it fills with food. The second is though the release of so called "satiety hormones" and other chemicals that then activate these nerves, sending a message to the brain telling it to stop eating. Why can individuals eat in excess of their daily requirements resulting in the development of obesity? We hypothesize that overconsumption of high fat foods results in a "desensitization" of these satiety signaling vagal afferents. The result of this is that the number and strength of signals sent to the brain telling the individual to stop eating are decreased .We plan to test responses of these nerves to satiety hormones using electrical recording techniques. We will compare responses in obese mice (fed a diet with 60% calories from fat) and lean mice (fed a diet with 10% calories from fat). We expect that responses to these satiety hormones will be decreased in obese mice. If we do find these differences, we will then attempt to determine: 1. Are the changes specific to satiety hormones, or are the nerves less sensitive overall? 2.Are the changes are due to decreases in levels receptors for these hormones, or alternatively the way in which the cells respond to those hormones.