The role of brain mu-opioid receptor and food environment in the development of obesity

Yale University, New Haven CT

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Abstract

DESCRIPTION (provided by applicant): Obesity has reached epidemic proportions worldwide. An understanding of why this epidemic has occurred is essential for therapeutic treatments to be developed. The availability of foods high in fat and sugar is thought to play a major role in th obesity epidemic. The brain controls feeding behavior by driving the want to eat these foods that are high in calories. The brain normally perceives signals of fullness or hunger which in turn tell a person to stop or start eating, respectively. These signals are thought to be disrupted in obesity. The proposed research aims to understand the brain circuits involved in feeding regulation and how these circuits are disrupted in obesity. This research utilizes a rat model in which rats are either genetically predisposed to become obese or not. When these rats are placed on high fat diets, they either become obese (obese prone) or remain lean (obese resistant). These obese prone rats have disruption in critical brain pathways involved in feeding regulation that leads to overconsumption of high fat foods and, ultimately, obesity. Specifically, the ?-opioid receptor is elevated in the brain of obese rats and may lead to disruption in pathways involved in food reward and satiety. Manipulation of ?-opioid receptor through knockdown or overexpression within these brain regions will be done to understand how food choice and body weight are disrupted. Furthermore, neurons within brain regions involved in food reward will be activated or inhibited to identify how these neuronal circuits regulate a choice between normal food and high fat food. Results from these experiments will deepen our understanding of how the brain perceives fullness and the desire to eat high fat and high sugar foods and how to correct the disruption that occurs in obesity.