The Role of Lateral Hypothalamus Orexin Glucose-Inhibited Neurons in Binge-Eating Disorder
Abstract
Fiscal Year 2018 Topic Area of Encouragement: This research will advance the understanding of the biological and environmental factors that influence Eating Disorders. Eating disorders are the most highly stigmatized psychiatric illnesses and often underdiagnosed. Binge eating disorders (BED) and bulimia nervosa (BN) are two eating disorders that are reported to be overrepresented in Veteran populations, especially in females. Because an eating disorder disqualifies entry into military service, the increased prevalence of BED and BN in Veteran populations suggests that the physical and psychological demands of active duty influence the susceptibility for developing eating pathologies. Active military Service members are significantly more likely to report binge eating (consuming a large amount of food in a short period without control) in conjunction with intermittent fasting or extreme physical activity. These behaviors can persist past active service and lead to significant and lifelong health problems in Veterans. This problem is exacerbated by the intractable and drug-resistant nature of BED and BN. While the role of psychological stress and combat-related trauma have a known influence on BED and BN, the influence of dietary factors or habits on BED and BN are poorly understood. Indeed, a history of dieting is a risk factor for developing an eating disorder. The strict body weight and physical fitness requirements for military personnel in particular foster the development of habitual dieting or restrictive eating. As a result, the military and Veteran populations may be placed at greater risk for developing eating disorders than the general population. Thus, research strategies designed to investigate the mechanisms sustaining bingeing behaviors, especially as it pertains to the addictive nature of highly palatable rewarding foods, would provide a stronger foundation for developing clinically effective treatment strategies for improving the quality of life for military Service members and Veterans afflicted with eating disorders. This proposal will investigate the mechanism(s) by which prior caloric restriction and dieting contribute to the development of persistent and drug-resistant eating disorders such as BED and BN. In order to do this, we will use our novel rodent model of binge-type eating in which prior food restriction enhances binge eating of palatable food and renders this behavior resistant to currently available drug therapies. Since the brain controls food intake, we will focus on groups of cells (neurons) that are known to influence the desire to overeat palatable, rewarding foods (e.g., sugary fatty treats). Specific neurons in the brain that release a protein known as “orexin” are inhibited when blood sugar (glucose) increases and activated when blood glucose decreases. We found that the degree to which these orexin neurons are activated by low glucose increases after food restriction. Activation of these orexin neurons in the lower glucose levels associated with food restriction leads to persistent activation of downstream neurons, which release “dopamine.” These dopamine neurons then activate brain regions that stimulate reward feeding and play a role in addiction. Interestingly, rodents became less motivated to seek out sugary fatty treats (chocolate) when we increased the glucose levels surrounding their orexin neurons. Based on our findings, we hypothesize that the enhanced activity of orexin neurons in low glucose after food restriction persistently activates the dopamine neurons, leading to a sustained and drug-resistant desire to overeat palatable rewarding foods. This partnered proposal will combine the strengths of the laboratories of Dr. Nicolas Bello and Dr. Vanessa Routh. Dr. Bello, an expert in feeding behavior, developed the binge-type eating model above. Dr. Bello will determine whether inhibiting orexin neurons during food restriction will reduce binge-type
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910015
Entities
People
- Vanessa H Routh
Organizations
- Rutgers University
- United States Army