American Diabetes Association research supports projects aimed at understanding the biology of appetite regulation and metabolism, the identification of new treatment targets, and trials exploring pharmacological and behavioral interventions to enhance and sustain weight loss.
Juli Bai, PhD
The University of Texas Health Science Center at San Antonio
Project: The role of the cGAS-cGAMP pathway in regulating energy homeostasis
“Increasing energy expenditure shows great metabolic benefits which helps organisms defend against obesity and metabolic illness. This award will allow me to understand the key molecular mechanism of energy homeostasis and will help broaden our understanding of the pathogenesis of obesity and its related chronic metabolic disease.”
The problem: While traditional ways of losing weight like dieting and exercise can be effective for some, most people cannot maintain weight loss produced through these methods. However, tools to help people lose and sustain weight loss are limited. New ways to promote and sustain weight loss are needed and could be an important tool to reduce rates of type 2 diabetes.
The project: Dr. Bai has identified a gene which influences the amount of energy that is expended. Mice harboring a mutation in this gene have reduce energy expenditure, leaving them at greater risk for obesity and diabetes. In this project, Dr. Bai is working to further investigate this gene and to determine if it might be a therapeutic target to help people lose weight.
The potential outcome: Translation of this project to the clinic could result in a medication to increase energy expenditure and help to tip the energy balance scale towards sustained weight loss.
Mete Civelek, PhD
University of Virginia
Project: Dissecting the KLF14-regulated transcriptional network in adipocytes
“Both of my parents live with type 2 diabetes. My mother's father died from complications related to type 2 diabetes. Therefore, I have closely witnessed the difficulty in managing this disease and want to help families living with it. Even one new drug that targets a previously unknown disease pathway will bring relief to millions of people around the world. This award will enable my laboratory perform experiments to understand a novel pathway we discovered through human genetics studies in great detail and test its potential as a therapeutic target.”
The problem: Metabolic Syndrome, which includes obesity, is a primary cause of cardiovascular disease and diabetes. Understanding the biologic networks that underlie the complex interactions in metabolic syndrome traits is required for diabetes prevention, diagnosis, and treatment.
The project: Dr. Civelek recently identified a gene, called KLF14, whose product regulates a group of genes in human fat tissue. This gene is implicated in how fat is stored in our bodies, and certain genetic variants of KLF14 increase one’s risk for developing type 2 diabetes. This project will attempt to further understand of how this gene alters the storage of fat and to identify genetic variants in humans that may affect its function.
The potential outcome: Obesity has both genetic and environmental causes. This project has the potential to outline one such genetic factor that influences how fat is stored, and may help lead to personalized medicine and new ways to enhance weight loss.
Robert V. Considine, PhD
University of Indiana
Project: Effect of bariatric surgery on the central neural response to sweet taste
“I have spent my entire career studying how people become obese and how this leads to the development of diabetes. I feel strongly that many cases of diabetes can be prevented if we can reduce the number of people who are obese. Understanding how Roux-en-Y surgery reduces the preference for sweet taste will assist the development of nonsurgical methods to reduce consumption of sweetened high calorie foods and beverages.”
The problem: Evidence suggests that following Roux-en-Y gastric bypass (RYGB) surgery patients decrease their intake of sweetened food and beverages. This implies that RYGB surgery changes how the brain controls food intake. However, which brain areas are responsible for this effect of RYGB on the brain response to sweet taste has not been investigated.
The project: To test the effect of RYGB on sweet taste preference in humans Dr. Considine will use functional magnetic resonance imaging – a way to visualize activity in different brain regions – and administer sugar to the tongue. His goal is to determine how RYGB surgery changes sweet preference compared to other weight loss procedures, which have not been reported to have this effect.
The potential outcome: Understanding the mechanisms through which RYGB alters sweet taste perception is critical for developing nonsurgical interventions to reduce consumption of sweetened high calorie foods and beverages.