Role of Bactericidal Peptidoglycan Recognition Proteins in Regulating Gut Microbiota and Obesity
Abstract
The many advancements made by humans often come at a price. Current farming practices have made food easily available and very affordable in many countries, which has led to an overconsumption of food and foods that are rich in calories. The increased food intake combined with a sedentary lifestyle are the primary causes of an epidemic in obesity. Obesity is defined as excessive fat accumulation that may impair health. Adults (20 years and older) with a body mass index (BMI) of 30 and above are classified as being obese. In the United States, 35% of adults are obese. Moreover, Veterans have additional risk factors for obesity, which include spinal cord injuries and post-traumatic stress disorder syndrome, and 7 out of 10 of Veterans under the VA healthcare system are either obese or overweight. These numbers are of great concern because obesity increases the risk for developing metabolic diseases, which are collectively referred to as metabolic syndrome, and includes diabetes, heart disease, stroke and certain types of cancer. These diseases greatly reduce the quality of life and increase the risk of disease. Obesity and metabolic syndrome are also a major burden on the healthcare system. Though the primary cause of obesity is an excess of caloric intake over expenditure, genetic and environmental factors play a significant role in its development. Thus, each individual s genetic composition, the food they eat, and their lifestyle determine whether they will become obese and develop metabolic syndrome. In addition, the human gut is home to more than a trillion bacteria, and these bacteria are thought to play a major role in the development of obesity. The types of bacteria that are present in the gut are not identical between different individuals, and this difference is once again due to each individual s genetic composition, the food they eat, and their lifestyle. Obese individuals may have bacteria that promote obesity. However, the host genes that maintain beneficial gut bacteria are poorly understood. Furthermore, the identities of bacteria that promote obesity are also poorly understood. Peptidoglycan recognition proteins (Pglyrps) are proteins present in all mammals. They are involved in innate immunity, which is the first line of defense. Pglyrps recognize and kill bacteria and are required for maintaining a healthy gut microflora. In the absence of Pglyrps, the gut bacteria are altered, and the altered bacterial population promotes inflammation and is more efficient at harvesting energy from the diet. Bacteria that induce inflammation and have an increased capacity for energy output are known to promote obesity. However, it is not known whether Pglyrp-controlled gut microflora promotes obesity and metabolic syndrome. The hypothesis for the current project is that the innate immunity bactericidal proteins Pglyrps protect from inflammation, obesity, and metabolic syndrome by promoting a healthy gut microbiota. This hypothesis will be tested in an animal model of obesity. Mice that are wild-type for Pglyrp or deficient for Pglyrp will be given food that is high in fat content. This diet is similar to the fatty foods consumed by many people and implicated in the development of obesity. Mice will be monitored for weight gain, levels of glucose, cholesterol, and triglycerides, and for the development of insulin resistance, which indicates prediabetes or diabetes. In the second part of the project, the role of Pglyrp-controlled microflora in regulating sensitivity to obesity and metabolic syndrome will be tested. Gut bacteria from mice that are wild-type for Pglyrp or deficient for Pglyrp will be transplanted into wild-type germ-free mice and transplanted mice will be maintained on a high-fat diet and assayed for weight gain, levels of glucose, cholesterol, and triglycerides, and for the development of insulin resistance. The results from this project will increase our understanding of g
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510219
Entities
People
- Dipika Gupta
Organizations
- Indiana University – Purdue University Indianapolis
- United States Army