Role of Bactericidal Peptidoglycan Recognition Proteins in Regulating Gut Microbiota and Obesity
Technical Report,01 Jul 2015,31 Dec 2017
The Trustees of Indiana University Indianapolis United States
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Purpose The goal of this project was to test the hypothesis that innate immunity protein peptidoglycan recognition protein 3 Pglyrp3 protects from inflammation, obesity, and metabolic syndrome by promoting a healthy gut microbiota. Scope The results from this project will increase our understanding of genetic factors that promote obesity and metabolic dysfunction and the role of gut bacteria in the development of metabolic disease. These studies will facilitate future development of novel approaches for prevention and treatment of obesity and associated diseases and may include use of Pglyrp-controlled microbiota to restore and maintain beneficial bacteria. Such novel approaches are essential in order to improve the health of military personnel, veterans, and their family members. Major findingsPglyrp3-- mice on high fat diet HFD gained significantly less body mass and had significantly less adipose tissue and steatosis than WT mice on HFD. Pglyrp3-- mice on HFD had lower serum triglycerides and developed significantly less glucose intolerance than WT mice on HFD. We further determined that the gut microbiota is altered in Pglyrp3-- mice on HFD compared with WT mice on HFD. Up-to-date report of results and significance Our results demonstrate that innate immunity proteins modulate the development of obesity and metabolic disease in mice. Pglyrp3 predisposes to diet-induced weight gain, hyperlipidemia, increased adiposity, steatosis, and development of glucose intolerance. To determine the role of the gut microbiota in the development of metabolic disease, we colonized Swiss Webster WT germ free mice with Pglyrp3-- HFD microbiome or WT HFD microbiome. In these initial experiments we did not get a difference in weight gain or in metabolites between the two groups of colonized mice. In future experiments we will use BALBc germ free mice to establish the role of the Pglyrp3-- HFD microbiome in development of metabolic dysfunction and obesity.
- Medicine and Medical Research
- Anatomy and Physiology