Discipline: Biological Sciences
Subcategory: Cell and Molecular Biology
Aswad Jackson - Tougaloo College
Co-Author(s): Susan S. Baker, Wensheng Liu, Ricardo A. Arbizu, Robert D. Baker, and Lixin Zhu, University at Buffalo, Buffalo, NY
Evidence shows that gut microflora may play a role in the pathogenesis of Nonalcoholic fatty liver disease (NAFLD) through bacterial metabolites and bacterial cell wall components by increasing oxidative stress. D-amino acids (DAA) are major components of the bacteria cell wall. Peptidoglycan recognition protein 2 (PGLYRP-2) is an enzyme that releases DAA from bacterial cell wall. D-amino acid oxidase (DAO) is an enzyme that breaks down DAA and produces hydrogen peroxide. We look to examine the expression of DAO and PGLYRP-2 and determine if there is increased gene expression that might increase oxidative stress and contribute to the pathogenesis NAFLD. The gene expression of DAO and PGLYRP-2 in Non-alcoholic steatohepatitis (NASH) livers and normal controls (NC) were examined by microarray analysis and confirmed by quantitative real time PCR analysis (qRT-PCR). NASH patients showed an increased gene expression for DAO and PGLYRP-2 when compared to NC. We further used an animal model (rats) to test the same hypothesis. We compared a high fat (HF) to a high fat plus dextran sulfate sodium (HF+DSS) diet. DSS causes colitis and therefore causes elevated hepatic exposure of gut derived DAA. Using qRT-PCR, we found that the mRNA level of DAO gene was significantly increased in livers of rats treated with (HF+DSS) for 26 weeks, when compared to high fat group. We conclude that DSS treatment increased the hepatic DAO gene expression. Our research supports the novel mechanism of oxidative stress contributed by DAA from gut microbiome. This understanding may allow the development of integrated strategies to regulate intestinal microbiota in order to treat NAFLD. Future research may test the hypothesis at protein and activity levels.
References: Lau, E., Carralo, D., & Freitas, P. (2015, January). Hindawi Publishing Corporation. Gut Microbiota: Association with NAFLD and Metabolic Disturbances. Retrieved July 2015, from http://www.hindawi.com/journals/bmri/2015/979515/
Funder Acknowledgement(s): Funding was provided by CLIMB PRO (Professional), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo. Funding was also provided by Jackson Heart Study.
Faculty Advisor: Lixin Zhu,