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http://hdl.handle.net/11375/22661
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DC Field | Value | Language |
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dc.contributor.advisor | Schertzer, Jonathan | - |
dc.contributor.author | Cavallari, Joseph | - |
dc.date.accessioned | 2018-03-16T19:23:56Z | - |
dc.date.available | 2018-03-16T19:23:56Z | - |
dc.date.issued | 2018 | - |
dc.identifier.uri | http://hdl.handle.net/11375/22661 | - |
dc.description.abstract | Intestinal dysbiosis contributes to obesity and insulin resistance, but intervening with antibiotics, prebiotics, or probiotics can be limited by specificity or sustained changes in microbial composition. Postbiotics include bacterial components such as lipopolysaccharides, which have been shown to promote insulin resistance during metabolic endotoxemia. The data presented in this thesis demonstrates that bacterial cell wall-derived muramyl dipeptide (MDP) is an insulin-sensitizing postbiotic that requires the nucleotide oligomerization domain 2 (NOD2) protein. Injecting MDP lowered adipose inflammation and reduced glucose intolerance in obese mice without causing weight loss. MDP reduced hepatic insulin resistance during obesity and low-level endotoxemia. NOD1-activating peptidoglycan worsened glucose tolerance. The transcription factor interferon regulatory factor 4 (IRF4) distinguished opposing glycemic responses to different types of peptidoglycan. IRF4 was dispensable for exacerbated glucose intolerance via NOD1, but was required for MDP/NOD2-induced insulin sensitization and lower metabolic tissue inflammation during obesity and endotoxemia. | en_US |
dc.language.iso | en | en_US |
dc.title | THE METABOLIC AND INFLAMMATORY EFFECTS OF NUCLEOTIDE OLIGOMERIZATION DOMAIN (NOD) PROTEIN SIGNALING DURING OBESITY AND BACTERIAL STRESS | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Biochemistry and Biomedical Sciences | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Doctor of Philosophy (PhD) | en_US |
dc.description.layabstract | Obesity is associated with insulin resistance, which is the primary predictor of type 2 diabetes. This research aims to understand the relationship between obesity, insulin, and diabetes by investigating the immune system. Inflammation contributes to insulin resistance during obesity. Inflammation is controlled by the immune system, which normally protects the body against disease. Good bacteria living inside the gut are beneficial because they aid digestion and increase nutrient absorption. Studying how bacteria interact with the immune system is important because microbes activate inflammatory responses. Therefore, different bacteria might be critical in preventing or promoting insulin resistance and diabetes during obesity. This research investigates the therapeutic effects of small compounds found in certain types of bacteria that interact with the immune system. These compounds activate specific immune responses and might be used as a new type of drug based on a "probiotic" health strategy. Bacterial compounds may reduce the amount of inflammation during obesity, thereby reducing the rates of type 2 diabetes. | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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cavallari_joseph_f_201712_phd.pdf | 16.61 MB | Adobe PDF | View/Open |
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