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dc.contributor.authorDenko, Laura Michelleen_US
dc.date.accessioned2017-04-04T19:49:23Z
dc.date.available2017-04-04T19:49:23Z
dc.date.issued2012-06-21en_US
dc.identifier.otheretd-06292012-114135en_US
dc.identifier.urihttp://hdl.handle.net/10919/76808
dc.description.abstractObesity-related metabolic derangements have been linked to toll-like receptor 4 (TLR4), an innate immune system receptor, due to its role in proinflammatory pathways. Lipopolysaccharide (LPS), a gram-negative bacteria cell wall component, is the ligand for TLR4, and has been shown to be elevated in states of metabolic disease. Heightened levels of circulating endotoxin is termed metabolic endotoxemia and has been linked to systemic inflammation which is associated with obesity, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD). Immune cells exhibit a protective ability to develop endotoxin tolerance. The objective of this study was to determine if endotoxin tolerance exists in skeletal muscle cells, and if a condition that mimics a state of over nutrition, such as elevated levels of fatty acids, affect this tolerance. To this end, L6 skeletal muscle cells were treated with low (50 pg/mL)- and high (500 ng/mL)-doses of LPS, with and without the presence of free fatty acids (FFAs). Tolerance was assessed by measuring: 1) changes in mRNA expression of interleukin-6 (IL-6) and monocyte chemoattractant-1 (MCP-1) as markers of a pro-inflammatory response; and 2) mRNA levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1-°) and mitochondrial oxidative capacity via an XF24 Flux Analyzer (Seahorse Bioscience) as measures of the metabolic response. Tolerance to LPS was observed in response to low- and high-doses with MCP-1 mRNA transcription but not IL-6. Changes in PGC1-° and mitochondrial OCR exhibited a tolerant effect in response to the high dose of LPS but not the low dose. The addition of free fatty acids to LPS treatments did not prevent the tolerant effects under any conditions. In conclusion, LPS tolerance exists in skeletal muscle cells but appears to differ depending on pro-inflammatory target and LPS concentration. Additionally, fatty acids, in the current model, have no effect on LPS tolerance.
dc.language.isoen_USen_US
dc.publisherVirginia Techen_US
dc.rightsI hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Virginia Tech or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.en_US
dc.subjectTLR4en_US
dc.subjectendotoxinen_US
dc.subjectLPSen_US
dc.subjectskeletal muscleen_US
dc.titleCellular Reprogramming in Skeletal Muscle after Repeated Exposures to Endotoxinen_US
dc.typeThesisen_US
dc.contributor.departmentHuman Nutrition, Foods, and Exerciseen_US
dc.description.degreeM.S.en_US
thesis.degree.nameM.S.en_US
thesis.degree.levelmastersen_US
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen_US
dc.contributor.committeechairHulver, Matthew W.en_US
dc.contributor.committeememberDavy, Kevin P.en_US
dc.contributor.committeememberLi, Liwuen_US
dc.contributor.committeememberFrisard, Madlyn I.en_US
dc.type.dcmitypeTexten_US
dc.identifier.sourceurlhttp://theses.lib.vt.edu/theses/available/etd-06292012-114135/en_US
dc.date.sdate2012-06-29en_US
dc.date.rdate2016-09-27
dc.date.adate2012-08-09en_US


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