The Implications of CD36 Alteration on Rodent Skeletal Muscle Lipid Metabolism

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dc.contributor.advisorBonen, Arend
dc.contributor.authorLally, James
dc.date.accessioned2012-09-13T13:40:59Z
dc.date.available2012-09-13T13:40:59Z
dc.date.copyright2012-06
dc.date.created2012-05-18
dc.date.issued2012-09-13
dc.degree.departmentDepartment of Human Health and Nutritional Sciencesen_US
dc.degree.grantorUniversity of Guelphen_US
dc.degree.nameDoctor of Philosophyen_US
dc.degree.programmeHuman Health and Nutritional Sciencesen_US
dc.description.abstractFatty acid transport across the plasma membrane is an important site of regulation in skeletal muscle lipid metabolism, and is governed by a number of fatty acid transport proteins including, CD36, FABPpm, and FATP1 and 4. While each transporter is capable of independently stimulating fatty acid transport, less is known about their specific functions under various metabolic conditions, although CD36 appears to be key. The purpose of this thesis was to examine skeletal muscle fatty acid metabolism in several rodent models where CD36 has been altered, particularly via whole body deletion, by muscle specific overexpression, or in the face of permanent redistribution of CD36 to the plasma membrane. Using these models, this thesis sought to answer the following questions: 1) Is caffeine-stimulated fatty acid oxidation CD36-dependent? 2) Does CD36 function in tandem with FABPpm, and does this enhance fatty acid uptake at the plasma membrane and/or influence the metabolic fate of incoming fatty acids? 3) Is intramuscular lipid distribution altered in a rodent model of obesity, in which CD36-mediated fatty acid uptake is increased? Specific novel findings include the following: 1) Caffeine-stimulated calcium release can elicit the translocation of a number of fatty acid transporters in skeletal muscle, but CD36 is essential for caffeine-induced increases in fatty acid uptake and oxidation. 2) In spite of difficulties associated with protein co-overexpression, it appears that simultaneous overexpression of CD36 and FABPpm enhances fatty acid transport across the plasma membrane, and that these transporters may collaborate to increase insulin-induced fatty acid esterification and AICAR-induced oxidation. 3) Finally, in the obese Zucker rat model, augmented CD36-dependent fatty acid transport into muscle in combination with elevated lipid supply, results in lipid accretion within the IMF region of muscle, an effect that could not be explained by compartment-specific changes in selected glycerolipid synthesizing enzymes. Taken together, these studies emphasize the importance of CD36 in the regulation of plasmalemmal fatty acid transport, and further elucidate the metabolic implication of CD36 alteration on overall skeletal muscle metabolism.en_US
dc.identifier.urihttp://hdl.handle.net/10214/3979
dc.language.isoenen_US
dc.publisherUniversity of Guelphen_US
dc.rights.licenseAll items in the Atrium are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectskeletalen_US
dc.subjectmuscleen_US
dc.subjectfattyen_US
dc.subjectaciden_US
dc.subjectmetabolismen_US
dc.titleThe Implications of CD36 Alteration on Rodent Skeletal Muscle Lipid Metabolismen_US
dc.typeThesisen_US
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