{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/129772"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/129772","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"The impact of alpha-tocopherol status on brain polyunsaturated fatty acid composition and oxidative stress","abstract":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2027-05-01","abstract_html":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2027-05-01","abstract_has_math":false,"creators":["Sutton, Harper"],"institution":"University of Illinois Urbana-Champaign","degree_name":"M.S.","degree_level":"Thesis","degree_discipline":"Food Science & Human Nutrition","degree_department":null,"school":null,"contributors":["Erdman, John W","Amengual, Jaume","Cadwallader, Keith R"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-05-06","date_published":"2025-05-06","updated_at":"2026-07-22T22:25:05Z","subjects":["Alpha-tocopherol","oxidative stress","polyunsaturated fatty acids","antioxidant"],"languages":["en","eng"],"rights":["Copyright 2025 Harper Sutton"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/129772","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Erdman, John W","Amengual, Jaume","Cadwallader, Keith R"]},{"key":"dc:creator","label":"Author","values":["Sutton, Harper"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-05-06","2025-05"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Food Science & Human Nutrition"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M.S."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Alpha-tocopherol","oxidative stress","polyunsaturated fatty acids","antioxidant"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en","eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2025 Harper Sutton"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/129772"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2027-05-01","The student, Harper Sutton, accepted the attached license on 2025-05-02 at 10:55.","The student, Harper Sutton, submitted this Thesis for approval on 2025-05-02 at 11:08.","This Thesis was approved for publication on 2025-05-06 at 16:28.","DSpace SAF Submission Ingestion Package generated from Vireo submission #22177 on 2025-10-19 at 19:55:41","α-Tocopherol (αT) is a lipophilic antioxidant that prevents lipid peroxidation by donating its phenolic hydrogen to peroxyl radicals. Its antioxidant capacity is particularly important for neurological functioning, and many studies have been conducted to evaluate the role of αT in neuroprotection and cognitive functioning. Polyunsaturated fatty acids (PUFAs) are highly abundant in the brain, and are especially susceptible to lipid peroxidation, which can cause significant damage to cell membranes and promote cell death. Lipid peroxidation in the nervous system is linked to neurodegenerative disease, cancer, and other neurological disorders. Adequate αT status is essential to prevent the propagation of lipid peroxidation and protect brain PUFAs. This thesis focuses on alpha tocopherol (αT) primarily due to its preferential incorporation into very low density lipoproteins (VLDL) for extrahepatic distribution by the αtocopherol transfer protein (α-TTP). α-TTP is expressed in the liver and brain, which suggests an essentiality of αT for proper functioning of the nervous system. We utilized the α-TTP knockout (Ttpa-/-) mouse model to study vitamin E deficiency. It is difficult to create vitamin E deficiency using wild-type mice, as vitamin E has a long half-life, making it challenging to deplete tissues, especially the brain. Ttpa-/- mice have very low tissue levels of αT (outside of the liver), which makes them a suitable model for extrahepatic vitamin E deficiency. This model has been well characterized in older mice, where oxidative stress and cognitive decline are common, however, the optimization of the model for younger mice is less developed. Previous work in this lab has explored the use of a lipopolysaccharide challenge to induce inflammation to assess oxidative stress in Ttpa-/- mice, as innate oxidative stress isn’t as ii abundant in younger mice. These studies have not yielded significant genotype differences in measures of oxidative stress and inflammation, which necessitates the exploration of additional endpoints related to oxidative stress to better characterize the model. This thesis primarily focuses on the impact of αT status on polyunsaturated fatty acid composition in the cerebral cortices of both Ttpa-/- and wild-type mice (Chapter 2). A secondary objective of this thesis is to determine the period of αT depletion necessary to observe significant reductions in brain PUFA concentrations compared to αT-sufficient mice. We hypothesized that mice fed an αT-deficient diet would have lower concentrations of PUFAs in the cerebral cortex compared to mice fed an αT-sufficient diet, and that these effects would be more pronounced in Ttpa-/- mice. We also anticipated that a longer period of αT deficiency would exacerbate these reductions in PUFA concentrations. Our research revealed that mice fed an αT-deficient diet had lower cortical PUFA concentrations compared to αT-sufficient mice, and that these effects were more pronounced after 12 weeks of αT depletion. Surprisingly, Ttpa-/- mice did not have lower PUFA levels compared to wild-type mice, and in fact, for some PUFAs, concentrations were lower for wild-type mice. Additional research is necessary to better understand the mechanisms by which αTdeficiency leads to a reduction in cortical PUFA concentrations, and also to explore the impact of supplementation following depletion on oxidative stress and brain PUFA composition. This work furthers our understanding of the Ttpa-/- mouse model and also αT’s role as an antioxidant."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["The impact of alpha-tocopherol status on brain polyunsaturated fatty acid composition and oxidative stress"]}]}],"canonical_facts":{"dc:contributor":["Erdman, John W","Amengual, Jaume","Cadwallader, Keith R"],"dc:creator":["Sutton, Harper"],"dc:date":["2025-05-06","2025-05"],"dc:description":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2027-05-01","The student, Harper Sutton, accepted the attached license on 2025-05-02 at 10:55.","The student, Harper Sutton, submitted this Thesis for approval on 2025-05-02 at 11:08.","This Thesis was approved for publication on 2025-05-06 at 16:28.","DSpace SAF Submission Ingestion Package generated from Vireo submission #22177 on 2025-10-19 at 19:55:41","α-Tocopherol (αT) is a lipophilic antioxidant that prevents lipid peroxidation by donating its phenolic hydrogen to peroxyl radicals. Its antioxidant capacity is particularly important for neurological functioning, and many studies have been conducted to evaluate the role of αT in neuroprotection and cognitive functioning. Polyunsaturated fatty acids (PUFAs) are highly abundant in the brain, and are especially susceptible to lipid peroxidation, which can cause significant damage to cell membranes and promote cell death. Lipid peroxidation in the nervous system is linked to neurodegenerative disease, cancer, and other neurological disorders. Adequate αT status is essential to prevent the propagation of lipid peroxidation and protect brain PUFAs. This thesis focuses on alpha tocopherol (αT) primarily due to its preferential incorporation into very low density lipoproteins (VLDL) for extrahepatic distribution by the αtocopherol transfer protein (α-TTP). α-TTP is expressed in the liver and brain, which suggests an essentiality of αT for proper functioning of the nervous system. We utilized the α-TTP knockout (Ttpa-/-) mouse model to study vitamin E deficiency. It is difficult to create vitamin E deficiency using wild-type mice, as vitamin E has a long half-life, making it challenging to deplete tissues, especially the brain. Ttpa-/- mice have very low tissue levels of αT (outside of the liver), which makes them a suitable model for extrahepatic vitamin E deficiency. This model has been well characterized in older mice, where oxidative stress and cognitive decline are common, however, the optimization of the model for younger mice is less developed. Previous work in this lab has explored the use of a lipopolysaccharide challenge to induce inflammation to assess oxidative stress in Ttpa-/- mice, as innate oxidative stress isn’t as ii abundant in younger mice. These studies have not yielded significant genotype differences in measures of oxidative stress and inflammation, which necessitates the exploration of additional endpoints related to oxidative stress to better characterize the model. This thesis primarily focuses on the impact of αT status on polyunsaturated fatty acid composition in the cerebral cortices of both Ttpa-/- and wild-type mice (Chapter 2). A secondary objective of this thesis is to determine the period of αT depletion necessary to observe significant reductions in brain PUFA concentrations compared to αT-sufficient mice. We hypothesized that mice fed an αT-deficient diet would have lower concentrations of PUFAs in the cerebral cortex compared to mice fed an αT-sufficient diet, and that these effects would be more pronounced in Ttpa-/- mice. We also anticipated that a longer period of αT deficiency would exacerbate these reductions in PUFA concentrations. Our research revealed that mice fed an αT-deficient diet had lower cortical PUFA concentrations compared to αT-sufficient mice, and that these effects were more pronounced after 12 weeks of αT depletion. Surprisingly, Ttpa-/- mice did not have lower PUFA levels compared to wild-type mice, and in fact, for some PUFAs, concentrations were lower for wild-type mice. Additional research is necessary to better understand the mechanisms by which αTdeficiency leads to a reduction in cortical PUFA concentrations, and also to explore the impact of supplementation following depletion on oxidative stress and brain PUFA composition. This work furthers our understanding of the Ttpa-/- mouse model and also αT’s role as an antioxidant."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/129772"],"dc:language":["en","eng"],"dc:rights":["Copyright 2025 Harper Sutton"],"dc:subject":["Alpha-tocopherol","oxidative stress","polyunsaturated fatty acids","antioxidant"],"dc:title":["The impact of alpha-tocopherol status on brain polyunsaturated fatty acid composition and oxidative stress"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Food Science & Human Nutrition"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["M.S."],"thesis:institution_name":["University of Illinois Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:05Z"}