The role of glutamine homeostasis in the middle-aged liver
department or school: Science, Irving K. Barber Faculty of (Okanagan)
department or school: Biology, Department of (Okanagan)
data provider: DSpace
degree campus: UBCO
creator: Sayrany, Melody
issued: 2022-06-07T16:55:17Z
issued: 2022
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Age-related diseases encompass confounding biological insults, some of which are related to dysregulated amino acid and lipid metabolism. Glutamine is one of the most abundant and vital amino acid for cellular processes that is depleted during conditions of stress and aging. Besides glutamine, polyunsaturated fatty acid (PUFA) metabolism is also altered in aging. However, their inter-relationship in the context of the liver is unknown. My project was to investigate the effects of glutamine supplementation and lipid metabolism in middle-aged mouse livers. To this end, we selected a mouse deficient in fatty acid elongase 5 (Elovl5), with impaired PUFA bioconversion and another mouse deficient in endonuclease G (EndoG), which stays protected in aging due to a lack of endonuclease activity and attenuation of mitochondrial DNA breakdown. My first objective was to identify said relationship in middle-aged livers of Elovl5 and EndoG heterozygous mice by feeding glutamine or alanine, while keeping C57/Bl6 mice (wild type, WT) as controls (Chapter 2). We show that glutamine supplementation does not affect gene expressions of glutamine-related metabolic (glutaminase 2, glutamine synthase, and glutamine dehydrogenase), or PUFA bioconversion (fatty acid desaturase 1/2 and Elovl5), enzymes in WT, and they were decreased in EndoG+/- mice livers. In contrast, glutamine supplemented Elovl5+/- mice livers showed upregulated gene expressions for both. For my second objective in Chapter 3, we determined the impact of glutamine or alanine on inflammation and mitochondrial biogenesis markers in the same livers. Glutamine-fed WT mice demonstrated no change while EndoG+/- showed a decrease in gene expressions of pro-inflammatory or mitochondrial biogenesis markers. Elovl5+/- mice on the other hand, demonstrated increased gene expression both inflammation and mitochondrial biogenesis markers. Given the fact that Elovl5+/- livers had increased levels of lipogenic as well as inflammatory and…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/81707
note: i THE ROLE OF GLUTAMINE HOMEOSTASIS IN THE MIDDLE-AGED LIVER by Melody Sayrany B.Sc., University of California San Diego, 2016 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE COLLEGE OF GRADUATE STUDIES (Biology) THE UNIVERSITY OF BRITISH COLUMBIA (Okanagan) May 2022 © Melody Sayrany, 2022 i The following individuals certify that they have read, and recommend to the College of Graduate Studies for acceptance, a thesis/dissertation entitled: The Role of Glutamine Homeostasis in the Middle-Aged Liver submitted by Melody Sayrany in partial fulfillment of the requirements for the degree of Master of Science. Dr. Sanjoy Ghosh, Faculty of Science Supervisor Dr. Rajavel Elango, Faculty of Medicine Supervisory Committee Member Dr. Christopher West, Faculty of Education Supervisory Committee Member Dr. Angela Devlin, Faculty of Medicine University Examiner ii Abstract Age-related diseases encompass confounding biological insults, some of which are related to dysregulated amino acid and lipid metabolism. Glutamine is one of the most abundant and vital amino acid for cellular processes that is depleted during conditions of stress and aging. Besides glutamine, polyunsaturated fatty acid (PUFA) metabolism is also altered in aging. However, their inter-relationship in the context of the liver is unknown. My project was to investigate the effects of glutamine supplementation and lipid metabolism in middle-aged mouse livers. To this end, we selected a mouse deficient in fatty acid elongase 5 (Elovl5), with impaired PUFA bioconversion and another mouse deficient in endonuclease G (EndoG), which stays protected in aging due to a lack of endonuclease activity and attenuation of mitochondrial DNA breakdown. My first objective was to identify said relationship in middle-aged livers of Elovl5 and EndoG heterozygous mice by feeding glutamine or alanine, while keeping C57/Bl6 mice (wild type, WT) as controls (Chapter 2). We show that…
has type: Thesis/Dissertation
date issued: 2022-09
is shown at: 10.14288/1.0413785
language: eng
degree discipline: Biology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Ghosh, Sanjoy
type: Text
identifier URI: http://hdl.handle.net/2429/81707