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Sayrany, Melody

University of British Columbia

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 mitochondrial biogenesis genes with glutamine, such results indicate that glutamine supplementation is probably harmful for the liver at an advanced age with existing metabolic defects but might be neutral or beneficial in healthier phenotypes. Overall, these results contribute to understanding the relationships between glutamine, lipid metabolism, and aging in middle-aged mouse livers.

Text

2022-06-07

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/81707

Biology

University of British Columbia

UBCO

http://creativecommons.org/licenses/by-nc-nd/4.0/