Glucose supplementation impacts lifespan and immunity in Drosophila melanogaster

• Author / Creator

  Galenza, Anthony

• Interactions between diet, lifespan, metabolism, and immunity are complex but can have profound impact on human health. The Drosophila model is useful to study these interactions as many pathways and processes are highly conserved between flies and humans. In this thesis, I used the defined holidic diet to ask precisely how manipulation of a single nutrient affected aspects of health. I found that simple modifications to the defined holidic diet have a significant impact on Drosophila health, immunity, and lifespan. I found that glucose-supplemented holidic food extended median lifespan in male flies by 31%, but it also increased diversity in the intestinal microbiota composition. With antibiotic treatment, I found that glucose supplementation to the holidic diet extends lifespan independent of the intestinal microbiota. As glucose-supplemented food extended lifespan independent of the microbiota, I next sought the host-intrinsic mechanism of diet-dependent lifespan extension.
  Glucose-supplementation did not appear to extend lifespan through differences in caloric intake or altered insulin activity. Through RNA-Seq analysis, I found that glucose-supplemented food increased the expression of cell junction proteins. I used immunofluorescence to show that glucose supplementation increased localization of the septate junction protein, Coracle, to the junction by about 1.31-fold compared to the unmodified holidic food. Through a smurf assay, I found that flies raised on glucose-supplemented food had improved barrier function with age, and their lifespan advantage could be removed by chemically induced barrier disruption. Combined, I found that glucose-supplementation may extend lifespan through improved intestinal barrier integrity.
  Finally, I studied interactions between immunity and metabolism. I found that glucose-supplemented food improved survival to infection against V. cholerae. I also found that imd is required for metabolic homeostasis. Flies that lack imd have higher weight, glucose, and triglycerides. As well, imd flies have increased levels and slower clearance of glucose in a glucose tolerance test. Through RNA-Seq analysis, I found that imd may be involved in regulation of lipid metabolism. Combined, my major findings were that glucose supplementation may extend lifespan through regulation of the intestinal barrier and that the IMD pathway has a role in the metabolic regulation of lipids.

• Subjects / Keywords

  • Glucose
  • Drosophila melanogaster
  • Intestinal barrier
  • Immunometabolism

• Graduation date

  Fall 2020

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-vcpw-fj52

• License

  Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.