The Role of Adipose HIF1a in Drosophila Hypoxia Tolerance
AdvisorGrewal, Savraj S.
Committee MemberShutt, Timothy E.
Brook, William J.
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AbstractAnimals often develop and live in environments where environmental factors are constantly fluctuating. One of these factors is oxygen, and low oxygen, or hypoxia, is quite harmful to most animals. However, some have developed mechanisms that allow them to alter their physiology and metabolism in order to survive these hypoxic conditions. Drosophila are one such animal, making them an ideal model organism for hypoxia research. In this study, I examined the role of the transcription factor HIF-1α/ Sima in adult hypoxia tolerance in Drosophila. I found that Sima expression in the fat body controls the systemic response to hypoxia. The systemic effects are exerted independently of insulin signaling. Instead, my findings suggest that a key role of fat body Sima is to restrict the induction of the IMD and JAK/STAT signaling in hypoxia, two pathways involved in the Drosophila immune response. Further, I found that over activating the JAK/STAT pathway decreased hypoxia survival. Additionally, I found that fat body Sima plays a role in metabolic alterations that are likely important for hypoxia tolerance. I found that adults accumulate lipid stores in hypoxia and these lipid stores are even further increased in Sima knockdown adults. Therefore, Sima in the fat body has a role in properly regulating lipid metabolism. Fat body Sima knockdown impacted the level of glycogen and glycogen metabolism genes in normoxia, suggesting that Sima also has important roles in controlling metabolism at basal levels Overall, these results increase our understanding of the mechanisms underlying hypoxia tolerance in Drosophila adults, emphasizing the importance of the fat body in the non-autonomous response. Sima/ HIF-1α, as well as the immune and cytokine pathways I found it to regulate are conserved in humans. Additionally, adipose tissue often becomes hypoxic, leading to HIF-1α accumulation in obesity. Several other diseases are also associated with hypoxia and HIF-1α, making my findings relevant to our understanding of human disease.
CitationPolan, D. (2021). The Role of Adipose HIF1a in Drosophila Hypoxia Tolerance (Unpublished master's thesis). University of Calgary, Calgary, AB.
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