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Biswas, Puja

University of British Columbia

In most animals, females store more body fat than males. While catabolic factors have recently been shown to regulate the sex difference in body fat by restricting male fat storage, less is known about the metabolic pathways that promote fat storage in females. The objective of my PhD research was to determine the mechanisms by which adult females store more body fat than males, using Drosophila melanogaster as a model to study fat metabolism. In Chapter 2, my detailed examination of fat storage in both sexes revealed that increased food intake, specifically dietary sugar, supported higher fat storage in females. To identify the pathways that mediated these sex-biased effects, I performed a detailed investigation of the insulin/insulin-like growth factor signaling pathway (IIS), a pathway that regulates body fat, in male and female adult flies. I found mRNA levels of Drosophila insulin-like peptides (Ilps) were higher in females, and that females had higher peripheral insulin sensitivity. IIS activity in abdominal carcasses was also higher in females than in males. To test whether increased IIS activity contributed to higher fat storage in female flies, I ablated the insulin-producing cells (IPCs) specifically in adult flies and measured body fat. IPC ablation significantly reduced body fat in females but not in males. Together, my data suggest that IIS activity is higher in females, and this elevated activity contributes to the sex difference in body fat by promoting fat accumulation in females. In Chapter 3, I found that females had higher mRNA levels of gut hormones, and that genetic ablation of gut hormones decreased female body fat. Specifically, Allatostatin C and Tachykinin showed female-specific effects on fat storage. Together, my data reveal a previously unrecognized role for gut hormones in regulating the sex difference in body fat by promoting female-specific fat accumulation. In Chapter 4, I identified several methodological considerations for studying sex differences in fat metabolism in flies. Overall, my data provide important clues into the molecular and cellular mechanisms underlying the sex difference in fat storage and give insight into the sex-biased incidence of diseases associated with abnormal fat storage in mammals.

Text

2025-06-26

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/91447

Cell and Developmental Biology

University of British Columbia

UBCV

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