Doctor of Philosophy in Cell and Developmental Biology (PhD)
Understanding how females and males store and metabolize fat differently
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Sexual size dimorphism (SSD) is common throughout the animal kingdom. Inthe fruit fly, Drosophila melanogaster, females are ~30% larger than males. Over thepast two decades, studies in Drosophila have expanded our knowledge of thegenetic and dietary requirements for growth. However, it remains incompletelyunderstood how males and females differ in the regulation of growth. Theinsulin/insulin-like growth factor signaling pathway (IIS) was found to be a keyregulator of nutrient-dependent growth and body size. The appropriate coupling ofgrowth with dietary nutrients is known as body size plasticity. Recent studies haveimplicated both dietary nutrients and IIS in establishing SSD, but the mechanismremains poorly understood. To better understand how males and females differ ingrowth, I used Drosophila to perform a series of studies examining the contributionof nutrients and IIS on growth in both sexes.In Chapter 2, I found that IIS activity is required for increased female bodysize. Further, genetically augmenting IIS in males is sufficient for increased bodysize. In Chapter 3, I build upon this characterization and identify that in a high proteindietary context, females increase IIS activity and body size more than males. Thisresults in increased female body size plasticity. Specifically, when dietary protein isabundant, females produce high levels of the insulinotropic factor Stunted whichpromotes increased IIS and larger body size. This mechanism was dependent onthe sex determination gene transformer. These findings elucidate a molecularmechanism underlying the sex difference in body size plasticity. In Chapter 4, Ipresent evidence that in a low-sugar dietary context both sexes increase growth viadistinct mechanisms to achieve the same phenotype. Specifically, males increaseIIS activity whereas females increase target of rapamycin (TOR) signaling to reach alarger body size. Together, my thesis provides novel mechanistic insight into howmales and females differ in their phenotypic response to genetic manipulation anddietary manipulation. This work provides the basis for future studies to identifyconserved sex differences in the regulation of nutrient-responsive pathways, andultimately will inform our knowledge of the sex-biased risk of human metabolicdisease.