Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada
Jennifer A. Bako
Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada
J. Beatrice Liston
Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada
Huaxu Yu
Department of Chemistry, Faculty of Science, University of British Columbia, Vancouver, BC, Canada
Lianna W. Wat
Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada
Colin J. Miller
Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada
Michael D. Gordon
Department of Zoology, Life Sciences Institute, and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
Tao Huan
Department of Chemistry, Faculty of Science, University of British Columbia, Vancouver, BC, Canada
Molly Stanley
Department of Biology, University of Vermont, Burlington, VT, USA
Elizabeth J. Rideout
Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada; Corresponding author
Summary: In Drosophila, adult females store more fat than males. While the mechanisms that restrict body fat in males are becoming clearer, less is known about how females achieve higher fat storage. Here, we perform a detailed investigation of the mechanisms that promote higher fat storage in females. We show that a greater intake of dietary sugar supports higher fat storage due to female-biased remodeling of the fat body lipidome. Dietary sugar stimulates a female-specific increase in Drosophila insulin-like peptide 3 (Dilp3), which acts together with greater peripheral insulin sensitivity to augment insulin/insulin-like growth factor signaling pathway (IIS) activity in adult females. Indeed, Dilp3 overexpression prevented the female-biased decrease in body fat after removal of dietary sugar. Given that adult-specific IIS inhibition caused a female-biased decrease in body fat, our data reveal IIS as a key determinant of female fat storage.