Seven-Up Is a Novel Regulator of Insulin Signaling

Genetics
Laura Palanker MusselmanThomas J Baranski

Abstract

Insulin resistance is associated with obesity, cardiovascular disease, non-alcoholic fatty liver disease, and type 2 diabetes. These complications are exacerbated by a high-calorie diet, which we used to model type 2 diabetes in Drosophila melanogaster Our studies focused on the fat body, an adipose- and liver-like tissue that stores fat and maintains circulating glucose. A gene regulatory network was constructed to predict potential regulators of insulin signaling in this tissue. Genomic characterization of fat bodies suggested a central role for the transcription factor Seven-up (Svp). Here, we describe a new role for Svp as a positive regulator of insulin signaling. Tissue-specific loss-of-function showed that Svp is required in the fat body to promote glucose clearance, lipid turnover, and insulin signaling. Svp appears to promote insulin signaling, at least in part, by inhibiting ecdysone signaling. Svp also impairs the immune response possibly via inhibition of antimicrobial peptide expression in the fat body. Taken together, these studies show that gene regulatory networks can help identify positive regulators of insulin signaling and metabolic homeostasis using the Drosophila fat body.

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Citations

Mar 27, 2019·Disease Models & Mechanisms·Jessica SharrockMarc S Dionne
Jan 12, 2020·Journal of Biochemistry·Howard T JacobsEsko Kemppainen
Apr 27, 2020·Archives of Insect Biochemistry and Physiology·Umut ToprakGözde Güney
May 28, 2020·Frontiers in Physiology·Umut Toprak
Oct 23, 2020·G3 : Genes - Genomes - Genetics·Lesley N Weaver, Daniela Drummond-Barbosa
Jul 30, 2021·Development·Scott A KeithBrooke M McCartney
Aug 24, 2021·The Journal of Experimental Biology·Bryon F Tuthill IiLaura Palanker Musselman

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