Seven-Up Is a Novel Regulator of Insulin Signaling

Genetics: A Periodical Record of Investigations Bearing on Heredity and Variation

Jill L. Fink^2¹  Michael R. Brent^5²  Thomas J. Baranski^2³  Jared A. Gatto^4⁴  Laura Palanker Musselman^1⁵  Ezekiel J. Maier^3⁶ 

[1] Department of Biological Sciences, Binghamton University, New York 13902^1;Department of Biological Sciences, Binghamton University, New York 13902^4;Department of Computer Science, Washington University in St. Louis, Missouri 63110^5;Department of Computer Science, and Department of Genetics and^3;Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110;Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110^2

关键词: Drosophila;    diabetes;    obesity;    Seven-up;    ecdysone receptor;   

DOI  :  10.1534/genetics.118.300770

学科分类：医学（综合）

来源: Genetics Society of America

【 摘 要 】

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.

【 授权许可】

CC BY