A Complex Relationship between Immunity and Metabolism in Drosophila Diet-Induced Insulin Resistance.

Autor:	Musselman LP; Binghamton University, Department of Biological Sciences, Binghamton, New York, USA lmusselm@binghamton.edu.; Washington University School of Medicine, Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, St. Louis, Missouri, USA., Fink JL; Washington University School of Medicine, Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, St. Louis, Missouri, USA., Grant AR; Bioinformatics Core, University of Michigan, Ann Arbor, Michigan, USA., Gatto JA; Binghamton University, Department of Biological Sciences, Binghamton, New York, USA., Tuthill BF 2nd; Binghamton University, Department of Biological Sciences, Binghamton, New York, USA., Baranski TJ; Washington University School of Medicine, Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, St. Louis, Missouri, USA.
Jazyk:	angličtina
Zdroj:	Molecular and cellular biology [Mol Cell Biol] 2017 Dec 29; Vol. 38 (2). Date of Electronic Publication: 2017 Dec 29 (Print Publication: 2018).
DOI:	10.1128/MCB.00259-17
Abstrakt:	Both systemic insulin resistance and tissue-specific insulin resistance have been described in Drosophila and are accompanied by many indicators of metabolic disease. The downstream mediators of insulin-resistant pathophysiology remain unclear. We analyzed insulin signaling in the fat body studying loss and gain of function. When expression of the sole Drosophila insulin receptor (InR) was reduced in larval fat bodies, animals exhibited developmental delay and reduced size in a diet-dependent manner. Fat body InR knockdown also led to reduced survival on high-sugar diets. To look downstream of InR at potential mediators of insulin resistance, transcriptome sequencing (RNA-seq) studies in insulin-resistant fat bodies revealed differential expression of genes, including those involved in innate immunity. Obesity-associated insulin resistance led to increased susceptibility of flies to infection, as in humans. Reduced innate immunity was dependent on fat body InR expression. The peptidoglycan recognition proteins (PGRPs) PGRP-SB2 and PGRP-SC2 were selected for further study based on differential expression studies. Downregulating PGRP-SB2 selectively in the fat body protected animals from the deleterious effects of overnutrition, whereas downregulating PGRP-SC2 produced InR-like phenotypes. These studies extend earlier work linking the immune and insulin signaling pathways and identify new targets of insulin signaling that could serve as potential drug targets to treat type 2 diabetes. (Copyright © 2017 American Society for Microbiology.)
Databáze:	MEDLINE
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