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

Molecular and Cellular Biology
Laura Palanker MusselmanThomas J Baranski

Abstract

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, ...Continue Reading

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Citations

Jun 30, 2018·International Journal of Molecular Sciences·Martina Gáliková, Peter Klepsatel
Feb 20, 2019·FEBS Letters·Pinreddy KarunakarAbhay Sharma
Mar 27, 2019·Disease Models & Mechanisms·Jessica SharrockMarc S Dionne
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Mar 1, 2018·Genetics·Laura Palanker MusselmanThomas J Baranski
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