The relationship between immunity and metabolism in Drosophila diet-induced
insulin resistance.
Authors Musselman LP, Fink JL, Grant AR, Gatto JA, Tuthill BF, Baranski TJ
Submitted By Laura Musselman on 11/1/2017
Status Published
Journal Molecular and cellular biology
Year 2017
Date Published 10/30/2017
Volume : Pages Not Specified : Not Specified
PubMed Reference 29084810
Abstract Systemic 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 using 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, 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.


Investigators with authorship
NameInstitution
Laura MusselmanSUNY at Binghamton

Complications