Reduction of DILP2 in Drosophila triages a metabolic phenotype from lifespan revealing redundancy and compensation among DILPs

Broughton, Susan, Alic, Nazif, Slack, Cathy, Bass, Timothy, Ikeya, Tomoatsu, Vinti, Giovanna, Tommasi, Anna Maria, Driege, Yasmine, Hafen, Ernst and Partridge, Linda (2008). Reduction of DILP2 in Drosophila triages a metabolic phenotype from lifespan revealing redundancy and compensation among DILPs. PLoS ONE, 3 (11),

Abstract

The insulin/IGF-like signalling (IIS) pathway has diverse functions in all multicellular organisms, including determination of lifespan. The seven insulin-like peptides (DILPs) in Drosophila are expressed in a stage- and tissue-specific manner. Partial ablation of the median neurosecretory cells (mNSCs) in the brain, which produce three DILPs, extends lifespan, reduces fecundity, alters lipid and carbohydrate metabolism and increases oxidative stress resistance. To determine if reduced expression of DILPs is causal in these effects, and to investigate possible functional diversification and redundancy between DILPs, we used RNA interference to lower specifically the transcript and protein levels of dilp2, the most highly expressed of the mNSC-derived DILPs. We found that DILP2 was limiting only for the increased whole-body trehalose content associated with mNSC-ablation. We observed a compensatory increase in dilp3 and 5 mRNA upon dilp2 knock down. By manipulation of dfoxo and dlnR, we showed that the increase in dilp3 is regulated via autocrine insulin signaling in the mNSCs. Our study demonstrates that, despite the correlation between reduced dilp2 mRNA levels and lifespan-extension often observed, DILP2 reduction is not sufficient to extend lifespan. Nor is the increased trehalose storage associated with reduced IIS sufficient to extend lifespan. To understand the normal regulation of expression of the dilps and any functional diversification between them will require independent control of the expression of different dilps.

Publication DOI: https://doi.org/10.1371/journal.pone.0003721
Divisions: Life & Health Sciences
Additional Information: © 2008 Broughton et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Uncontrolled Keywords: Agricultural and Biological Sciences(all),Biochemistry, Genetics and Molecular Biology(all),Medicine(all)
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Related URLs: http://www.scopus.com/inward/record.url?scp=56649121807&partnerID=8YFLogxK (Scopus URL)
Published Date: 2008-11-13
Authors: Broughton, Susan
Alic, Nazif
Slack, Cathy ( 0000-0002-7949-4079)
Bass, Timothy
Ikeya, Tomoatsu
Vinti, Giovanna
Tommasi, Anna Maria
Driege, Yasmine
Hafen, Ernst
Partridge, Linda

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