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

Broughton, Susan and Alic, Nazif and Slack, Cathy and Bass, Timothy and Ikeya, Tomoatsu and Vinti, Giovanna and Tommasi, Anna Maria and Driege, Yasmine and 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). ISSN 1932-6203

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    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 dInR, 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.

    Item Type: Article
    Journal or Publication Title: PLoS ONE
    Uncontrolled Keywords: Insulin/IGF-like signalling ; Ageing ; Drosophila ; DILP ; Gene Expression Regulation ; Glycogen ; Lipid Metabolism ; Longevity ; Oxidative Stress ; Trehalose
    Subjects: R Medicine > R Medicine (General)
    Departments: Faculty of Health and Medicine > Biomedical & Life Sciences
    ID Code: 49885
    Deposited By: ep_importer_pure
    Deposited On: 20 Sep 2011 10:27
    Refereed?: Yes
    Published?: Published
    Last Modified: 27 Feb 2014 14:47
    Identification Number:
    URI: http://eprints.lancs.ac.uk/id/eprint/49885

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