naa a22 4500 528783505 20180924065515.0 cr unu---uuuuu 180924e20081113xx s 000 0 eng 10.3929/ethz-b-000013726 doi 10.1371/journal.pone.0003721 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/13726 Reduction of DILP2 in Drosophila triages a metabolic phenotype from lifespan revealing redundancy and compensation among DILPs [Elektronische Daten] [Susan Broughton, Nazif Alic, Cathy Slack, Timothy Bass, Tomoatsu Ikeya, Giovanna Vinti, Anna Maria Tommasi, Yasmine Driege, Ernst Hafen, Linda Partridge] PLoS ONE Open access ethresearch 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. Creative Commons Attribution 3.0 Unported http://creativecommons.org/licenses/by/3.0 ethresearch Broughton Susan joint author Alic Nazif joint author Slack Cathy joint author Bass Timothy joint author Ikeya Tomoatsu joint author Vinti Giovanna joint author Tommasi Anna Maria joint author Driege Yasmine joint author Hafen Ernst joint author Partridge Linda joint author PLoS ONE [s.l.] : Public Library of Science 3 (11), p. e3721 1932-6203 http://hdl.handle.net/20.500.11850/13726 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/13726 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Broughton Susan joint author ETHRESEARCH 700 1- Alic Nazif joint author ETHRESEARCH 700 1- Slack Cathy joint author ETHRESEARCH 700 1- Bass Timothy joint author ETHRESEARCH 700 1- Ikeya Tomoatsu joint author ETHRESEARCH 700 1- Vinti Giovanna joint author ETHRESEARCH 700 1- Tommasi Anna Maria joint author ETHRESEARCH 700 1- Driege Yasmine joint author ETHRESEARCH 700 1- Hafen Ernst joint author ETHRESEARCH 700 1- Partridge Linda joint author ETHRESEARCH 773 0- PLoS ONE [s.l.] : Public Library of Science 3 (11), p. e3721 1932-6203 BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access