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Ablation of insulin-producing cells prevents obesity but not premature mortality caused by a high-sugar diet in Drosophila

Al Saud, SN; Summerfield, AC; Alic, N; (2015) Ablation of insulin-producing cells prevents obesity but not premature mortality caused by a high-sugar diet in Drosophila. Proc Biol Sci , 282 (1800) , Article 20141720. 10.1098/rspb.2014.1720. Green open access

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Abstract

Ageing can be modulated by genetic as well as nutritional interventions. In female Drosophila melanogaster, lifespan is maximized at intermediate concentrations of sucrose as the carbohydrate source, and yeast as the protein source. Dampening the signal through the insulin/IGF signalling (IIS) pathway, by genetic ablation of median neurosecretory cells (mNSCs) that produce insulin-like peptides, extends lifespan and counteracts the detrimental effects of excess yeast. However, how IIS reduction impacts health on a high-sugar diet remains unclear. We find that, while the ablation of the mNSCs can extend lifespan and delay the age-related decline in the health of the neuromuscular system irrespective of the amount of dietary sugar, it cannot rescue the lifespan-shortening effects of excess sugar. On the other hand, ablation of mNSCs can prevent adult obesity resulting from excess sugar, and this effect appears independent from the canonical effector of IIS, dfoxo. Our study indicates that while treatments that reduce IIS have anti-ageing effects irrespective of dietary sugar, additional interventions may be required to achieve full benefits in humans, where excessive sugar consumption is a growing problem. At the same time, pathways regulated by IIS may be suitable targets for treatment of obesity.

Type: Article
Title: Ablation of insulin-producing cells prevents obesity but not premature mortality caused by a high-sugar diet in Drosophila
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1098/rspb.2014.1720
Publisher version: http://dx.doi.org/10.1098/rspb.2014.1720
Language: English
Additional information: © 2014 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
Keywords: Drosophila melanogaster, ageing, high-sugar diet, insulin/IGF-like signalling, obesity
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/1459799
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