Bettedi, L;
Yan, A;
Schuster, E;
Alic, N;
Foukas, LC;
(2020)
Increased mitochondrial and lipid metabolism is a conserved effect of Insulin/PI3K pathway downregulation in adipose tissue.
Scientific Reports
, 10
, Article 3418. 10.1038/s41598-020-60210-3.
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Abstract
The Insulin/IGF-1 signalling (IIS) pathway plays an essential role in the regulation of glucose and lipid homeostasis. At the same time, a reduction in the IIS pathway activity can extend lifespan and healthspan in various model organisms. Amongst a number of body organs that sense and respond to insulin/IGF-1, the adipose tissue has a central role in both the metabolic and lifespan efects of IIS at the organismal level. Genetic inactivation of IIS components specifcally in the adipose tissue has been shown before to improve metabolic profle and extend lifespan in various model organisms. We sought to identify conserved molecular mechanisms that may underlie the benefcial efects of IIS inhibition in the adipose tissue, specifcally at the level of phosphoinositide 3-kinase (PI3K), a key IIS efector molecule. To this end, we inactivated PI3K by genetic means in the fy fat body and by pharmacological inhibition in mammalian adipocytes. Gene expression studies revealed changes to metabolism and upregulation of mitochondrial activity in mouse adipocytes and fy fat bodies with downregulated PI3K, which were confrmed by biochemical assays in mammalian adipocytes. These data suggest that PI3K inactivation has a conserved efect of upregulating mitochondrial metabolism in both fy and mammalian adipose tissue, which likely contributes to the health- and life-span extending efect of IIS pathway downregulation.
| Type: | Article |
|---|---|
| Title: | Increased mitochondrial and lipid metabolism is a conserved effect of Insulin/PI3K pathway downregulation in adipose tissue |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41598-020-60210-3 |
| Publisher version: | http://dx.doi.org/10.1038/s41598-020-60210-3 |
| Language: | English |
| Additional information: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| UCL classification: | UCL 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/10092725 |
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