Intestinal IRE1 Is Required for Increased Triglyceride Metabolism and Longer Lifespan under Dietary Restriction
Summary: Dietary restriction (DR) is one of the most robust lifespan-extending interventions in animals. The beneficial effects of DR involve a metabolic adaptation toward increased triglyceride usage. The regulatory mechanism and the tissue specificity of this metabolic switch remain unclear. Here,...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2016-10-01
|
Series: | Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716313729 |
id |
doaj-850a4592519a472ea7bcebdedee532ec |
---|---|
record_format |
Article |
spelling |
doaj-850a4592519a472ea7bcebdedee532ec2020-11-25T00:27:31ZengElsevierCell Reports2211-12472016-10-0117512071216Intestinal IRE1 Is Required for Increased Triglyceride Metabolism and Longer Lifespan under Dietary RestrictionNuno Miguel Luis0Lifen Wang1Mauricio Ortega2Hansong Deng3Subhash D. Katewa4Patrick Wai-Lun Li5Jason Karpac6Heinrich Jasper7Pankaj Kapahi8Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA; Corresponding authorBuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USABuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USABuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USABuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USABuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USADepartment of Molecular and Cellular Medicine, Texas A&M Health Science Center, College Station, TX 77843, USABuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA; Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena 07745, Germany; Corresponding authorBuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA; Corresponding authorSummary: Dietary restriction (DR) is one of the most robust lifespan-extending interventions in animals. The beneficial effects of DR involve a metabolic adaptation toward increased triglyceride usage. The regulatory mechanism and the tissue specificity of this metabolic switch remain unclear. Here, we show that the IRE1/XBP1 endoplasmic reticulum (ER) stress signaling module mediates metabolic adaptation upon DR in flies by promoting triglyceride synthesis and accumulation in enterocytes (ECs) of the Drosophila midgut. Consistently, IRE1/XBP1 function in ECs is required for increased longevity upon DR. We further identify sugarbabe, a Gli-like zinc-finger transcription factor, as a key mediator of the IRE1/XBP1-regulated induction of de novo lipogenesis in ECs. Overexpression of sugarbabe rescues metabolic and lifespan phenotypes of IRE1 loss-of-function conditions. Our study highlights the critical role of metabolic adaptation of the intestinal epithelium for DR-induced lifespan extension and explores the IRE1/XBP1 signaling pathway regulating this adaptation and influencing lifespan. : A metabolic switch that enhances triglyceride utilization mediates the protective effects of dietary restriction (DR), which extends the health span in multiple species. Luis et al. find that intestinal cells respond to DR by increasing lipid synthesis via the IRE1/XBP1/sugarbabe signaling module, thus extending longevity in Drosophila. Keywords: dietary restriction, aging, IRE1, metabolic adaptation, lipid turnover, longevity, Drosophilahttp://www.sciencedirect.com/science/article/pii/S2211124716313729 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nuno Miguel Luis Lifen Wang Mauricio Ortega Hansong Deng Subhash D. Katewa Patrick Wai-Lun Li Jason Karpac Heinrich Jasper Pankaj Kapahi |
spellingShingle |
Nuno Miguel Luis Lifen Wang Mauricio Ortega Hansong Deng Subhash D. Katewa Patrick Wai-Lun Li Jason Karpac Heinrich Jasper Pankaj Kapahi Intestinal IRE1 Is Required for Increased Triglyceride Metabolism and Longer Lifespan under Dietary Restriction Cell Reports |
author_facet |
Nuno Miguel Luis Lifen Wang Mauricio Ortega Hansong Deng Subhash D. Katewa Patrick Wai-Lun Li Jason Karpac Heinrich Jasper Pankaj Kapahi |
author_sort |
Nuno Miguel Luis |
title |
Intestinal IRE1 Is Required for Increased Triglyceride Metabolism and Longer Lifespan under Dietary Restriction |
title_short |
Intestinal IRE1 Is Required for Increased Triglyceride Metabolism and Longer Lifespan under Dietary Restriction |
title_full |
Intestinal IRE1 Is Required for Increased Triglyceride Metabolism and Longer Lifespan under Dietary Restriction |
title_fullStr |
Intestinal IRE1 Is Required for Increased Triglyceride Metabolism and Longer Lifespan under Dietary Restriction |
title_full_unstemmed |
Intestinal IRE1 Is Required for Increased Triglyceride Metabolism and Longer Lifespan under Dietary Restriction |
title_sort |
intestinal ire1 is required for increased triglyceride metabolism and longer lifespan under dietary restriction |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2016-10-01 |
description |
Summary: Dietary restriction (DR) is one of the most robust lifespan-extending interventions in animals. The beneficial effects of DR involve a metabolic adaptation toward increased triglyceride usage. The regulatory mechanism and the tissue specificity of this metabolic switch remain unclear. Here, we show that the IRE1/XBP1 endoplasmic reticulum (ER) stress signaling module mediates metabolic adaptation upon DR in flies by promoting triglyceride synthesis and accumulation in enterocytes (ECs) of the Drosophila midgut. Consistently, IRE1/XBP1 function in ECs is required for increased longevity upon DR. We further identify sugarbabe, a Gli-like zinc-finger transcription factor, as a key mediator of the IRE1/XBP1-regulated induction of de novo lipogenesis in ECs. Overexpression of sugarbabe rescues metabolic and lifespan phenotypes of IRE1 loss-of-function conditions. Our study highlights the critical role of metabolic adaptation of the intestinal epithelium for DR-induced lifespan extension and explores the IRE1/XBP1 signaling pathway regulating this adaptation and influencing lifespan. : A metabolic switch that enhances triglyceride utilization mediates the protective effects of dietary restriction (DR), which extends the health span in multiple species. Luis et al. find that intestinal cells respond to DR by increasing lipid synthesis via the IRE1/XBP1/sugarbabe signaling module, thus extending longevity in Drosophila. Keywords: dietary restriction, aging, IRE1, metabolic adaptation, lipid turnover, longevity, Drosophila |
url |
http://www.sciencedirect.com/science/article/pii/S2211124716313729 |
work_keys_str_mv |
AT nunomiguelluis intestinalire1isrequiredforincreasedtriglyceridemetabolismandlongerlifespanunderdietaryrestriction AT lifenwang intestinalire1isrequiredforincreasedtriglyceridemetabolismandlongerlifespanunderdietaryrestriction AT mauricioortega intestinalire1isrequiredforincreasedtriglyceridemetabolismandlongerlifespanunderdietaryrestriction AT hansongdeng intestinalire1isrequiredforincreasedtriglyceridemetabolismandlongerlifespanunderdietaryrestriction AT subhashdkatewa intestinalire1isrequiredforincreasedtriglyceridemetabolismandlongerlifespanunderdietaryrestriction AT patrickwailunli intestinalire1isrequiredforincreasedtriglyceridemetabolismandlongerlifespanunderdietaryrestriction AT jasonkarpac intestinalire1isrequiredforincreasedtriglyceridemetabolismandlongerlifespanunderdietaryrestriction AT heinrichjasper intestinalire1isrequiredforincreasedtriglyceridemetabolismandlongerlifespanunderdietaryrestriction AT pankajkapahi intestinalire1isrequiredforincreasedtriglyceridemetabolismandlongerlifespanunderdietaryrestriction |
_version_ |
1725339306348773376 |