Intestinal PPARγ signalling is required for sympathetic nervous system activation in response to caloric restriction

Nuclear receptor PPARγ has been proven to affect metabolism in multiple tissues, and has received considerable attention for its involvement in colon cancer and inflammatory disease. However, its role in intestinal metabolism has been largely ignored. To investigate this potential aspect of PPARγ fu...

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Main Authors: Duszka, Kalina, Picard, Alexandre, Ellero-Simatos, Sandrine, Chen, Jiapeng, Defernez, Marianne, Paramalingam, Eeswari, Pigram, Anna, Vanoaica, Liviu, Canlet, Cécile, Parini, Paolo, Narbad, Arjan, Guillou, Hervé, Thorens, Bernard, Wahli, Walter
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Journal Article
Language:English
Published: 2016
Subjects:
Online Access:https://hdl.handle.net/10356/84346
http://hdl.handle.net/10220/41789
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author Duszka, Kalina
Picard, Alexandre
Ellero-Simatos, Sandrine
Chen, Jiapeng
Defernez, Marianne
Paramalingam, Eeswari
Pigram, Anna
Vanoaica, Liviu
Canlet, Cécile
Parini, Paolo
Narbad, Arjan
Guillou, Hervé
Thorens, Bernard
Wahli, Walter
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Duszka, Kalina
Picard, Alexandre
Ellero-Simatos, Sandrine
Chen, Jiapeng
Defernez, Marianne
Paramalingam, Eeswari
Pigram, Anna
Vanoaica, Liviu
Canlet, Cécile
Parini, Paolo
Narbad, Arjan
Guillou, Hervé
Thorens, Bernard
Wahli, Walter
author_sort Duszka, Kalina
collection NTU
description Nuclear receptor PPARγ has been proven to affect metabolism in multiple tissues, and has received considerable attention for its involvement in colon cancer and inflammatory disease. However, its role in intestinal metabolism has been largely ignored. To investigate this potential aspect of PPARγ function, we submitted intestinal epithelium-specific PPARγ knockout mice (iePPARγKO) to a two-week period of 25% caloric restriction (CR), following which iePPARγKO mice retained more fat than their wild type littermates. In attempting to explain this discrepancy, we analysed the liver, skeletal muscle, intestinal lipid trafficking, and the microbiome, none of which appeared to contribute to the adiposity phenotype. Interestingly, under conditions of CR, iePPARγKO mice failed to activate their sympathetic nervous system (SNS) and increase CR-specific locomotor activity. These KO mice also manifested a defective control of their body temperature, which was overly reduced. Furthermore, the white adipose tissue of iePPARγKO CR mice showed lower levels of both hormone-sensitive lipase, and its phosphorylated form. This would result from impaired SNS signalling and possibly cause reduced lipolysis. We conclude that intestinal epithelium PPARγ plays an essential role in increasing SNS activity under CR conditions, thereby contributing to energy mobilization during metabolically stressful episodes.
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spelling ntu-10356/843462020-11-01T05:11:58Z Intestinal PPARγ signalling is required for sympathetic nervous system activation in response to caloric restriction Duszka, Kalina Picard, Alexandre Ellero-Simatos, Sandrine Chen, Jiapeng Defernez, Marianne Paramalingam, Eeswari Pigram, Anna Vanoaica, Liviu Canlet, Cécile Parini, Paolo Narbad, Arjan Guillou, Hervé Thorens, Bernard Wahli, Walter Lee Kong Chian School of Medicine (LKCMedicine) Lee Kong Chian School of Medicine Gene expression Metabolomics Nuclear receptor PPARγ has been proven to affect metabolism in multiple tissues, and has received considerable attention for its involvement in colon cancer and inflammatory disease. However, its role in intestinal metabolism has been largely ignored. To investigate this potential aspect of PPARγ function, we submitted intestinal epithelium-specific PPARγ knockout mice (iePPARγKO) to a two-week period of 25% caloric restriction (CR), following which iePPARγKO mice retained more fat than their wild type littermates. In attempting to explain this discrepancy, we analysed the liver, skeletal muscle, intestinal lipid trafficking, and the microbiome, none of which appeared to contribute to the adiposity phenotype. Interestingly, under conditions of CR, iePPARγKO mice failed to activate their sympathetic nervous system (SNS) and increase CR-specific locomotor activity. These KO mice also manifested a defective control of their body temperature, which was overly reduced. Furthermore, the white adipose tissue of iePPARγKO CR mice showed lower levels of both hormone-sensitive lipase, and its phosphorylated form. This would result from impaired SNS signalling and possibly cause reduced lipolysis. We conclude that intestinal epithelium PPARγ plays an essential role in increasing SNS activity under CR conditions, thereby contributing to energy mobilization during metabolically stressful episodes. Published version 2016-12-09T08:49:20Z 2019-12-06T15:43:14Z 2016-12-09T08:49:20Z 2019-12-06T15:43:14Z 2016 Journal Article Duszka, K., Picard, A., Ellero-Simatos, S., Chen, J., Defernez, M., Paramalingam, E., et al. (2016). Intestinal PPARγ signalling is required for sympathetic nervous system activation in response to caloric restriction. Scientific Reports, 6, 36937-. 2045-2322 https://hdl.handle.net/10356/84346 http://hdl.handle.net/10220/41789 10.1038/srep36937 en Scientific Reports © 2016 The Authors. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ 12 p. application/pdf
spellingShingle Gene expression
Metabolomics
Duszka, Kalina
Picard, Alexandre
Ellero-Simatos, Sandrine
Chen, Jiapeng
Defernez, Marianne
Paramalingam, Eeswari
Pigram, Anna
Vanoaica, Liviu
Canlet, Cécile
Parini, Paolo
Narbad, Arjan
Guillou, Hervé
Thorens, Bernard
Wahli, Walter
Intestinal PPARγ signalling is required for sympathetic nervous system activation in response to caloric restriction
title Intestinal PPARγ signalling is required for sympathetic nervous system activation in response to caloric restriction
title_full Intestinal PPARγ signalling is required for sympathetic nervous system activation in response to caloric restriction
title_fullStr Intestinal PPARγ signalling is required for sympathetic nervous system activation in response to caloric restriction
title_full_unstemmed Intestinal PPARγ signalling is required for sympathetic nervous system activation in response to caloric restriction
title_short Intestinal PPARγ signalling is required for sympathetic nervous system activation in response to caloric restriction
title_sort intestinal pparγ signalling is required for sympathetic nervous system activation in response to caloric restriction
topic Gene expression
Metabolomics
url https://hdl.handle.net/10356/84346
http://hdl.handle.net/10220/41789
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