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Sirtuin 1 Regulates SREBP-1c Expression in a LXR-Dependent Manner in Skeletal Muscle

Sirtuin 1 (SIRT1), a NAD(+)-dependent protein deacetylase, has emerged as a main determinant of whole body homeostasis in mammals by regulating a large spectrum of transcriptional regulators in metabolically relevant tissue such as liver, adipose tissue and skeletal muscle. Sterol regulatory element...

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Autores principales: Defour, Aurélia, Dessalle, Kevin, Castro Perez, Andréa, Poyot, Thomas, Castells, Josiane, Gallot, Yann Simon, Durand, Christine, Euthine, Vanessa, Gu, Yansong, Béchet, Daniel, Peinnequin, André, Lefai, Etienne, Freyssenet, Damien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3439460/
https://www.ncbi.nlm.nih.gov/pubmed/22984430
http://dx.doi.org/10.1371/journal.pone.0043490
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author Defour, Aurélia
Dessalle, Kevin
Castro Perez, Andréa
Poyot, Thomas
Castells, Josiane
Gallot, Yann Simon
Durand, Christine
Euthine, Vanessa
Gu, Yansong
Béchet, Daniel
Peinnequin, André
Lefai, Etienne
Freyssenet, Damien
author_facet Defour, Aurélia
Dessalle, Kevin
Castro Perez, Andréa
Poyot, Thomas
Castells, Josiane
Gallot, Yann Simon
Durand, Christine
Euthine, Vanessa
Gu, Yansong
Béchet, Daniel
Peinnequin, André
Lefai, Etienne
Freyssenet, Damien
author_sort Defour, Aurélia
collection PubMed
description Sirtuin 1 (SIRT1), a NAD(+)-dependent protein deacetylase, has emerged as a main determinant of whole body homeostasis in mammals by regulating a large spectrum of transcriptional regulators in metabolically relevant tissue such as liver, adipose tissue and skeletal muscle. Sterol regulatory element binding protein (SREBP)-1c is a transcription factor that controls the expression of genes related to fatty acid and triglyceride synthesis in tissues with high lipid synthesis rates such as adipose tissue and liver. Previous studies indicate that SIRT1 can regulate the expression and function of SREBP-1c in liver. In the present study, we determined whether SIRT1 regulates SREBP-1c expression in skeletal muscle. SREBP-1c mRNA and protein levels were decreased in the gastrocnemius muscle of mice harboring deletion of the catalytic domain of SIRT1 (SIRT1(Δex4/Δex4) mice). By contrast, adenoviral expression of SIRT1 in human myotubes increased SREBP-1c mRNA and protein levels. Importantly, SREBP-1c promoter transactivation, which was significantly increased in response to SIRT1 overexpression by gene electrotransfer in skeletal muscle, was completely abolished when liver X receptor (LXR) response elements were deleted. Finally, our in vivo data from SIRT1(Δex4/Δex4) mice and in vitro data from human myotubes overexpressing SIRT1 show that SIRT1 regulates LXR acetylation in skeletal muscle cells. This suggests a possible mechanism by which the regulation of SREBP-1c gene expression by SIRT1 may require the deacetylation of LXR transcription factors.
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spelling pubmed-34394602012-09-14 Sirtuin 1 Regulates SREBP-1c Expression in a LXR-Dependent Manner in Skeletal Muscle Defour, Aurélia Dessalle, Kevin Castro Perez, Andréa Poyot, Thomas Castells, Josiane Gallot, Yann Simon Durand, Christine Euthine, Vanessa Gu, Yansong Béchet, Daniel Peinnequin, André Lefai, Etienne Freyssenet, Damien PLoS One Research Article Sirtuin 1 (SIRT1), a NAD(+)-dependent protein deacetylase, has emerged as a main determinant of whole body homeostasis in mammals by regulating a large spectrum of transcriptional regulators in metabolically relevant tissue such as liver, adipose tissue and skeletal muscle. Sterol regulatory element binding protein (SREBP)-1c is a transcription factor that controls the expression of genes related to fatty acid and triglyceride synthesis in tissues with high lipid synthesis rates such as adipose tissue and liver. Previous studies indicate that SIRT1 can regulate the expression and function of SREBP-1c in liver. In the present study, we determined whether SIRT1 regulates SREBP-1c expression in skeletal muscle. SREBP-1c mRNA and protein levels were decreased in the gastrocnemius muscle of mice harboring deletion of the catalytic domain of SIRT1 (SIRT1(Δex4/Δex4) mice). By contrast, adenoviral expression of SIRT1 in human myotubes increased SREBP-1c mRNA and protein levels. Importantly, SREBP-1c promoter transactivation, which was significantly increased in response to SIRT1 overexpression by gene electrotransfer in skeletal muscle, was completely abolished when liver X receptor (LXR) response elements were deleted. Finally, our in vivo data from SIRT1(Δex4/Δex4) mice and in vitro data from human myotubes overexpressing SIRT1 show that SIRT1 regulates LXR acetylation in skeletal muscle cells. This suggests a possible mechanism by which the regulation of SREBP-1c gene expression by SIRT1 may require the deacetylation of LXR transcription factors. Public Library of Science 2012-09-11 /pmc/articles/PMC3439460/ /pubmed/22984430 http://dx.doi.org/10.1371/journal.pone.0043490 Text en © 2012 Defour et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Defour, Aurélia
Dessalle, Kevin
Castro Perez, Andréa
Poyot, Thomas
Castells, Josiane
Gallot, Yann Simon
Durand, Christine
Euthine, Vanessa
Gu, Yansong
Béchet, Daniel
Peinnequin, André
Lefai, Etienne
Freyssenet, Damien
Sirtuin 1 Regulates SREBP-1c Expression in a LXR-Dependent Manner in Skeletal Muscle
title Sirtuin 1 Regulates SREBP-1c Expression in a LXR-Dependent Manner in Skeletal Muscle
title_full Sirtuin 1 Regulates SREBP-1c Expression in a LXR-Dependent Manner in Skeletal Muscle
title_fullStr Sirtuin 1 Regulates SREBP-1c Expression in a LXR-Dependent Manner in Skeletal Muscle
title_full_unstemmed Sirtuin 1 Regulates SREBP-1c Expression in a LXR-Dependent Manner in Skeletal Muscle
title_short Sirtuin 1 Regulates SREBP-1c Expression in a LXR-Dependent Manner in Skeletal Muscle
title_sort sirtuin 1 regulates srebp-1c expression in a lxr-dependent manner in skeletal muscle
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3439460/
https://www.ncbi.nlm.nih.gov/pubmed/22984430
http://dx.doi.org/10.1371/journal.pone.0043490
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