Cargando…

Impaired histone deacetylases 5 and 6 expression mimics the effects of obesity and hypoxia on adipocyte function

OBJECTIVE: The goal of the study was to investigate the role of histone deacetylases (HDACs) in adipocyte function associated with obesity and hypoxia. METHODS: Total proteins and RNA were prepared from human visceral adipose tissues (VAT) of human obese and normal weight subjects and from white adi...

Descripción completa

Detalles Bibliográficos
Autores principales: Bricambert, Julien, Favre, Dimitri, Brajkovic, Saška, Bonnefond, Amélie, Boutry, Raphael, Salvi, Roberto, Plaisance, Valérie, Chikri, Mohamed, Chinetti-Gbaguidi, Giulia, Staels, Bart, Giusti, Vittorio, Caiazzo, Robert, Pattou, François, Waeber, Gérard, Froguel, Philippe, Abderrahmani, Amar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123204/
https://www.ncbi.nlm.nih.gov/pubmed/27900262
http://dx.doi.org/10.1016/j.molmet.2016.09.011
_version_ 1782469684785840128
author Bricambert, Julien
Favre, Dimitri
Brajkovic, Saška
Bonnefond, Amélie
Boutry, Raphael
Salvi, Roberto
Plaisance, Valérie
Chikri, Mohamed
Chinetti-Gbaguidi, Giulia
Staels, Bart
Giusti, Vittorio
Caiazzo, Robert
Pattou, François
Waeber, Gérard
Froguel, Philippe
Abderrahmani, Amar
author_facet Bricambert, Julien
Favre, Dimitri
Brajkovic, Saška
Bonnefond, Amélie
Boutry, Raphael
Salvi, Roberto
Plaisance, Valérie
Chikri, Mohamed
Chinetti-Gbaguidi, Giulia
Staels, Bart
Giusti, Vittorio
Caiazzo, Robert
Pattou, François
Waeber, Gérard
Froguel, Philippe
Abderrahmani, Amar
author_sort Bricambert, Julien
collection PubMed
description OBJECTIVE: The goal of the study was to investigate the role of histone deacetylases (HDACs) in adipocyte function associated with obesity and hypoxia. METHODS: Total proteins and RNA were prepared from human visceral adipose tissues (VAT) of human obese and normal weight subjects and from white adipose tissue (WAT) of C57Bl6-Rj mice fed a normal or high fat diet (HFD) for 16 weeks. HDAC activity was measured by colorimetric assay whereas the gene and protein expression were monitored by real-time PCR and by western blotting, respectively. RNA interference (RNAi) was used to silence the expression of genes in 3T3-L1 adipocytes. RESULTS: Total HDAC activity was decreased in VAT and WAT from obese individuals and from mice fed a HFD, respectively. The HDAC activity reduction was associated with decreased HDAC5/Hdac5 and HDAC6/Hdac6 expression in human and mice adipocyte fraction. Similarly, hypoxia hampered total Hdac activity and reduced the expression of Hdac5 and Hdac6 in 3T3-L1 adipocytes. The decrease of both Hdac5 and Hdac6 by hypoxia was associated with altered expression of adipokines and of the inducible cAMP early repressor (Icer), a key repressor that is defective in human and mice obesity. Silencing of Icer in adipocytes reproduced the changes in adipokine levels under hypoxia and obesity, suggesting a causative effect. Finally, modeling the defect of the two Hdacs in adipocytes by RNAi or selective inhibitors mimicked the effects of hypoxia on the expression of Icer, leading to impairment of insulin-induced glucose uptake. CONCLUSION: Hdac5 and Hdac6 expression are required for the adequate expression of Icer and adipocyte function. Altered adipose expression of the two Hdacs in obesity by hypoxia may contribute to the development of metabolic abnormalities.
format Online
Article
Text
id pubmed-5123204
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-51232042016-11-29 Impaired histone deacetylases 5 and 6 expression mimics the effects of obesity and hypoxia on adipocyte function Bricambert, Julien Favre, Dimitri Brajkovic, Saška Bonnefond, Amélie Boutry, Raphael Salvi, Roberto Plaisance, Valérie Chikri, Mohamed Chinetti-Gbaguidi, Giulia Staels, Bart Giusti, Vittorio Caiazzo, Robert Pattou, François Waeber, Gérard Froguel, Philippe Abderrahmani, Amar Mol Metab Brief Communication OBJECTIVE: The goal of the study was to investigate the role of histone deacetylases (HDACs) in adipocyte function associated with obesity and hypoxia. METHODS: Total proteins and RNA were prepared from human visceral adipose tissues (VAT) of human obese and normal weight subjects and from white adipose tissue (WAT) of C57Bl6-Rj mice fed a normal or high fat diet (HFD) for 16 weeks. HDAC activity was measured by colorimetric assay whereas the gene and protein expression were monitored by real-time PCR and by western blotting, respectively. RNA interference (RNAi) was used to silence the expression of genes in 3T3-L1 adipocytes. RESULTS: Total HDAC activity was decreased in VAT and WAT from obese individuals and from mice fed a HFD, respectively. The HDAC activity reduction was associated with decreased HDAC5/Hdac5 and HDAC6/Hdac6 expression in human and mice adipocyte fraction. Similarly, hypoxia hampered total Hdac activity and reduced the expression of Hdac5 and Hdac6 in 3T3-L1 adipocytes. The decrease of both Hdac5 and Hdac6 by hypoxia was associated with altered expression of adipokines and of the inducible cAMP early repressor (Icer), a key repressor that is defective in human and mice obesity. Silencing of Icer in adipocytes reproduced the changes in adipokine levels under hypoxia and obesity, suggesting a causative effect. Finally, modeling the defect of the two Hdacs in adipocytes by RNAi or selective inhibitors mimicked the effects of hypoxia on the expression of Icer, leading to impairment of insulin-induced glucose uptake. CONCLUSION: Hdac5 and Hdac6 expression are required for the adequate expression of Icer and adipocyte function. Altered adipose expression of the two Hdacs in obesity by hypoxia may contribute to the development of metabolic abnormalities. Elsevier 2016-10-05 /pmc/articles/PMC5123204/ /pubmed/27900262 http://dx.doi.org/10.1016/j.molmet.2016.09.011 Text en © 2016 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Brief Communication
Bricambert, Julien
Favre, Dimitri
Brajkovic, Saška
Bonnefond, Amélie
Boutry, Raphael
Salvi, Roberto
Plaisance, Valérie
Chikri, Mohamed
Chinetti-Gbaguidi, Giulia
Staels, Bart
Giusti, Vittorio
Caiazzo, Robert
Pattou, François
Waeber, Gérard
Froguel, Philippe
Abderrahmani, Amar
Impaired histone deacetylases 5 and 6 expression mimics the effects of obesity and hypoxia on adipocyte function
title Impaired histone deacetylases 5 and 6 expression mimics the effects of obesity and hypoxia on adipocyte function
title_full Impaired histone deacetylases 5 and 6 expression mimics the effects of obesity and hypoxia on adipocyte function
title_fullStr Impaired histone deacetylases 5 and 6 expression mimics the effects of obesity and hypoxia on adipocyte function
title_full_unstemmed Impaired histone deacetylases 5 and 6 expression mimics the effects of obesity and hypoxia on adipocyte function
title_short Impaired histone deacetylases 5 and 6 expression mimics the effects of obesity and hypoxia on adipocyte function
title_sort impaired histone deacetylases 5 and 6 expression mimics the effects of obesity and hypoxia on adipocyte function
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123204/
https://www.ncbi.nlm.nih.gov/pubmed/27900262
http://dx.doi.org/10.1016/j.molmet.2016.09.011
work_keys_str_mv AT bricambertjulien impairedhistonedeacetylases5and6expressionmimicstheeffectsofobesityandhypoxiaonadipocytefunction
AT favredimitri impairedhistonedeacetylases5and6expressionmimicstheeffectsofobesityandhypoxiaonadipocytefunction
AT brajkovicsaska impairedhistonedeacetylases5and6expressionmimicstheeffectsofobesityandhypoxiaonadipocytefunction
AT bonnefondamelie impairedhistonedeacetylases5and6expressionmimicstheeffectsofobesityandhypoxiaonadipocytefunction
AT boutryraphael impairedhistonedeacetylases5and6expressionmimicstheeffectsofobesityandhypoxiaonadipocytefunction
AT salviroberto impairedhistonedeacetylases5and6expressionmimicstheeffectsofobesityandhypoxiaonadipocytefunction
AT plaisancevalerie impairedhistonedeacetylases5and6expressionmimicstheeffectsofobesityandhypoxiaonadipocytefunction
AT chikrimohamed impairedhistonedeacetylases5and6expressionmimicstheeffectsofobesityandhypoxiaonadipocytefunction
AT chinettigbaguidigiulia impairedhistonedeacetylases5and6expressionmimicstheeffectsofobesityandhypoxiaonadipocytefunction
AT staelsbart impairedhistonedeacetylases5and6expressionmimicstheeffectsofobesityandhypoxiaonadipocytefunction
AT giustivittorio impairedhistonedeacetylases5and6expressionmimicstheeffectsofobesityandhypoxiaonadipocytefunction
AT caiazzorobert impairedhistonedeacetylases5and6expressionmimicstheeffectsofobesityandhypoxiaonadipocytefunction
AT pattoufrancois impairedhistonedeacetylases5and6expressionmimicstheeffectsofobesityandhypoxiaonadipocytefunction
AT waebergerard impairedhistonedeacetylases5and6expressionmimicstheeffectsofobesityandhypoxiaonadipocytefunction
AT froguelphilippe impairedhistonedeacetylases5and6expressionmimicstheeffectsofobesityandhypoxiaonadipocytefunction
AT abderrahmaniamar impairedhistonedeacetylases5and6expressionmimicstheeffectsofobesityandhypoxiaonadipocytefunction