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

Julien Bricambert, Dimitri Favre, Saška Brajkovic, Amélie Bonnefond, Raphael Boutry, Roberto Salvi, Valérie Plaisance, Mohamed Chikri, Giulia Chinetti-Gbaguidi, Bart Staels, Vittorio Giusti, Robert Caiazzo, François Pattou, Gérard Waeber, Philippe Froguel, Amar Abderrahmani

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)1200-1207
Number of pages8
JournalMolecular Metabolism
Volume5
Issue number12
DOIs
Publication statusPublished - 1 Dec 2016

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Histone Deacetylases
Adipocytes
Obesity
White Adipose Tissue
Adipokines
Intra-Abdominal Fat
High Fat Diet
RNA Interference
Gene Expression
Obese Mice
Hypoxia
Real-Time Polymerase Chain Reaction
Proteins
Western Blotting
RNA
Insulin
Weights and Measures
Glucose

Keywords

  • Adipocytes
  • Adipokines
  • Histone deacetylases
  • Insulin resistance
  • Obesity

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Bricambert, J., Favre, D., Brajkovic, S., Bonnefond, A., Boutry, R., Salvi, R., ... Abderrahmani, A. (2016). Impaired histone deacetylases 5 and 6 expression mimics the effects of obesity and hypoxia on adipocyte function. Molecular Metabolism, 5(12), 1200-1207. https://doi.org/10.1016/j.molmet.2016.09.011

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.

In: Molecular Metabolism, Vol. 5, No. 12, 01.12.2016, p. 1200-1207.

Research output: Contribution to journalArticle

Bricambert, J, Favre, D, Brajkovic, S, Bonnefond, A, Boutry, R, Salvi, R, Plaisance, V, Chikri, M, Chinetti-Gbaguidi, G, Staels, B, Giusti, V, Caiazzo, R, Pattou, F, Waeber, G, Froguel, P & Abderrahmani, A 2016, 'Impaired histone deacetylases 5 and 6 expression mimics the effects of obesity and hypoxia on adipocyte function', Molecular Metabolism, vol. 5, no. 12, pp. 1200-1207. https://doi.org/10.1016/j.molmet.2016.09.011
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. In: Molecular Metabolism. 2016 ; Vol. 5, No. 12. pp. 1200-1207.
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AU - Bricambert, Julien

AU - Favre, Dimitri

AU - Brajkovic, Saška

AU - Bonnefond, Amélie

AU - Boutry, Raphael

AU - Salvi, Roberto

AU - Plaisance, Valérie

AU - Chikri, Mohamed

AU - Chinetti-Gbaguidi, Giulia

AU - Staels, Bart

AU - Giusti, Vittorio

AU - Caiazzo, Robert

AU - Pattou, François

AU - Waeber, Gérard

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