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Animal Models

Attenuation of diet-induced obesity and induction of white fat browning with a chemical inhibitor of histone deacetylases

International Journal of Obesity volume 41, pages 289–298 (2017)Cite this article

Subjects

Abstract

Background/objectives:

In the last decade, a strict link between epigenetics and metabolism has been demonstrated. Histone deacetylases (HDACs) have emerged as key epigenetic regulators involved in metabolic homeostasis in normal and pathologic conditions. Here we investigated the effect of the class I HDAC inhibitor MS-275 in a model of obesity induced by a high-fat diet (HFD).

Methods:

C57BL6/J male mice were fed HFD for 17 weeks and then randomized in two groups, treated intraperitoneally with vehicle dimethylsulfoxide (DMSO) or with the class I selective HDAC inhibitor MS-275 every other day for 22 days. Glucose tolerance test and measurement of body temperature during cold exposure were performed. Adipose tissues and liver were phenotypically characterized through histological analysis. Gene and protein expression analysis of brown and white adipose tissues (WATs) were performed.

Results:

MS-275 treated mice showed 10% reduction of body weight, lower adipocyte size and improved glucose tolerance. Inhibition of class I HDAC determined reduction of adipocyte size and of fat mass, paralleled by higher expression of adipose functionality markers and by increased rate of lipolysis and fatty acid β-oxidation. MS-275 also promoted thermogenic capacity, related to ‘browning’ of visceral and subcutaneous WAT, showing increased expression of uncoupling protein 1. In brown adipose tissue, we observed limited effects on gene expression and only reduction of brown adipocyte size.

Conclusions:

This study provides evidence that class I HDAC inhibition stimulated functionality and oxidative potential of adipose tissue, improving glucose tolerance and ameliorating the metabolic profile in diet-induced obese mice.

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Acknowledgements

We thank Dr Gabriele Campana (Università degli Studi di Bologna) for providing us human adipose stromal cell and the other members of the laboratory for valuable discussion. We are grateful with Elda Desiderio Pinto for administrative support. This research was supported by grants from FP6 LSHM-CT2006-037498 and PRIN 2009K7R7NA to MC.

Author information

Author notes

  1. S Barilla

    Present address: 3Current address: Karolinska Institutet, Institutionen för biovetenskaper och näringslära, Novum, Hiss D, Plan 7 Hälsovägen 7, S-14157 Huddinge.,

  2. M Giudici

    Present address: 4Current address: Wallenberg Centre for Protein Research, School of Biotechnology, Division of Protein Technology KTH, AlbaNova plan 3, SE-106 91, Stockholm.,

Authors and Affiliations

  1. Dipartimento di Scienze Farmacologiche e Biomolecolari, DiSFeB, Università degli Studi di Milano, Milano, Italy

    A Ferrari, E Fiorino, R Longo, S Barilla, N Mitro, G Cermenati, M Giudici, D Caruso, U Guerrini, E De Fabiani & M Crestani

  2. Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza Università di Roma, Roma, Italy

    A Mai

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Correspondence to M Crestani.

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Ferrari, A., Fiorino, E., Longo, R. et al. Attenuation of diet-induced obesity and induction of white fat browning with a chemical inhibitor of histone deacetylases. Int J Obes 41, 289–298 (2017). https://doi.org/10.1038/ijo.2016.191

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