The histone deacetylase inhibiting drug Entinostat induces lipid accumulation in differentiated HepaRG cells
Journal article, 2016

Dietary overload of toxic, free metabolic intermediates leads to disrupted insulin signalling and fatty liver disease. However, it was recently reported that this pathway might not be universal: depletion of histone deacetylase (HDAC) enhances insulin sensitivity alongside hepatic lipid accumulation in mice, but the mechanistic role of microscopic lipid structure in this effect remains unclear. Here we study the effect of Entinostat, a synthetic HDAC inhibitor undergoing clinical trials, on hepatic lipid metabolism in the paradigmatic HepaRG liver cell line. Specifically, we statistically quantify lipid droplet morphology at single cell level utilizing label-free microscopy, coherent anti-Stokes Raman scattering, supported by gene expression. We observe Entinostat efficiently rerouting carbohydrates and free-fatty acids into lipid droplets, upregulating lipid coat protein gene Plin4, and relocating droplets nearer to the nucleus. Our results demonstrate the power of Entinostat to promote lipid synthesis and storage, allowing reduced systemic sugar levels and sequestration of toxic metabolites within protected protein-coated droplets, suggesting a potential therapeutic strategy for diseases such as diabetes and metabolic syndrome.

lysine acetylation



Science & Technology - Other Topics



perilipin family






A. D. G. Nunn

Sapienza University of Rome

Istituto Italiano di Tecnologia

T. Scopigno

Sapienza University of Rome

Istituto Italiano di Tecnologia

N. Pediconi

Sapienza University of Rome

M. Levrero

Sapienza University of Rome

Hopital de la Croix-Rousse

Clinical and Research Memory Center of Lyon

Istituto Italiano di Tecnologia

Henning Hagman

Molecular Microscopy and Biotechnology

Juris Kiskis

Chalmers, Biology and Biological Engineering, Food and Nutrition Science

Annika Enejder

Chalmers, Biology and Biological Engineering, Food and Nutrition Science

Scientific Reports

2045-2322 (ISSN) 20452322 (eISSN)

Vol. 6 28025

Subject Categories

Biochemistry and Molecular Biology





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