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Resveratrol Regulates the Quiescence‐Like Induction of Activated Stellate Cells by Modulating the PPARγ/SIRT1 Ratio
Author(s) -
de Souza Izabel Cristina Custódio,
Martins Leo Anderson Meira,
de Vasconcelos Mariana,
de Oliveira Cleverson Moraes,
BarbéTuana Florencia,
Andrade Cláudia Balbinotti,
Pettenuzzo Letícia Ferreira,
Borojevic Radovan,
Margis Rogério,
Guaragna Regina,
Guma Fátima Costa Rodrigues
Publication year - 2015
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25181
Subject(s) - resveratrol , hepatic stellate cell , lipid droplet , lipogenesis , peroxisome proliferator activated receptor , microbiology and biotechnology , chemistry , sirtuin 1 , adipogenesis , biochemistry , biology , lipid metabolism , receptor , downregulation and upregulation , endocrinology , in vitro , gene
The activation of hepatic stellate cell (HSC), from a quiescent cell featuring cytoplasmic lipid droplets to a proliferative myofibroblast, plays an important role in liver fibrosis development. The GRX line is an activated HSC model that can be induced by all‐trans‐ retinol to accumulate lipid droplets. Resveratrol is known for activating Sirtuin1 (SIRT1), a NAD + ‐dependent deacetylase that suppresses the activity of peroxisome proliferator‐activated receptor gamma (PPARγ), an important adipogenic transcription factor involved in the quiescence maintenance of HSC. We evaluated the effects of 0.1 μM of resveratrol in retinol‐induced GRX quiescence by investigating the interference of SIRT1 and PPARγ on cell lipogenesis. GRX lipid accumulation was evaluated through Oil‐red O staining, triacylglycerides quantification, and [ 14 C] acetate incorporation into lipids. mRNA expression and protein content of SIRT1 and PPARγ were measured by RT‐PCR and immunoblotting, respectively. Resveratrol‐mediated SIRT1 stimuli did not induce lipogenesis and reduced the retinol‐mediated fat‐storing capacity in GRX. In order to support our results, we established a cell culture model of transgenic super expression of PPARγ in GRX cells (GRXPγ). Resveratrol reduced lipid droplets accumulation in GRXPγ cells. These results suggest that the PPARγ/SIRT1 ratio plays an important role in the fate of HSC. Thus, whenever the PPARγ activity is greater than SIRT1 activity the lipogenesis is enabled. J. Cell. Biochem. 116: 2304–2312, 2015. © 2015 Wiley Periodicals, Inc.