title: Resveratrol Regulates the Quiescence-Like Induction of Activated Stellate Cells by Modulating the PPARγ/SIRT1 Ratio.
abstract: 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.
authors.affiliation: Departamento de Morfologia, IB, Universidade Federal de Pelotas (UFPel), av. Duque de Caxias, 250, CEP 96 030 000, Pelotas, RS, Brazil.|Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), rua Ramiro Barcelos, 2600-Anexo I, CEP 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Izabel Cristina Custódio
authors.initials: IC
authors.lastname: de Souza
authors.affiliation: Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), rua Ramiro Barcelos, 2600-Anexo I, CEP 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Leo Anderson Meira
authors.initials: LA
authors.lastname: Martins
authors.affiliation: Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), rua Ramiro Barcelos, 2600-Anexo I, CEP 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: de Vasconcelos
authors.affiliation: Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), rua Ramiro Barcelos, 2600-Anexo I, CEP 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Cleverson Moraes
authors.initials: CM
authors.lastname: de Oliveira
authors.affiliation: Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), rua Ramiro Barcelos, 2600-Anexo I, CEP 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Florencia
authors.initials: F
authors.lastname: Barbé-Tuana
authors.affiliation: Departamento de Química, ICET, Universidade Federal do Mato Grosso (UFMT), Cuiabá, MT, Brazil.
authors.forename: Cláudia Balbinotti
authors.initials: CB
authors.lastname: Andrade
authors.affiliation: Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), rua Ramiro Barcelos, 2600-Anexo I, CEP 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Letícia Ferreira
authors.initials: LF
authors.lastname: Pettenuzzo
authors.affiliation: Departamento de Histologia e Embriologia, ICB, PABCAM, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.
authors.forename: Radovan
authors.initials: R
authors.lastname: Borojevic
authors.affiliation: Departamento de Biofísica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Rogério
authors.initials: R
authors.lastname: Margis
authors.affiliation: Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), rua Ramiro Barcelos, 2600-Anexo I, CEP 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Regina
authors.initials: R
authors.lastname: Guaragna
authors.affiliation: Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), rua Ramiro Barcelos, 2600-Anexo I, CEP 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Fátima Costa Rodrigues
authors.initials: FC
authors.lastname: Guma
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D005355:Fibrosis / Q000235:genetics* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000378:metabolism; D006801:Humans; D007728:Kupffer Cells / Q000378:metabolism; D066292:Lipid Droplets / Q000378:metabolism*; D050155:Lipogenesis / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D051379:Mice; D032446:Myoblasts / Q000378:metabolism; D047495:PPAR gamma / Q000096:biosynthesis* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000096:biosynthesis* / Q000378:metabolism; D013267:Stilbenes / Q000008:administration & dosage; D014801:Vitamin A / Q000378:metabolism
chemical_list: D047495:PPAR gamma; D012333:RNA, Messenger; D013267:Stilbenes; D014801:Vitamin A; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D000077185:Resveratrol
keywords: GRX; HEPATIC STELLATE CELLS; LIPID ACCUMULATION; PPARγ; RESVERATROL; SIRT1