Scopolin ameliorates high-fat diet induced hepatic steatosis in mice: potential involvement of SIRT1-mediated signaling cascades in the liver

Abstract The present study aimed to investigate whether scopolin exhibits beneficial effects on high-fat diet (HFD)-induced hepatic steatosis in mice. The involvement of sirtuin 1 (SIRT1) as a molecular target for scopolin was also explored. Scopolin decreased the Km of SIRT1 for p53 and nicotinamid...

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Autores principales:	Ahyoung Yoo, Vikram P. Narayan, Eun Young Hong, Wan Kyunn Whang, Taesun Park
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e6e738754bee447ca9d92cea5f53f3da
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spelling	oai:doaj.org-article:e6e738754bee447ca9d92cea5f53f3da2021-12-02T15:05:15ZScopolin ameliorates high-fat diet induced hepatic steatosis in mice: potential involvement of SIRT1-mediated signaling cascades in the liver10.1038/s41598-017-02416-62045-2322https://doaj.org/article/e6e738754bee447ca9d92cea5f53f3da2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02416-6https://doaj.org/toc/2045-2322Abstract The present study aimed to investigate whether scopolin exhibits beneficial effects on high-fat diet (HFD)-induced hepatic steatosis in mice. The involvement of sirtuin 1 (SIRT1) as a molecular target for scopolin was also explored. Scopolin decreased the Km of SIRT1 for p53 and nicotinamide adenine dinucleotide without altering Vmax in a cell-free system. Scopolin alleviated oleic acid-induced lipid accumulation and downregulation of SIRT1 activity in HepG2 cells, and these beneficial effects of scopolin were abolished in the presence of SIRT1 inhibitor. Mice administered 0.02% scopolin for 8 weeks exhibited improved phenotypes of HFD-induced hepatic steatosis along with increased hepatic SIRT1 activity and protein expression. Scopolin resulted in increased deacetylation of sterol regulatory element-binding protein 1c with subsequent downregulation of lipogenic genes, and enhanced deacetylation of protein peroxisome proliferator-activated receptor-γ coactivator 1α with upregulation of fatty acid oxidation genes in livers. Scopolin also enhanced deacetylation of nuclear factor-kappa enhancer binding protein and liver kinase B1 (LKB1), facilitating LKB1/AMP-activated protein kinase signaling cascades. Scopolin attenuated hepatic steatosis through activation of SIRT1-mediated signaling cascades, a potent regulator of lipid homeostasis. Increased hepatic SIRT1 activity and protein expression appeared to be associated with these beneficial effects of scopolin.Ahyoung YooVikram P. NarayanEun Young HongWan Kyunn WhangTaesun ParkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ahyoung Yoo Vikram P. Narayan Eun Young Hong Wan Kyunn Whang Taesun Park Scopolin ameliorates high-fat diet induced hepatic steatosis in mice: potential involvement of SIRT1-mediated signaling cascades in the liver
description	Abstract The present study aimed to investigate whether scopolin exhibits beneficial effects on high-fat diet (HFD)-induced hepatic steatosis in mice. The involvement of sirtuin 1 (SIRT1) as a molecular target for scopolin was also explored. Scopolin decreased the Km of SIRT1 for p53 and nicotinamide adenine dinucleotide without altering Vmax in a cell-free system. Scopolin alleviated oleic acid-induced lipid accumulation and downregulation of SIRT1 activity in HepG2 cells, and these beneficial effects of scopolin were abolished in the presence of SIRT1 inhibitor. Mice administered 0.02% scopolin for 8 weeks exhibited improved phenotypes of HFD-induced hepatic steatosis along with increased hepatic SIRT1 activity and protein expression. Scopolin resulted in increased deacetylation of sterol regulatory element-binding protein 1c with subsequent downregulation of lipogenic genes, and enhanced deacetylation of protein peroxisome proliferator-activated receptor-γ coactivator 1α with upregulation of fatty acid oxidation genes in livers. Scopolin also enhanced deacetylation of nuclear factor-kappa enhancer binding protein and liver kinase B1 (LKB1), facilitating LKB1/AMP-activated protein kinase signaling cascades. Scopolin attenuated hepatic steatosis through activation of SIRT1-mediated signaling cascades, a potent regulator of lipid homeostasis. Increased hepatic SIRT1 activity and protein expression appeared to be associated with these beneficial effects of scopolin.
format	article
author	Ahyoung Yoo Vikram P. Narayan Eun Young Hong Wan Kyunn Whang Taesun Park
author_facet	Ahyoung Yoo Vikram P. Narayan Eun Young Hong Wan Kyunn Whang Taesun Park
author_sort	Ahyoung Yoo
title	Scopolin ameliorates high-fat diet induced hepatic steatosis in mice: potential involvement of SIRT1-mediated signaling cascades in the liver
title_short	Scopolin ameliorates high-fat diet induced hepatic steatosis in mice: potential involvement of SIRT1-mediated signaling cascades in the liver
title_full	Scopolin ameliorates high-fat diet induced hepatic steatosis in mice: potential involvement of SIRT1-mediated signaling cascades in the liver
title_fullStr	Scopolin ameliorates high-fat diet induced hepatic steatosis in mice: potential involvement of SIRT1-mediated signaling cascades in the liver
title_full_unstemmed	Scopolin ameliorates high-fat diet induced hepatic steatosis in mice: potential involvement of SIRT1-mediated signaling cascades in the liver
title_sort	scopolin ameliorates high-fat diet induced hepatic steatosis in mice: potential involvement of sirt1-mediated signaling cascades in the liver
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e6e738754bee447ca9d92cea5f53f3da
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Scopolin ameliorates high-fat diet induced hepatic steatosis in mice: potential involvement of SIRT1-mediated signaling cascades in the liver

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