Gpbar1 agonism promotes a Pgc-1α-dependent browning of white adipose tissue and energy expenditure and reverses diet-induced steatohepatitis in mice

Gpbar1 is a bile acid activated receptor for secondary bile acids. Here we have investigated the mechanistic role of Gpbar1 in the regulation of adipose tissues functionality in a murine model of steatohepatitis (NASH). Feeding wild type and Gpbar1(−/−) mice with a high fat diet-fructose (HFD-F) lea...

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Autores principales: Carino, Adriana, Cipriani, Sabrina, Marchianò, Silvia, Biagioli, Michele, Scarpelli, Paolo, Zampella, Angela, Monti, Maria Chiara, Fiorucci, Stefano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651899/
https://www.ncbi.nlm.nih.gov/pubmed/29057935
http://dx.doi.org/10.1038/s41598-017-13102-y
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author Carino, Adriana
Cipriani, Sabrina
Marchianò, Silvia
Biagioli, Michele
Scarpelli, Paolo
Zampella, Angela
Monti, Maria Chiara
Fiorucci, Stefano
author_facet Carino, Adriana
Cipriani, Sabrina
Marchianò, Silvia
Biagioli, Michele
Scarpelli, Paolo
Zampella, Angela
Monti, Maria Chiara
Fiorucci, Stefano
author_sort Carino, Adriana
collection PubMed
description Gpbar1 is a bile acid activated receptor for secondary bile acids. Here we have investigated the mechanistic role of Gpbar1 in the regulation of adipose tissues functionality in a murine model of steatohepatitis (NASH). Feeding wild type and Gpbar1(−/−) mice with a high fat diet-fructose (HFD-F) lead to development of NASH-like features. Treating HFD-F mice with 6β-ethyl-3a,7b-dihydroxy-5b-cholan-24-ol (BAR501), a selective Gpbar1-ligand, reversed insulin resistance and histologic features of NASH, increased the weight of epWAT and BAT functionality and promoted energy expenditure and the browning of epWAT as assessed by measuring expression of Ucp1 and Pgc-1α. The beneficial effects of BAR501 were lost in Gpbar1(−/−) mice. In vitro, BAR501 promoted the browning of 3T3-L1 cells a pre-adipocyte cell line and recruitment of CREB to the promoter of Pgc-1α. In conclusion, Gpbar1 agonism ameliorates liver histology in a rodent model of NASH and promotes the browning of white adipose tissue.
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spelling pubmed-56518992017-10-26 Gpbar1 agonism promotes a Pgc-1α-dependent browning of white adipose tissue and energy expenditure and reverses diet-induced steatohepatitis in mice Carino, Adriana Cipriani, Sabrina Marchianò, Silvia Biagioli, Michele Scarpelli, Paolo Zampella, Angela Monti, Maria Chiara Fiorucci, Stefano Sci Rep Article Gpbar1 is a bile acid activated receptor for secondary bile acids. Here we have investigated the mechanistic role of Gpbar1 in the regulation of adipose tissues functionality in a murine model of steatohepatitis (NASH). Feeding wild type and Gpbar1(−/−) mice with a high fat diet-fructose (HFD-F) lead to development of NASH-like features. Treating HFD-F mice with 6β-ethyl-3a,7b-dihydroxy-5b-cholan-24-ol (BAR501), a selective Gpbar1-ligand, reversed insulin resistance and histologic features of NASH, increased the weight of epWAT and BAT functionality and promoted energy expenditure and the browning of epWAT as assessed by measuring expression of Ucp1 and Pgc-1α. The beneficial effects of BAR501 were lost in Gpbar1(−/−) mice. In vitro, BAR501 promoted the browning of 3T3-L1 cells a pre-adipocyte cell line and recruitment of CREB to the promoter of Pgc-1α. In conclusion, Gpbar1 agonism ameliorates liver histology in a rodent model of NASH and promotes the browning of white adipose tissue. Nature Publishing Group UK 2017-10-20 /pmc/articles/PMC5651899/ /pubmed/29057935 http://dx.doi.org/10.1038/s41598-017-13102-y Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Carino, Adriana
Cipriani, Sabrina
Marchianò, Silvia
Biagioli, Michele
Scarpelli, Paolo
Zampella, Angela
Monti, Maria Chiara
Fiorucci, Stefano
Gpbar1 agonism promotes a Pgc-1α-dependent browning of white adipose tissue and energy expenditure and reverses diet-induced steatohepatitis in mice
title Gpbar1 agonism promotes a Pgc-1α-dependent browning of white adipose tissue and energy expenditure and reverses diet-induced steatohepatitis in mice
title_full Gpbar1 agonism promotes a Pgc-1α-dependent browning of white adipose tissue and energy expenditure and reverses diet-induced steatohepatitis in mice
title_fullStr Gpbar1 agonism promotes a Pgc-1α-dependent browning of white adipose tissue and energy expenditure and reverses diet-induced steatohepatitis in mice
title_full_unstemmed Gpbar1 agonism promotes a Pgc-1α-dependent browning of white adipose tissue and energy expenditure and reverses diet-induced steatohepatitis in mice
title_short Gpbar1 agonism promotes a Pgc-1α-dependent browning of white adipose tissue and energy expenditure and reverses diet-induced steatohepatitis in mice
title_sort gpbar1 agonism promotes a pgc-1α-dependent browning of white adipose tissue and energy expenditure and reverses diet-induced steatohepatitis in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651899/
https://www.ncbi.nlm.nih.gov/pubmed/29057935
http://dx.doi.org/10.1038/s41598-017-13102-y
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