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Using genetic and pharmacologic approaches, we show that G protein\u2013coupled bile acid\u2013activated receptor 1 (GPBAR1) agonism reverses liver and vascular damage in mouse models of NASH. NASH is associated with accelerated vascular inflammation representing an independent risk factor for development of cardiovascular diseases and cardiovascular\u2010related mortality. GPBAR1, also known as TGR5, is a G protein\u2013coupled receptor for secondary bile acids that reduces inflammation and promotes energy expenditure. Using genetic and pharmacologic approaches, we investigated whether GPBAR1 agonism by 6\u03b2\u2010ethyl\u20103\u03b1,7\u03b2\u2010dihydroxy\u20105\u03b2\u2010cholan\u201024\u2010ol (BAR501) reverses liver and vascular damage induced by exposure to a diet enriched in fat and fructose (HFD\u2010F). Treating HFD\u2010F mice with BAR501 reversed liver injury and promoted the browning of white adipose tissue in a Gpbar1\u2010dependent manner. Feeding HFD\u2010F resulted in vascular damage, as shown by the increased aorta intima\u2010media thickness and increased expression of inflammatory genes (IL\u20106, TNF\u2010\u03b1, iNOS, and F4\/80) and adhesion molecules (VCAM, intercellular adhesion molecule\u20101, and endothelial selectin) in the aorta, while reducing the expression of genes involved in NO and hydrogen sulfide generation, severely altering vasomotor activities of aortic rings in an\n                    <jats:italic>ex vivo<\/jats:italic>\n                    assay. BAR501 reversed this pattern in a Gpbar1\u2010dependent manner, highlighting a potential role for GPBAR1 agonism in treating the liver and vascular component of NASH.\u2014Carino, A., Marchian\u00f2, S., Biagioli, M., Bucci, M., Vellecco, V., Brancaleone, V., Fiorucci, C., Zampella, A., Monti, M. C., Distrutti, E., Fiorucci, S. Agonism for the bile acid receptor GPBAR1 reverses liver and vascular damage in a mouse model of steatohepatitis. FASEB J. 33, 2809\u20132822 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801373rr","type":"journal-article","created":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T14:13:12Z","timestamp":1539180792000},"page":"2809-2822","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Agonism for the bile acid receptor GPBAR1 reverses liver and vascular damage in a mouse model of steatohepatitis"],"prefix":"10.1096","volume":"33","author":[{"given":"Adriana","family":"Carino","sequence":"first","affiliation":[{"name":"Department of Surgical and Biomedical Sciences University of Perugia Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Marchian\u00f2","sequence":"additional","affiliation":[{"name":"Department 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