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Rodent studies have shown that MRAs can prevent adverse metabolic consequences of obesity but an elucidation of underlying molecular mechanisms is missing. Here, we investigated metabolic effects of the novel non\u2010steroidal MRA finerenone (FIN) in a mouse model of high\u2010fat diet (HFD)\u2010induced obesity and the signaling pathways activated by MR antagonism at level of interscapular brown adipose tissue (iBAT). C57BL\/6J male mice were fed a normal diet or a HFD (with60%\n                    <jats:italic>\u00a0<\/jats:italic>\n                    kcal\u00a0from fat) containing or not FIN for 3\u00a0months. Metabolic parameters, adipose tissue morphology, gene and protein expression analysis were assessed. We also used brown adipocyte cultures (T37i cells) to investigate the effects of FIN\u2010mediated MR antagonism upon lipid and mitochondrial metabolism. HFD\u00a0+\u00a0FIN\u2010treated mice showed improved glucose tolerance together with increased multilocularity and higher expression of thermogenic markers at the level of iBAT, without differences in white adipose depots, suggesting an iBAT\u2010specific effect of FIN. Mechanistically, FIN increased activation of AMP\u2010activated protein kinase which, in turn, stimulated adipose triglyceride lipase activation, with subsequent increased expression of uncoupling protein\u20101 in brown adipocytes.\n                  <\/jats:p>","DOI":"10.1096\/fj.202000164r","type":"journal-article","created":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T20:55:54Z","timestamp":1596142554000},"page":"12450-12465","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["The novel non\u2010steroidal MR antagonist finerenone improves metabolic parameters in high\u2010fat diet\u2010fed mice and activates brown adipose tissue via\u00a0AMPK\u2010ATGL pathway"],"prefix":"10.1096","volume":"34","author":[{"given":"Vincenzo","family":"Marzolla","sequence":"first","affiliation":[{"name":"Laboratory of Cardiovascular Endocrinology IRCCS San Raffaele Pisana Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Feraco","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Endocrinology IRCCS San Raffaele Pisana Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Gorini","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Endocrinology IRCCS San Raffaele Pisana Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Mammi","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Endocrinology IRCCS San Raffaele Pisana Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Marrese","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Endocrinology IRCCS San Raffaele Pisana Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Mularoni","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopedic Sciences \u2010 Section of Histology and Medical Embryology Sapienza University of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Boitani","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopedic Sciences \u2010 Section of Histology and Medical Embryology Sapienza University of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Lomb\u00e8s","sequence":"additional","affiliation":[{"name":"INSERM UMR_S U1185, Fac Med Paris Sud, Univ. 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