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We investigated responses to the MR antagonists spironolactone (spiro; 20 mg\/kg\/d) and drospirenone (DRSP; 6 mg\/kg\/d) in C57BL\/6 mice fed a high\u2010fat (HF) diet for 90 d. DRSP and spiro curbed HF diet\u2010induced impairment in glucose tolerance, and prevented body weight gain and white fat expansion. Notably, either MR antagonist induced up\u2010regulation of brown adipocyte\u2010specific transcripts and markedly increased protein levels of uncoupling protein 1 (UCP1) in visceral and inguinal fat depots when compared with the HF diet group. Positron emission tomography and magnetic resonance spectroscopy confirmed acquisition of brown fat features in WAT. Interestingly, MR antagonists markedly reduced the autophagic rate both in murine preadipocytes\n                    <jats:italic>in vitro<\/jats:italic>\n                    (10\n                    <jats:sup>\u20105<\/jats:sup>\n                    M) and in WAT depots\n                    <jats:italic>in vivo<\/jats:italic>\n                    , with a concomitant increase in UCP1 protein expression. Moreover, the autophagy repressor bafilomycin A1 (10\n                    <jats:sup>\u20108<\/jats:sup>\n                    M) mimicked the effect of MR antagonists, increasing UCP1 protein expression in primary preadipocytes. Hence, we showed that adipocyte MR regulates brown remodeling of WAT through a modulation of autophagy. These results provide a rationale for the use of MR antagonists to prevent the adverse metabolic consequences of adipocyte dysfunction.\u2014Armani, A., Cinti, F., Marzolla, V., Morgan, J., Cranston, G. A., Antelmi, A., Carpinelli, G., Canese, R., Pagotto, U., Quarta, C., Malorni, W., Matarrese, P., Marconi, M., Fabbri, A., Rosano, G., Cinti, S., Young, M. J., Caprio, M. Mineralocorticoid receptor antagonism induces browning of white adipose tissue through impairment of autophagy and prevents adipocyte dysfunction in high\u2010fat\u2010diet\u2010fed mice.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    28, 3745\u20133757 (2014).\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.13-245415","type":"journal-article","created":{"date-parts":[[2014,5,7]],"date-time":"2014-05-07T21:22:34Z","timestamp":1399497754000},"page":"3745-3757","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":161,"title":["Mineralocorticoid receptor antagonism induces browning of white adipose tissue through impairment of autophagy and prevents adipocyte dysfunction in high\u2010fat\u2010diet\u2010fed mice"],"prefix":"10.1096","volume":"28","author":[{"given":"Andrea","family":"Armani","sequence":"first","affiliation":[{"name":"Laboratory of Cardiovascular Endocrinology Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Pisana Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Cinti","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Endocrinology Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Pisana Rome Italy"},{"name":"Department of Experimental and Clinical Medicine, Center for the Study of Obesity United Hospitals University of Ancona Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Marzolla","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Endocrinology Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Pisana Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Morgan","sequence":"additional","affiliation":[{"name":"Monash Institute of Medical Research\u2010Prince Henry's Institute (MIMR\u2010PHI) Medical Research Institute Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg A.","family":"Cranston","sequence":"additional","affiliation":[{"name":"Monash Institute of Medical Research\u2010Prince Henry's Institute (MIMR\u2010PHI) Medical Research Institute Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Antelmi","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Endocrinology Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Pisana Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Carpinelli","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neurosciences Istituto Superiore di Sanit\u00e0 Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Canese","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neurosciences Istituto Superiore di Sanit\u00e0 Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uberto","family":"Pagotto","sequence":"additional","affiliation":[{"name":"Endocrinology Unit Alma Mater University of Bologna Bologna Italy"},{"name":"Center for Applied Biomedical Research, Department of Medical and Surgical Sciences S. 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Orsola\u2010Malpighi Hospital, Alma Mater University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Malorni","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Research and Medicine Evaluation Istituto Superiore di Sanit\u00e0 Rome Italy"},{"name":"San Raffaele Institute Sulmona L'Aquila Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Matarrese","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Research and Medicine Evaluation Istituto Superiore di Sanit\u00e0 Rome Italy"},{"name":"Center of Integrated Metabolomics Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Marconi","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Research and Medicine Evaluation Istituto Superiore di Sanit\u00e0 Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Fabbri","sequence":"additional","affiliation":[{"name":"Department of Medicina dei Sistemi, Endocrinology Unit S. 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