Thoonen, RobrechtErnande, LauraCheng, JuanNagasaka, YasukoYao, VincentMiranda-Bezerra, AlexandreChen, ChanChao, WeiPanagia, MarcelloSosnovik, DavidPuppala, DheerajArmoundas, AntonisHindle, AllysonBloch, KennethBuys, EmmanuelScherrer-Crosbie, Marielle2016-12-212015Thoonen, Robrecht, Laura Ernande, Juan Cheng, Yasuko Nagasaka, Vincent Yao, Alexandre Miranda-Bezerra, Chan Chen, et al. 2015. Functional Brown Adipose Tissue Limits Cardiomyocyte Injury and Adverse Remodeling in Catecholamine-Induced Cardiomyopathy. Journal of Molecular and Cellular Cardiology 84: 202–211. doi:10.1016/j.yjmcc.2015.05.002.0022-2828http://nrs.harvard.edu/urn-3:HUL.InstRepos:29729434Brown adipose tissue (BAT) has well recognized thermogenic properties mediated by uncoupling protein 1 (UCP1); more recently, BAT has been demonstrated to modulate cardiovascular risk factors. To investigate whether BAT also affects myocardial injury and remodeling, UCP1-deficient (UCP1−/−) mice, which have dysfunctional BAT, were subjected to catecholamine-induced cardiomyopathy. At baseline, there were no differences in echocardiographic parameters, plasma cardiac troponin I (cTnI) or myocardial fibrosis between wild-type (WT) and UCP1−/− mice. Isoproterenol infusion increased cTnI and myocardial fibrosis and induced left ventricular (LV) hypertrophy in both WT and UCP1−/− mice. UCP1−/− mice also demonstrated exaggerated myocardial injury, fibrosis, and adverse remodeling, as well as decreased survival. Transplantation of WT BAT to UCP1−/− mice prevented the isoproterenol-induced cTnI increase and improved survival, whereas UCP1−/− BAT transplanted to either UCP1−/− or WT mice had no effect on cTnI release. After 3 days of isoproterenol treatment, phosphorylated AKT and ERK were lower in the LV's of UCP1−/− mice than in those of WT mice. Activation of BAT was also noted in a model of chronic ischemic cardiomyopathy, and was correlated to LV dysfunction. Deficiency in UCP1, and accompanying BAT dysfunction, increases cardiomyocyte injury and adverse LV remodeling, and decreases survival in a mouse model of catecholamine-induced cardiomyopathy. Myocardial injury and decreased survival are rescued by transplantation of functional BAT to UCP1−/− mice, suggesting a systemic cardioprotective role of functional BAT. BAT is also activated in chronic ischemic cardiomyopathy.en-USbrown adipose tissueuncoupling protein 1isoproterenolcardioprotectionheart failureJournal Article2016-12-2110.1016/j.yjmcc.2015.05.002