Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy. (July 2015)

• Record Type: Journal Article
• Authors: Thoonen, Robrecht; Ernande, Laura; Cheng, Juan; Nagasaka, Yasuko; Yao, Vincent; Miranda-Bezerra, Alexandre; Chen, Chan; Chao, Wei; Panagia, Marcello; Sosnovik, David E.; Puppala, Dheeraj; Armoundas, Antonis A.; Hindle, Allyson; Bloch, Kenneth D.; Buys, Emmanuel S.; Scherrer-Crosbie, Marielle
• Is Part Of: Journal of molecular and cellular cardiology. Volume 84(2015:Jul.)
• Page Start: 202
• Page End: 211
• Publication Date: 2015-07
• Subjects: BAT brown adipose tissue -- UCP1 uncoupling protein 1 -- UCP1−/− UCP1-deficient -- LV left ventricle -- WT wild-type -- H/R wall thickness/LV radius -- LVMI LV mass index -- cTnI cardiac troponin I -- MI myocardial infarct -- LVEDD LV end-diastolic diameter -- LVESD LV end-systolic diameter -- PWT posterior wall thickness -- IVS interventricular septal thickness -- AWT anterior wall thickness -- LVEF LV ejection fraction -- SBP systolic blood pressure -- DBP diastolic blood pressure -- GTT glucose tolerance test -- ITT insulin tolerance test -- FABP3 fatty acid binding protein 3 -- MYL3 myosin light chain 3; Brown adipose tissue -- Uncoupling protein 1 -- Isoproterenol -- Cardioprotection -- Heart failure; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2015.05.002
• Languages: English
• ISSNs: 0022-2828

Abstract

Abstract: Brown 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. Highlights: Brown adipose tissue (BAT) modulates cardiovascular risk factors. UCP1-deficiency exacerbates isoproterenol-induced myocardial injury. BAT transplantation in UCP1 −/− mice is cardioprotective.