title: Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy.
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.
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Robrecht
authors.initials: R
authors.lastname: Thoonen
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA; DHU Ageing Thorax Vessels Blood, Inserm Unit 955 Team 08, Faculté de Medecine de Créteil, Hôpital Henri Mondor, AP-HP, Créteil, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Ernande
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA; Department of Ultrasound, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA; Department of Anesthesia and Critical Pain, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Nagasaka
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Yao
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Miranda-Bezerra
authors.affiliation: Department of Anesthesia and Critical Pain, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Chan
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Anesthesia and Critical Pain, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Chao
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Marcello
authors.initials: M
authors.lastname: Panagia
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Sosnovik
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Dheeraj
authors.initials: D
authors.lastname: Puppala
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Antonis A
authors.initials: AA
authors.lastname: Armoundas
authors.affiliation: Department of Anesthesia and Critical Pain, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Allyson
authors.initials: A
authors.lastname: Hindle
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA; Department of Anesthesia and Critical Pain, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bloch
authors.affiliation: Department of Anesthesia and Critical Pain, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Buys
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA. Electronic address: marielle@crosbie.com.
authors.forename: Marielle
authors.initials: M
authors.lastname: Scherrer-Crosbie
mesh_terms: D002001:Adipose Tissue, Brown / Q000502:physiology* / Q000637:transplantation; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D009202:Cardiomyopathies / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D002316:Cardiotonic Agents / Q000378:metabolism; D002395:Catecholamines / Q000008:administration & dosage / Q000009:adverse effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000187:drug effects; D006333:Heart Failure / Q000150:complications / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D007473:Ion Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016019:Survival Analysis; D014463:Ultrasonography; D000071256:Uncoupling Protein 1; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D015415:Biomarkers; D002316:Cardiotonic Agents; D002395:Catecholamines; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D007545:Isoproterenol
keywords: Brown adipose tissue; Cardioprotection; Heart failure; Isoproterenol; Uncoupling protein 1