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 catecholamineinduced 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,

Eicosapentaenoic Acid Reduces Adiposity, Glucose Intolerance and Increases Oxygen Consumption Independently of Uncoupling Protein 1

“…These findings are supported by results from Thoonen et al. showing that glucose intolerance in UCP1 KO mice was restored by BAT transplantation . In line with these studies, we demonstrated that HF‐fed KO mice exhibited impaired glucose clearance compared to WT mice.…”

A2A Receptor Activation Attenuates Hypertensive Cardiac Remodeling via Promoting Brown Adipose Tissue-Derived FGF21

“…IBAT Surgical Depletion Mice was exposed to euthanasia by 1.5% pentobarbital Sodium (85-100 mg/kg body weight) and the iBAT was surgically depleted as previously described (Thoonen et al, 2015). Mice that were sham operated underwent the same procedure, their iBAT pad was located, exposed, and then been closed.…”

Circulating neuregulin 4 levels are inversely associated with subclinical cardiovascular disease in obese adults

“…However, little is currently understood about the role of Nrg4 in the pathophysiology of CVD. It has been proposed that brown adipose tissues is capable of modulating cardiovascular risk factors and atherosclerosis development182425 thus, these data have implications that brown fat-enriched secreted factor Nrg4 may be involved in crosstalk between brown adipose tissue and CVD.…”