Uncoupling Protein-1 and Related Messenger Ribonucleic Acids in Human Epicardial and Other Adipose Tissues: Epicardial Fat Functioning as Brown Fat

Abstract

Context: Uncoupling protein-1 (UCP-1) is the inner mitochondrial membrane protein that is a specific marker for and mediator of nonshivering thermogenesis in brown adipocytes. Objective: This study was performed to better understand the putative thermogenic function of human epicardial fat. Design: We measured the expression of UCP-1 and brown adipocyte differentiation transcription factors PR-domain-missing 16 (PRDM16) and peroxisome-proliferator-activated receptor γ co-activator-1α (PGC-1α) in epicardial, substernal, and sc thoracic, abdominal, and leg fat. Setting: The study was conducted at a tertiary care hospital cardiac center. Patients: Forty-four patients had coronary artery bypass surgery, and six had heart valve replacement. Interventions: Fat samples were taken at open heart surgery. Results: UCP-1 expression was 5-fold higher in epicardial fat than substernal fat and barely detectable in sc fat. Epicardial fat UCP-1 expression decreased with age, increased with body mass index, was similar in women and men and patients on and not on statin therapy, and showed no relationship to epicardial fat volume or waist circumference. UCP-1 expression was similar in patients without and with severe coronary atherosclerosis and metabolic syndrome or type 2 diabetes. PRDM16 and PGC-1α expression was 2-fold greater in epicardial than sc fat. Epicardial fat UCP-1, PRDM16, and PGC1-α mRNAs were similar in diabetics treated with thiazolidinediones compared to diabetics not treated with thiazolidinediones. Conclusion: Because UCP-1 is expressed at high levels in epicardial fat as compared to other fat depots, the possibility should be considered that epicardial fat functions like brown fat to defend the myocardium and coronary vessels against hypothermia. This process could be blunted in the elderly. Since uncoupling protein-1 is highly expressed in epicardial fat compared to other fat depots, epicardial fat might function like brown fat, defending the heart against hypothermia.