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This version published online on June 30, 2009
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2009-0571
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Submitted on March 16, 2009
Accepted on June 19, 2009

Uncoupling Protein-1 and related mRNAs in Human Epicardial and Other Adipose Tissues: Epicardial Fat functioning as Brown Fat

Harold S. Sacks M.D.*, John N. Fain Ph.D., Ben Holman M.D., Paramjeet Cheema MS, Aron Chary MA, Frank Parks M.D., James Karas MS, Robert Optican M.D., Suleiman W. Bahouth Ph.D., Edward Garrett M.D., Rodney Y. Wolf M.D., Russell A. Carter M.D., Todd Robbins MD, David Wolford MD, and Joseph Samaha MD

Departments of Medicine; Molecular Sciences; Radiology; Pharmacology; College of Medicine, University of Tennessee Health Science Center Memphis, TN 38163, USA; The Baptist Heart Institute; and Department of Radiology; Baptist Memorial Hospital, Memphis, TN, 38120

* To whom correspondence should be addressed. E-mail: hsacks{at}hotmail.com.

Context. Uncoupling protein-1 [UCP-1] is the inner mitochondrial membrane protein that is a specific marker for and mediator of non-shivering 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-missing16 [PRDM16] and peroxisome-proliferator-activated receptor {gamma} co-activator-1{alpha} [PGC-1{alpha}] in epicardial, substernal and subcutaneous thoracic, abdominal and leg fat.

Setting. Tertiary care hospital cardiac center.

Patients. Coronary artery bypass (n = 44) and valve replacement (n = 6).

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 subcutaneous fat. Epicardial fat UCP-1 expression decreased with age, increased with BMI, 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-1{alpha} expression was 2 fold greater in epicardial than subcutaneous fat. Epicardial fat UCP-1, PRDM16 and PGC1-{alpha} mRNAs were similar in diabetics treated with thiazolidenediones compared to diabetics not treated with thiazolidenediones.

Conclusion: Since 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.


Key words: Epicardial fat • Uncoupling protein-1 • Brown Fat







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