Uncoupling protein-1 and related messenger ribonucleic acids in human epicardial and other adipose tissues: epicardial fat functioning as brown fat.
BACKGROUND
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.


METHODS
We measured the expression of UCP-1 and brown adipocyte differentiation transcription factors PR-domain-missing 16 (PRDM16) and peroxisome-proliferator-activated receptor gamma co-activator-1 alpha (PGC-1 alpha) in epicardial, substernal, and sc thoracic, abdominal, and leg fat.


METHODS
The study was conducted at a tertiary care hospital cardiac center.


METHODS
Forty-four patients had coronary artery bypass surgery, and six had heart valve replacement.


METHODS
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-1 alpha expression was 2-fold greater in epicardial than sc fat. Epicardial fat UCP-1, PRDM16, and PGC1-alpha mRNAs were similar in diabetics treated with thiazolidinediones compared to diabetics not treated with thiazolidinediones.


CONCLUSIONS
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.
Sacks
Harold S
HS
Department of Medicine, College of Medicine, University of Tennessee Health Science Center Memphis, Tennessee 38163, USA. hsacks@hotmail.com
Fain
John N
JN
Holman
Ben
B
Cheema
Paramjeet
P
Chary
Aron
A
Parks
Frank
F
Karas
James
J
Optican
Robert
R
Bahouth
Suleiman W
SW
Garrett
Edward
E
Wolf
Rodney Y
RY
Carter
Russell A
RA
Robbins
Todd
T
Wolford
David
D
Samaha
Joseph
J
D000273:Adipose Tissue / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000368:Aged; D003324:Coronary Artery Disease / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D010496:Pericardium / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000032:analysis; D014157:Transcription Factors / Q000235:genetics*; D000071256:Uncoupling Protein 1
D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; C486497:PPARGC1A protein, human; C416371:PRDM16 protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D014157:Transcription Factors; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1