Physiological Relationships of Uncoupling Protein-2 Gene Expression in Human Adipose Tissue in Vivo1
Jonathan H. Pinkney,
Olivier Boss,
George A. Bray,
Karen Bulmer,
Simon W. Coppack and
Vidya Mohamed-Ali
Pennington Biomedical Research Center, Louisiana State University
(J.H.P., G.A.B.), Baton Rouge, Louisiana 70808-4124; Department of
Medicine, University of Bristol, Bristol Royal Infirmary (J.H.P.),
Bristol, United Kingdom BS2 8HW; Faculty of Medicine, Medical
Biochemistry, University of Geneva (O.B.), 1211 Geneva 4, Switzerland;
and Department of Medicine, University College London Medical School,
Whittington Hospital (K.B., S.W.C., V.M.-A.), London, United Kingdom
N19 3UA
Address all correspondence and requests for reprints to: Dr. Jonathan H. Pinkney, University of Bristol, Department of Medicine, Research Centre for Neuroendocrinology, Bristol Royal Infirmary, Marlborough Street, Bristol BS2 8HW, United Kingdom. E-mail:
j.pinkney{at}bris.ac.uk
The physiological significance of changes in uncoupling protein-2
(UCP-2)gene expression is controversial. In this study we investigated
thebiochemical and functional correlates of UCP-2 gene expressionin
sc abdominal adipose tissue in humans in vivo. UCP-2
messengerribonucleic acid expression was quantified by nuclease
protectionin adipose tissue from lean and obese humans in both the
fastingand postprandial states. Plasma fatty acids, insulin, and
leptinwere all determined in paired samples from the superficial
epigastricvein and radial artery, and local production rates were
calculatedfrom 133Xe washout. In the fasting state UCP-2
expression correlatedinversely with body mass index (r = -0.45;
P = 0.026), percentbody fat (r = -0.41;
P = 0.05), plasma insulin (r = -0.47;
P= 0.02), epigastric venous fatty acids (r =
-0.45; P = 0.04),and leptin (r = -0.50;
P = 0.018). UCP-2 expression remainedinversely
related with plasma leptin after controlling for percentbody (r =
-0.45; P = 0.038). At 2 or 4 h
postprandially, therewere no significant relationships between UCP-2
expression andbiochemical parameters. In conclusion, 1) UCP-2
messenger ribonucleicacid expression in sc adipose tissue is inversely
related toadiposity and independently linked to local plasma leptin
levels;and 2) UCP-2 expression is not acutely regulated by food
intake,insulin, or fatty acids. Reduced UCP-2 expression may be a
maladaptiveresponse to sustained energy surplus and could contribute
tothe pathogenesis and maintenance of obesity.
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