Uncoupling protein-2 (UCP2) and uncoupling protein-3 (UCP3) expression in adipose tissue and skeletal muscle in humans

Western blots detected uncoupling protein 3 (UCP3) in skeletal-muscle mitochondria from wild-type but not UCP3 knock-out mice. Calibration with purified recombinant UCP3 showed that mouse and rat skeletal muscle contained 0.14μg of UCP3/mg of mitochondrial protein. This very low UCP3 content is 200–700-fold less than the concentration of UCP1 in brown-adipose-tissue mitochondria from warm-adapted hamster (24–84μg of UCP1/mg of mitochondrial protein). UCP3 was present in brown-adipose-tissue mitochondria from warm-adapted rats but was undetectable in rat heart mitochondria. We expressed human UCP3 in yeast mitochondria at levels similar to, double and 7-fold those found in rodent skeletal-muscle mitochondria. Yeast mitochondria containing UCP3 were more uncoupled than empty-vector controls, particularly at concentrations that were 7-fold physiological. However, uncoupling by UCP3 was not stimulated by the known activators palmitate and superoxide; neither were they inhibited by GDP, suggesting that the observed uncoupling was a property of non-native protein. As a control, UCP1 was expressed in yeast mitochondria at similar concentrations to that of UCP3 and at up to 50% of the physiological level of UCP1. Low levels of UCP1 gave palmitate-dependent and GDP-sensitive proton conductance but higher levels of UCP1 caused an additional GDP-insensitive uncoupling artifact. We conclude that the uncoupling of yeast mitochondria by high levels of UCP3 expression is entirely an artifact and provides no evidence for any native uncoupling activity of the protein.

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Uncoupling Protein-2 and -3 Messenger Ribonucleic Acids in Adipose Tissue and Skeletal Muscle of Healthy Males: Variability, Factors Affecting Expression, and Relation to Measures of Metabolic Rate

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.85.5.1975 ◽

2000 ◽

Vol 85 (5) ◽

pp. 1975-1983 ◽

Cited By ~ 7

Author(s):

M. Boivin

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Metabolic Rate ◽

Uncoupling Protein ◽

Uncoupling Protein 2 ◽

Ribonucleic Acids ◽

Factors Affecting ◽

Healthy Males

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Differential Regulation of Uncoupling Protein-2 and Uncoupling Protein-3 Gene Expression in Brown Adipose Tissue during Development and Cold Exposure

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.1998.8088 ◽

1998 ◽

Vol 243 (1) ◽

pp. 224-228 ◽

Cited By ~ 39

Author(s):

M.Carmen Carmona ◽

Angel Valmaseda ◽

Sonia Brun ◽

Octavi Viñas ◽

Teresa Mampel ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Cold Exposure ◽

Uncoupling Protein ◽

Differential Regulation ◽

Uncoupling Protein 2 ◽

Uncoupling Protein 3 ◽

Brown Adipose

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Uncoupling protein 2 and 3 in marsupials: identification, phylogeny, and gene expression in response to cold and fasting in Antechinus flavipes

Physiological Genomics ◽

10.1152/physiolgenomics.00165.2003 ◽

2004 ◽

Vol 17 (2) ◽

pp. 130-139 ◽

Cited By ~ 23

Author(s):

Martin Jastroch ◽

Kerry Withers ◽

Martin Klingenspor

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Adipose Tissue ◽

Tissue Specificity ◽

Striated Muscle ◽

Uncoupling Protein ◽

Uncoupling Protein 2 ◽

Reading Frame ◽

Amino Acid Peptide ◽

Ucp3 Gene

We searched for the presence of uncoupling protein genes so far unknown in marsupials and monotremes and identified uncoupling protein 2 (UCP2) and UCP3 full-length cDNAs in libraries constructed from the marsupials Antechinus flavipes and Sminthopsis macroura. Marsupial UCP2 is 89–90% identical to rodent UCP2, whereas UCP3 exhibits 80% identity to mouse UCP3. A phylogenetic tree including all known UCPs positions the novel marsupial UCP2 and UCP3 at the base of the mammalian orthologs. In the 5′-untranslated region of UCP2 a second open reading frame encoding for a 36-amino acid peptide was identified which is highly conserved in all vertebrate UCP2 transcripts. Analysis of tissue specificity in A. flavipes with homologous cDNA probes revealed ubiquitous presence of UCP2 mRNA and striated muscle specificity of UCP3 mRNA resembling the known expression pattern in rodents. Neither UCP2 nor UCP3 gene expression was stimulated in adipose tissue and skeletal muscle of cold exposed A. flavipes. However, UCP3 mRNA expression was upregulated 6-fold in heart and 2.5-fold in skeletal muscle as reported for rodents in response to fasting. Furthermore, UCP3 mRNA seems to be coregulated with PDK4 mRNA, indicating a relation to enhanced lipid metabolism. In contrast, UCP2 gene expression was not regulated in response to fasting in adipose tissue and skeletal muscle but was diminished in the lung and increased in adipose tissue. Taken together, the sequence analysis, tissue specificity and physiological regulation suggest a conserved function of UCP2 and UCP3 during 130 million years of mammalian evolution.

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Exercise induces an increase in muscle UCP3 as a component of the increase in mitochondrial biogenesis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00316.2002 ◽

2003 ◽

Vol 284 (1) ◽

pp. E96-E101 ◽

Cited By ~ 37

Author(s):

Terry E. Jones ◽

Keith Baar ◽

Edward Ojuka ◽

May Chen ◽

John O. Holloszy

Keyword(s):

Skeletal Muscle ◽

Mitochondrial Biogenesis ◽

Protein Concentration ◽

Uncoupling Protein ◽

Exercise Bout ◽

Mitochondrial Marker ◽

Marker Proteins ◽

Uncoupling Protein 3 ◽

Exercise Induced ◽

Ucp3 Expression

Previous studies have indicated that exercise acutely induces large increases in uncoupling protein-3 (UCP3) in skeletal muscle, whereas endurance training results in marked decreases in muscle UCP3. Because UCP3 expression appears to be regulated by the same mechanism as other mitochondrial constituents, it seemed unlikely that exercise would result in such large and divergent changes in mitochondrial composition. The purpose of this study was to test the hypothesis that major changes in UCP3 protein concentration do not occur independently of mitochondrial biogenesis and that UCP3 increases as a component of the exercise-induced increase in mitochondria. We found a large increase in UCP3 mRNA immediately and 3 h after a bout of swimming. UCP3 protein concentration was increased ∼35% 18 h after a single exercise bout, ∼63% after 3 days, and ∼84% after 10 days of exercise. These increases in UCP3 roughly paralleled those of other mitochondrial marker proteins. Our results are consistent with the interpretation that endurance exercise induces an adaptive increase in mitochondria that have a normal content of UCP3.

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