Skeletal muscle UCP2 and UCP3 expression in trained and untrained male subjects

Schrauwen, Patrick; Troost, Freddy J.; Xia, Jing; Ravussin, Éric; Saris, Wim H. M.

doi:10.1038/sj.ijo.0801026

Cited by 77 publications

(91 citation statements)

References 24 publications

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“…25 The other muscle samples were quickly frozen and stored in liquid nitrogen for later UCP2, UCP3, b-actin and cytochrome b mRNA analysis. 16 Immediately prior to analysis, part of the latter sample was weighed, homogenised and then freeze -thawed twice. The homogenate was then centrifuged and the supernatant was analysed for citrate synthase (CS) activity using spectrophotometric detection.…”

Section: Slow Component Of V á O 2 Kineticsmentioning

confidence: 99%

“…13 Both uncouple mitochondrial oxidative phosphorylation, 14,15 which results in the production of heat without an increase in ATP production. Additionally, UCP3 mRNA has been inversely correlated with mechanical efficiency at low submaximal steady-state intensities 16 and found to be lower in endurance-trained rodents 17 and humans 16 compared to normal controls. The possibility, however, that both mitochondrial enzyme activity and UCP3 might have an adverse role in muscle efficiency of exercising healthy individuals during high intensity submaximal exercise has never been addressed.…”

Section: Introductionmentioning

confidence: 99%

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Slow component of V̇O2 kinetics: the effect of training status, fibre type, UCP3 mRNA and citrate synthase activity

et al. 2002

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OBJECTIVE:In healthy individuals performing constant-load exercise at intensities above the lactate threshold a secondary rise in pulmonary oxygen uptake (V O 2 ) occurs. V O 2 reaches a maximum and exhaustion rapidly prevails for a range of work rates lower than the maximal work rate achieved during a conventional rapid-incremental test. This phenomenon is called the slow component (SC) of V O 2 kinetics and represents an increase in V O 2 without an increase in work rate. Although still under debate, the magnitude of the SC is believed to be associated with the percentage of type II muscle fibres and their recruitment. In this study we investigated the relationship between the magnitude of the relative SC, citrate synthase activity, UCP2 and UCP3 mRNA levels and muscle fibre composition in both endurance-trained and recreationally active subjects. METHOD: The magnitude of the relative SC was measured in 12 endurance-trained (Tr) and 15 recreationally active (RA) male subjects. The magnitude of the relative SC was determined as the difference between the end-exercise V O 2 and 3 min V O 2 divided by the difference between end-exercise V O 2 and baseline V O 2 . UCP2 and UCP3 mRNA expression in the vastus lateralis was measured by RT-PCR with b-actin mRNA used as an internal control. These values were also normalized against cytochromeb mRNA to control for training induced changes in mitochondria when comparing the Tr and RA groups. Type I, IIa and IIx skeletal muscle fibre composition was determined using a routine myosin ATPase histochemical staining technique. Citrate synthase (CS) activity was measured using spectrophotometric detection. RESULTS:The magnitude of the relative SC of the Tr group had the highest correlation with citrate synthase activity (r ¼ 7 0.90, P < 0.001) and that of the RA group with V O 2 peak (r ¼ 7 0.68, P < 0.01). For the Tr group other correlations with the magnitude of the relative SC included UCP3 mRNA levels (r ¼ 0.69, P < 0.05) and the percentage of type I fibres (r ¼ 7 0.58, P < 0.05), while for the RA group they included UCP3 mRNA (r ¼ 0.58, P < 0.05) and the percentage of type IIa muscle fibres (r ¼ 0.59, P < 0.05). The Tr subjects had a lower relative SC (P ¼ 0.04) and a lower expression of UCP2 (P ¼ 0.04), and UCP3 mRNA (P ¼ 0.01) than the RA subjects. When the groups were combined the magnitude of the relative SC correlated with UCP3 mRNA (r ¼ 0.70, P < 0.01), percentage of type IIa muscle fibres (r ¼ 0.60, P < 0.01) and V O 2 peak (r ¼ 7 0.73, P < 0.01). Additionally UCP3 mRNA correlated with the percentage of type IIa muscle fibres (r ¼ 0.63, P < 0.001). CONCLUSION: Citrate synthase activity and V O 2 peak are indicators of aerobic fitness. The high negative correlations between the magnitude of the relative SC and citrate synthase activity and V O 2 peak, of the Tr and RA subjects, respectively, suggests that the magnitude of the relative SC is inversely correlated with aerobic fitness. Additionally the correlations between UCP3 mRNA and the magnitude of the relative SC...

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Section: Slow Component Of V á O 2 Kineticsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Slow component of V̇O2 kinetics: the effect of training status, fibre type, UCP3 mRNA and citrate synthase activity

et al. 2002

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“…Similarly, Schrauwen et al. (29) reported that endurance-trained men had significantly reduced UCP3 mRNA levels in quadriceps muscles compared with untrained men and that UCP3 mRNA was negatively correlated with maximal oxygen uptake capacity in these subjects.Taken together, the results of these studies have led to the hypotheses that the "acute regulation of UCP3 gene expression has immediate and functionally important consequences" (37), whereas the decrease in UCP3 mRNA with long-term training results in an increase in the metabolic efficiency of muscle (6,30). These hypotheses imply that exercise results in major Address for reprint requests and other correspondence: J. O.…”

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confidence: 99%

“…Taken together, the results of these studies have led to the hypotheses that the "acute regulation of UCP3 gene expression has immediate and functionally important consequences" (37), whereas the decrease in UCP3 mRNA with long-term training results in an increase in the metabolic efficiency of muscle (6,30). These hypotheses imply that exercise results in major changes in mitochondrial composition, with a great short-term increase in UCP3 and a large long-term decrease in the amount of UCP3 relative to the other mitochondiral constituents.…”

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confidence: 99%

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

Jones

Baar

Ojuka

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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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 ϳ35% 18 h after a single exercise bout, ϳ63% after 3 days, and ϳ84% 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. gene expression; cytochrome c; cytochrome oxidase; skeletal muscle THE MITCHONDRIAL PROTEIN UCP3 was identified on the basis of its homology with the uncoupling protein-1 (UCP1) present in brown adipose tissue (14). It has been proposed on the basis of its homology with UCP1 that UCP3 also functions as an uncoupling protein (5, 14). Furthermore, some investigators have interpreted the results of studies of the heterologous expression of UCP3 in yeast (36) and of overexpression or knockout of UCP3 in transgenic mice (8, 9, 34) as providing evidence for uncoupling.UCP3 is expressed primarily in skeletal muscle (14). Because of its possible role in energy metabolism, a number of investigators have studied the adaptive response of UCP3 in skeletal muscle to exercise (11,23,29,33,37). reported that UCP3 mRNA was increased sevenfold in skeletal muscle of mice 3 h after a single bout of treadmill running and 16-fold 3 h after exercise in mice that had been trained for 3 wk by swimming. They speculated that "upregulation of UCP3 mRNA may be a defense mechanism against extra energy supply to consume extra energy in skeletal muscle." Similarly, Zhou et al. (37) reported that UCP3 mRNA was increased approximately sevenfold immediately after a 200-min-long bout of swimming. A similar response was seen after a bout of treadmill running. They also reported that UCP3 protein concentration was increased 3.5-fold immediately after 100 min of treadmill running and 5.6-fold immediately after 200 min of running (37). In studies in humans, Pilegaard et al. (23) found an ϳ2.5-fold increase in UCP3 mRNA 4 h after a 4-h bout of cycling, and Schrauwen et al. (29) reported an approximately twofold increase in UCP3 mRNA 4 h after exercise in men who performed cycle exercise for 2 h in the fasting state.Although there were differences in the time course and magnitudes of the increases, all of the studies on the acute effect of ex...

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“…In humans, UCP3 mRNA (50,51) and protein levels (43) have been shown to be lower in endurance trained cyclists as compared to healthy control subjects. Additionally, we have recently observed that the UCP3 protein content is lower in all fiber types of endurance trained when compared to healthy individuals.…”

Section: Regulation Of Energy Expenditurementioning

confidence: 98%

Old and new determinants in the regulation of energy expenditure

Russell¹,

Giacobino²

2002

J Endocrinol Invest

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ABSTRACT. Bw gain is controlled by energy intake on one hand and expenditure on the other. The components of energy expenditure are basal metabolism, exercise induced thermogenesis and adaptive UNCOUPLING PROTE/N-1 (UCP1)In rodents, brown adipose tissue (BAT) is an important site of adaptive thermogenesis. Cold exposure has for long been known to induce, via stimulation of the sympathetic nervous system, an increase in BAT thermogenesis referred to as adaptive cold-induced thermogenesis (CIT), (1). Furthermore, it has been observed that voluntary overeating induced in rats by the administration of a palatable, so-called "cafeteria" diet also induced an increase in BAT thermogenesis which was called adaptive diet-induced thermogenesis (OIT) (2).The main producer of heat in BAT is the uncoupling protein-1 (UCP1). This mitochondria inner membrane protein uncouples oxidative phosphorylation by dissipating the proton gradient generated by the re-oxidation of NAOH H+ in the respiratory chain. The UCP1-mediated proton transport requires the presence of fatty acids and is specificalIy inhibited by purine di-and triphosphate nucleotides (3). The consequence of UCP1 activity is a decrease in the amount of ATP formed by the ATP synthase and energy dissipation as heat. UCP1 knockout mice were generated and they were unable to maintain their body temperature upon cold exposure but did not become obese (4).These data confirmed the importance of UCP1 in Key-words: ßTadrenoceptor. uncoupling CIT and suggested that, in UCP1 knockout mice, alternative mechanisms for maintaining body mass wh ich could not protect against the cold were turned on, In humans, BAT is present in newborn babies and decreases in 4-6 months after birth (5, 6). It is therefore generally believed that there is no UCP1 in human adults. THE ßTADRENOCEPTOR -UCP1 AX/SThe family of the ß-adrenoceptors were considered to consist of ß1-and ß-rsubtypes until1989 when a third subtype was cloned (7). This third subtype called the ß3-adrenoceptor was found to be the predominant ß-subtype in rodent BAT and white adipose tissue (WAT) (8,9). When the BAT sympathetic nervous system activity is increased by cold exposure or overfeeding, the stimulatory effect on UCP1 activity and expression is therefore mediated essentially by the ß3-adrenoceptor (9). Therefore, the ß3-adrenoceptor-UCP1-axis is a major determinant of rodent adaptive thermogenesis, The ß3-adrenoceptor was found to be down-regulated in obese fa/fa Zucker rat BAT and WAT (8) and in obese ob/ob mouse adipose tissues compa red to lean animals (10). In ß3-adrenoceptor knockout mice, the capacity to adapt to a cold environment was fully preserved, but there was an increase in fat deposition under basal conditions and in response to a high fat diet (11). These data confirmed the importance of the ß3-adrenoceptor in OIT and suggested that, in the ß3-adrenoceptor knockout mice, alternative mechanisms for maintaining body temperature were turned on. In rodents, cold exposure was found to recruit mul- A.P. Russe 1...

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Skeletal muscle UCP2 and UCP3 expression in trained and untrained male subjects

Cited by 77 publications

References 24 publications

Slow component of V̇O2 kinetics: the effect of training status, fibre type, UCP3 mRNA and citrate synthase activity

Slow component of V̇O2 kinetics: the effect of training status, fibre type, UCP3 mRNA and citrate synthase activity

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

Old and new determinants in the regulation of energy expenditure

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