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Muscle uncoupling protein 3 overexpression mimics endurance training and reduces circulating biomarkers of incomplete ?-oxidation.

ABSTRACT: Exercise substantially improves metabolic health, making the elicited mechanisms important targets for novel therapeutic strategies. Uncoupling protein 3 (UCP3) is a mitochondrial inner membrane protein highly selectively expressed in skeletal muscle. Here we report that moderate UCP3 overexpression (roughly 3-fold) in muscles of UCP3 transgenic (UCP3 Tg) mice acts as an exercise mimetic in many ways. UCP3 overexpression increased spontaneous activity (?40%) and energy expenditure (?5-10%) and decreased oxidative stress (?15-20%), similar to exercise training in wild-type (WT) mice. The increase in complete fatty acid oxidation (FAO; ?30% for WT and ?70% for UCP3 Tg) and energy expenditure (?8% for WT and 15% for UCP3 Tg) in response to endurance training was higher in UCP3 Tg than in WT mice, showing an additive effect of UCP3 and endurance training on these two parameters. Moreover, increases in circulating short-chain acylcarnitines in response to acute exercise in untrained WT mice were absent with training or in UCP3 Tg mice. UCP3 overexpression had the same effect as training in decreasing long-chain acylcarnitines. Outcomes coincided with a reduction in muscle carnitine acetyltransferase activity that catalyzes the formation of acylcarnitines. Overall, results are consistent with the conclusions that circulating acylcarnitines could be used as a marker of incomplete muscle FAO and that UCP3 is a potential target for the treatment of prevalent metabolic diseases in which muscle FAO is affected.

SUBMITTER: Aguer C

PROVIDER: S-EPMC4046190 | biostudies-other | 2013 Oct

REPOSITORIES: biostudies-other

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Muscle uncoupling protein 3 overexpression mimics endurance training and reduces circulating biomarkers of incomplete β-oxidation.

Aguer Céline C Fiehn Oliver O Seifert Erin L EL Bézaire Véronic V Meissen John K JK Daniels Amanda A Scott Kyle K Renaud Jean-Marc JM Padilla Marta M Bickel David R DR Dysart Michael M Adams Sean H SH Harper Mary-Ellen ME

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20130628 10

Exercise substantially improves metabolic health, making the elicited mechanisms important targets for novel therapeutic strategies. Uncoupling protein 3 (UCP3) is a mitochondrial inner membrane protein highly selectively expressed in skeletal muscle. Here we report that moderate UCP3 overexpression (roughly 3-fold) in muscles of UCP3 transgenic (UCP3 Tg) mice acts as an exercise mimetic in many ways. UCP3 overexpression increased spontaneous activity (∼40%) and energy expenditure (∼5-10%) and d ...[more]

PMID: 23825224

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Project description:BackgroundDespite the positive effects of endurance training on the cardiovascular (CV) system, excessive exercise induces not only physiological adaptations but also adverse changes in CV system, including the heart. We aimed to evaluate the selected miRNAs expression based on bioinformatic analysis and their changes before and after an ultramarathon run.Materials and methodsCardiac tissue-specific targets were identified with the Tissue 2.0 database. Gene-gene interaction data were retrieved from the STRING app for Cytoscape. Twenty-three endurance athletes were recruited to the study. Athletes ran to completion (100 km) or exhaustion (52-91 km, median 74 km). All participants completed pre- and post-run testing. miRNAs expressions were measured both before and after the race.ResultsEnrichment analysis of the signaling pathways associated with the genes targeted by miRNAs selected for qRT-PCR validation (miR-1-3p, miR-126, miR-223, miR-125a-5p, miR-106a-5p, and miR-15a/b). All selected miRNAs showed overlap in regulation in pathways associated with cancer, IL-2 signaling, TGF-β signaling as well as BDNF signaling pathway. Analysis of metabolites revealed significant regulation of magnesium and guanosine triphosphate across analyzed miRNA targets. MiR-1-3p, miR-125a-5p, miR-126, and miR-223 expressions were measured in 23 experienced endurance athletes, before and after an ultramarathon wherein athletes ran to completion (100 km) or exhaustion (52-91 km, median 74 km). The expressions of miR-125a-5p, miR-126, and miR-223 were significantly increased after the race (p = 0.007, p = 0.001, p = 0.014, respectively). MiR-1-3p expression post-run showed a negative correlation with the post-run levels of high-sensitivity C-reactive protein (hs-CRP) (r = -0.632, p = 0.003). Higher miR-1-3p expression was found in runners, who finished the race under 10 h compared to runners who finished over 10 h (p = 0.001). Post-run miR-125a-5p expression showed a negative correlation with the peak lactate during the run (r = -0.576, p = 0.019).ConclusionExtreme physical activity, as exemplified by an ultramarathon, is associated with changes in circulating miRNAs' expression related to inflammation, fibrosis, and cardiac muscle function. In particular, the negative correlations between miR-125a-5p and lactate concentrations, and miR-1-3p and hs-CRP, support their role in specific exercise-induced adaptation. Further studies are essential to validate the long-term effect of these observations.

Project description:Hamstring strains are the most common injury in multiple sprint sports, with inadequate eccentric hamstring strength and fatigue identified as important risk factors. Resistance training interventions aimed at reducing injury risk typically focus on the development of maximum strength, while little is known about the impact of training on hamstring fatigue resistance. The present study compared the effects of strength endurance (SE) with a strength intervention (S) on the eccentric hamstring strength decline induced by a simulated soccer match. Twenty-one female soccer players were randomly assigned to a S group (n = 10) or a SE group (n = 11). Hamstrings and quadriceps isokinetic concentric and eccentric peak torque (PT) were assessed at 120°.s-1 and hamstrings-to-quadriceps ratio (HEcc:QCon) calculated, pre- and immediately post a 90-min simulated match (BEAST90). This was repeated following a 7-week intervention of either three to five sets of 6RM leg curl and stiff-leg deadlift with 3-min inter-set rest (S), or the same exercises performed using three sets of 12-20 RM with 45-90 s inter-set rest (SE). At baseline, the simulated match led to significant declines in hamstrings eccentric peak torque (EccPT) in both groups in both dominant (D) and non-dominant (ND) legs [SE: (D: -15.5, ND: -15.6%), P = 0.001 to 0.016; S: (D: -12.3%, ND: -15.5%), P = 0.001 to 0.018]. After the 7-week intervention, we observed a group?intervention?match interaction such that there was no significant decline in EccPT in the SE group following the simulated match (D: 5.3%, ND: 2.0%), but there remained significant declines in the S group (D: -14.2%, ND: -15.5%, P = 0.018-0.001). Similarly, in the SE group, there was a significant decrease in the HEcc:QCon in D before (-14.2%, P = 0.007), but not after the training intervention, whereas declines were observed in the S group both at baseline, and following the intervention (D: -13.9%, ND: -15.6%, P = 0.045). These results demonstrate that SE training can reduce the magnitude of the EccPT decline observed during soccer competition. As inadequate eccentric strength and fatigue are both risk factors for hamstring injury, SE training should be considered along with the development of peak eccentric strength, as a component of programs aimed at reducing injury risk in multiple-sprint sports.

Dataset Information

Muscle uncoupling protein 3 overexpression mimics endurance training and reduces circulating biomarkers of incomplete ?-oxidation.

Publications

Muscle uncoupling protein 3 overexpression mimics endurance training and reduces circulating biomarkers of incomplete β-oxidation.

Similar Datasets

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