AIM: In Western European populations, about 18% of all individuals have a complete deficiency of the alpha-actinin-3 protein owing to homozygosity for a stop codon mutation (R577X) in the ACTN3 gene. Actn3(-/-) knock-out mice show increased activity of multiple enzymes in the aerobic metabolic pathway in fast muscle fibres. Whether this observation is also present in human XX genotype carriers compared to RR carriers has not been studied in a fibre-type-specific approach in humans. The purpose of this study was therefore to compare fibre-type-specific oxidative enzyme activity in humans with a different ACTN3 R577X genotype. METHODS: Vastus lateralis muscle biopsy samples of 17 XX and 16 RR subjects were used to measure markers of oxidative capacity [cytochrome c oxidase (CYTOX) and succinate dehydrogenase (SDH)] in a fibre-type-specific assay using enzyme histochemistry. RESULTS: Cytochrome c oxidase staining showed no significant genotype group differences in type I or type II muscle fibres. Also, we found no significant differences in SDH staining of fast fibres comparing XX and RR carriers. CONCLUSION: In conclusion, the increase in oxidative enzyme activity of fast muscle fibres, as reported in an Actn3(-/-) knock-out mouse, was not observed in our human samples. Known differences in metabolic characteristics of muscle fibres in rodents compared to humans may in part explain this discrepancy in findings.
AIM: In Western European populations, about 18% of all individuals have a complete deficiency of the alpha-actinin-3 protein owing to homozygosity for a stop codon mutation (R577X) in the ACTN3 gene. Actn3(-/-) knock-out mice show increased activity of multiple enzymes in the aerobic metabolic pathway in fast muscle fibres. Whether this observation is also present in human XX genotype carriers compared to RR carriers has not been studied in a fibre-type-specific approach in humans. The purpose of this study was therefore to compare fibre-type-specific oxidative enzyme activity in humans with a different ACTN3R577X genotype. METHODS: Vastus lateralis muscle biopsy samples of 17 XX and 16 RR subjects were used to measure markers of oxidative capacity [cytochrome c oxidase (CYTOX) and succinate dehydrogenase (SDH)] in a fibre-type-specific assay using enzyme histochemistry. RESULTS: Cytochrome c oxidase staining showed no significant genotype group differences in type I or type II muscle fibres. Also, we found no significant differences in SDH staining of fast fibres comparing XX and RR carriers. CONCLUSION: In conclusion, the increase in oxidative enzyme activity of fast muscle fibres, as reported in an Actn3(-/-) knock-out mouse, was not observed in our human samples. Known differences in metabolic characteristics of muscle fibres in rodents compared to humans may in part explain this discrepancy in findings.
Authors: Louis Pérusse; Tuomo Rankinen; James M Hagberg; Ruth J F Loos; Stephen M Roth; Mark A Sarzynski; Bernd Wolfarth; Claude Bouchard Journal: Med Sci Sports Exerc Date: 2013-05 Impact factor: 5.411
Authors: Siacia Broos; Laurent Malisoux; Daniel Theisen; Marc Francaux; Louise Deldicque; Martine A Thomis Journal: PLoS One Date: 2012-11-08 Impact factor: 3.240
Authors: Nir Eynon; Jonatan R Ruiz; Pedro Femia; Vladimir P Pushkarev; Pawel Cieszczyk; Agnieszka Maciejewska-Karlowska; Marek Sawczuk; Dmitry A Dyatlov; Evgeny V Lekontsev; Leonid M Kulikov; Ruth Birk; David J Bishop; Alejandro Lucia Journal: PLoS One Date: 2012-08-16 Impact factor: 3.240