FASEB J. 2026 May 15;40(9):e71813. doi: 10.1096/fj.202600123RR.
ABSTRACT
The common ACTN3 R577X polymorphism leads to α-actinin-3 deficiency in ~20% of the human population and may be detrimental to their muscle power. However, the impact of ACTN3R577X on metabolic health and exercise capacity in the general population remains unclear. The objective of the current study was to compare metabolic health markers, musculoskeletal traits, and cardiorespiratory capacity between untrained overweight α-actinin-3-deficient (XX; 20 men and 19 women) and α-actinin-3 expressing (RR; 20 men and 21 women) individuals. The participants were aged 43 ± 7 years and had a BMI of 28.6 ± 3.2 kg·m-2. Various metabolic health and exercise capacity aspects encompassing segmental body composition, bone density, systemic low-grade inflammation, blood lipid profile, whole-body glucose tolerance and insulin sensitivity, resting and exercise metabolism, and exercise capacity were evaluated. While XX groups had lower fat-free mass than RR groups, other anthropometrical and body composition features, including bone mineral content, did not differ between the genotype groups in either women or men. We found no significant differences between XX and RR individuals for blood lipid profile, markers of systemic inflammation, glucose tolerance, resting metabolism, and leg strength. Moreover, no clear genotype-related differences were observed in markers of insulin resistance and sensitivity, although XX women exhibited a slightly smaller increase in insulin concentration than RR women during an oral glucose tolerance test. An incremental cardiopulmonary cycling test revealed no differences in metabolic and heart rate responses, maximal fat oxidation, or exercise capacity. In conclusion, we observed no associations between α-actinin-3 deficiency and metabolic health, body composition, muscle function, or cardiorespiratory capacity in untrained overweight men and women.
PMID:42033161 | DOI:10.1096/fj.202600123RR