Skeletal muscle mitochondrial inertia is associated with carnitine acetyltransferase activity and physical function in humans

Figures

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  Figure 1. Pronounced skeletal muscle mitochondrial inertia in metabolically compromised individuals. (A) Halftime of PCr on-kinetics. (B) Linear association between PCr on-kinetics and PCr recovery after exercise. (C) Linear association between PCr on-kinetics and CrAT protein activity. (D) Linear association between PCr on-kinetics and in vivo skeletal muscle acetylcarnitine content. [s], seconds; T2DM, patients with type 2 diabetes; OB, individuals with obesity; UT, lean untrained; T, trained. Circles in blue, T2DM (n = 8); circles in red, OB (n = 8); circles in green, UT (n = 11); circles in gray, T (n = 12). Data are shown as individual points and mean ± SEM. * P < 0.05 versus untrained individuals, †P < 0.05 versus trained individuals. PCr on-kinetics could not be measured in one T2DM patient due to unreliable steady state and, therefore, are excluded for the analysis. Statistical test were 1-way ANOVA with Bonferroni post hoc correction and Pearson’s correlation.

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  Figure 2. Skeletal muscle mitochondrial inertia coexists with elevated ADP accumulation in muscle tissue during exercise. (A) ADP levels in muscle tissue increases upon exercise onset. (B) ADP levels when PCr utilization reaches a new steady state at the onset of exercise. (C) Linear association between PCr on-kinetics and ADP levels when PCr reached a new steady state during exercise. [s], seconds; T2DM, patients with type 2 diabetes; OB, individuals with obesity; UT, lean untrained; T, trained. Circles in blue, T2DM (n = 8); circles in red, OB (n = 7); circles in green, UT (n = 8); circles in gray, T (n = 12). Data are shown as individual points and mean ± SEM. †P < 0.05 versus trained volunteers. Statistical test were 1-way ANOVA with Bonferroni post hoc correction and Pearson’s correlation.

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  Figure 3. Skeletal muscle mitochondrial inertia and reduced functional outcomes in older sedentary individuals. (A) Halftime of PCr on-kinetics. (B) Halftime of PCr recovery after exercise. (C) Linear association between PCr on-kinetics and PCr recovery after exercise. (D) Walking speed upon performing the 6-minute walking test (6MWT). (E) Seating and standing upon performing the chair-stand test. (F) Gross exercise efficiency. (G) Net exercise efficiency upon performing a submaximal cycling test. [s], seconds; Y, young; OT, older trained; O, older with normal physical activity. Circles in black, Y (n = 10); circles in red, OT (n = 17); circles in blue, O (n = 15). Data are shown as individual points and mean ± SD. ‡P < 0.05 versus Y individuals, *P < 0.05 versus OT individuals. One participant from Y and 2 participants from OT did not perform the 6MWT due to scheduling issues. Two other participants from OT did not perform the chair-stand test due to scheduling issues. Statistical test were 1-way ANOVA with Bonferroni post hoc correction and Pearson’s correlation.

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  Figure 4. Skeletal muscle mitochondrial inertia is associated with physical function and exercise efficiency in humans. (A–D) Linear association between PCr on-kinetics and walking speed (A), chair seating-standing exercise performance (B), gross (C), and net exercise efficiency (D). [s], seconds; Y, young; OT, older trained; O, older with normal physical activity. Circles in black, Y (n = 10); circles in red, OT (n = 17); circles in blue, O (n = 15). Statistical test was Pearson’s correlation.