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In addition to its role in substrate selection (carbohydrate vs. fat) for oxidative metabolism in muscle, acetylcarnitine production may be an important modulator of the energetic pathway by which ATP is produced. A combination of noninvasive magnetic resonance spectroscopy measures of cytosolic acetylcarnitine and ATP production pathways was used to investigate the link between [acetylcarnitine] and energy production in vivo. Intracellular metabolites were measured in the vastus lateralis muscle of eight males (mean: 28.4 yr, range: 25-35) during 8 min of incremental, dynamic contractions (0.5 Hz, 2-min stages at 6%, 9%, 12%, and 15% maximal torque) that increased [acetylcarnitine] approximately fivefold from resting levels. ATP production via oxidative phosphorylation, glycolysis, and the creatine kinase reaction was calculated based on phosphorus metabolites and pH. Spearman rank correlations indicated that postcontraction [acetylcarnitine] was positively associated with both absolute (mM) and relative (% total ATP) glycolytic ATP production (rs = 0.95, P = 0.001; rs = 0.93, P = 0.002), and negatively associated with relative (ss = 0.81, P = 0.02) but not absolute (rs = 0.14, P = 0.75) oxidative ATP production. Thus, acetylcarnitine accumulated more when there was a greater reliance on "nonoxidative" glycolysis and a relatively lower contribution from oxidative phosphorylation, reflecting the fate of pyruvate in working skeletal muscle. Furthermore, these data indicate striking interindividual variation in responses to the energy demand of submaximal contractions. Overall, the results of this preliminary study provide novel evidence of the coupling in vivo between ATP production pathways and the carnitine system. NEW & NOTEWORTHY Production of acetylcarnitine from acetyl-CoA and free carnitine may be important for energy pathway regulation in contracting skeletal muscle. Noninvasive magnetic resonance spectroscopy was used to investigate the link between acetylcarnitine and energy production in the vastus lateralis muscle during dynamic contractions (n = 8 individuals). A positive correlation between acetylcarnitine accumulation and "nonoxidative" glycolysis and an inverse relationship with oxidative phosphorylation, provides novel evidence of the coupling between ATP production and the carnitine system in vivo. [ABSTRACT FROM AUTHOR]

The cause and consequences of inosine monophosphate (IMP) formation when adenosine triphosphate (ATP) declines during muscular contractions in vivo are not fully understood. The purpose of this study was to examine the role of IMP formation in the maintenance of the Gibbs free energy for ATP hydrolysis (ΔG ATP ) during dynamic contractions of increasing workload and the implications of ATP loss in vivo. Eight males (median 27.5, 25-35 yr range) completed an 8-min incremental protocol [2-min stages of isotonic knee extensions (0.5 Hz)] in a 3-T magnetic resonance (MR) system. Phosphorus MR spectra were obtained from the knee extensor muscles at rest and during contractions and recovery. Although the ATP demand during contractions was met primarily by oxidative phosphorylation, [ATP] decreased from 8.2 mM to 7.5 (range 6.4-8.0) mM and [IMP] increased from 0 mM to 0.6 (0.1-1.7) mM. Modeling showed that, in the absence of IMP formation, excess adenosine diphosphate (ADP) would result in a less favorable ΔG ATP ( P < 0.001). Neither [ATP] nor [IMP] had returned to baseline following 10 min of recovery ( P < 0.001). Notably, Δ[ATP] was linearly related to the post-contraction reduction in muscle oxidative capacity ( r = 0.74, P = 0.037). Our results highlight the importance of IMP formation in preserving cellular energy status by avoiding increases in ADP above that necessary to stimulate energy production pathways. However, the consequence of IMP formation was an incomplete recovery of [ATP], which in turn was related to decreased muscle oxidative capacity following contractions. These results likely have implications for the capacity to generate adequate energy during repeated bouts of muscular work. NEW & NOTEWORTHY An ∼9% decline in [ATP] led to the formation of inosine monophosphate (IMP) during submaximal muscular contractions. Modeling revealed IMP formed to preserve a favorable energy state (ΔG ATP ) by minimizing large increases in [ADP], whereas the loss of [ATP] did not alter ΔG ATP . [ATP] did not recover by 10 min, and the loss of [ATP] was associated with a reduced oxidative capacity, providing a new link between [ATP] loss and an impaired energetic capacity in vivo.

Exercise interventions in chronic kidney disease (CKD) have received growing interest, with over 30 meta-analyses published in the past 5 years. The potential benefits of exercise training in CKD range from slowing disease progression to improving comorbidities and quality of life. Nevertheless, there is a lack of large, randomized control trials in diverse populations, particularly regarding exercise in nondialysis-dependent CKD (NDD). When exercise interventions are implemented, they often lack fundamental features of exercise training such as progressive overload, personalization, and specificity. Furthermore, the physiology of exercise and CKD-specific barriers appear poorly understood. This review explores the potential benefits of exercise training in NDD, draws lessons from previous interventions and other fields, and provides several basic tools that may help improve interventions in research and practice., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)