Prolonged disturbances in citrulline metabolism following resistance exercise in COPD

Abstract

Background & aims

Disturbances in arginine (ARG) and protein metabolism, as well as in gut function have been observed in response to an endurance exercise session in patients with Chronic Obstructive Pulmonary Disease (COPD). We studied whether resistance exercise also affects the acute response in arginine (role in nitric oxide synthesis), citrulline (CIT, marker of gut health), and (muscle) protein metabolism differently in COPD as compared to healthy older adults.

Methods

Patients with stable moderate to severe COPD (n = 24) and healthy controls (n = 25) completed a high-intensity resistance exercise session in the postabsorptive state. We administered a pulse of multiple stable isotopes of amino acids before, and 1 h and 24 h post-resistance exercise to assess the whole body production (WBP) and intracellular productions by compartmental analysis of ARG and CIT, and of tau-methylhistidine (TauMETHIS), phenylalanine (PHE), tyrosine (TYR), and PHE > TYR conversion as markers of muscle (myofibrillar) protein breakdown and whole body (net) protein breakdown, respectively. Muscle fatigue was determined by assessing the decay in peak leg extension torque post-resistance exercise.

Results

COPD patients overall exhibited lower WBP ARG (p < 0.0001), CIT (p < 0.0001), PHE (p = 0.0001), TYR (p < 0.0001), and tau-METHIS (p = 0.0004) compared to controls. Resistance exercise did not change WBP of PHE, tau-METHIS, or PHE > TYR conversion, despite prolonged muscle fatigue in COPD. WBP CIT was increased at 1- and 24-h post-exercise in both groups (p < 0.003). Plasma CIT concentrations were reduced in both groups (p < 0.006) and remained lower at 24 h post-exercise in COPD only (p < 0.05) despite a third less work performed.

Conclusions

Both COPD and healthy participants exhibited upregulated whole-body citrulline production following resistance exercise. However, in COPD, this increase was insufficient to counteract the sustained reduction in plasma citrulline concentration, despite performing significantly less work during the exercise session. This prolonged disturbance in citrulline metabolism in COPD points to a potential exercise-induced enterocyte dysfunction, highlighting a novel area for understanding the impact of resistance exercise on gut health in this population.

Clinical trial registry

Trial registration ClinicalTrials.gov: NCT02780219.