Metabolite patterns of patients with peripheral arterial disease in response to exercise

Supervised exercise therapy (SET) is an effective intervention for symptomatic peripheral artery disease. Its effect on metabolism, measured by the circulating metabolome is not well understood. Participants underwent the Gardner graded treadmill test before and after SET and blood was sampled before and after each treadmill test. We tested the average association of metabolite levels with timing of blood draws. We used five models to identify metabolites or changes in metabolites at specific time points that associate with treadmill test performance or inter-individual variability in functional performance after SET. When analyzing individual time points, high levels of anandamide (AEA) before any exercise interventions were associated with shorter, or worse, walking time. Increased arachidonic acid (AA) and decreased levels of AA precursors (dihomo-{gamma}-linolenic acid and diacylglycerol) before any exercise was associated with shorter walking times. Participants who tolerated large increases in AA during acute exercise had longer, or better, walking times before and after SET. We identified two pathways of relevance to individual response to SET: AEA synthesis may increase the activity at endocannabinoid receptors, resulting in worse treadmill test performance. SET may help train patients withstand higher levels of AA and inflammatory signaling, resulting in longer walking times.