RESEARCH ARTICLE Capsiate Supplementation Reduces Oxidative Cost of Contraction in Exercising Mouse Skeletal Muscle In Vivo

Chronic administration of capsiate is known to accelerate whole-body basal energymetabolism, but the consequences in exercising skeletal muscle remain very poorly documented. In order to clarify this issue, the effect of 2-week daily administration of either vehicle (control) or purified capsiate (at 10- or 100-mg/kg body weight) on skeletal muscle function and energetics were in-vestigated throughout a multidisciplinary approach combining in vivo and in vitro measurements in mice. Mechanical performance and energy metabolismwere assessed strictly non-invasively in contracting gastrocnemiusmuscle using magnetic resonance (MR) imaging and 31-phos-phorus MR spectroscopy (31P-MRS). Regardless of the dose, capsiate treatments markedly disturbed basal bioenergetics in vivo including intracellular pH alkalosis and decreased phos-phocreatine content. Besides, capsiate administration did affect neither mitochondrial uncoupl-ing protein-3 gene expression nor both basal andmaximal oxygen consumption in isolated saponin-permeabilized fibers, but decreased by about twofold theKm of mitochondrial respira-tion for ADP. During a standardized in vivo fatiguing protocol (6-min of repeatedmaximal iso-metric contractions electrically induced at a frequency of 1.7 Hz), both capsiate treatments reduced oxidative cost of contraction by 30-40%, whereas force-generating capacity and fatiga-bility were not changed.Moreover, the rate of phosphocreatine resynthesis during the post-elec-trostimulation recovery period remained unaffected by capsiate. Both capsiate treatments further promotedmuscle mass gain, and the higher dose also reduced body weight gain and abdominal fat content. These findings demonstrate that, in addition to its anti-obesity effect, capsiate supplementation improves oxidative metabolism in exercising muscle, which strength-en this compound as a natural compound for improving health