O098 Diclofenac alters expression of genes regulating muscle lipid metabolism during resistance exercise training in humans, but does not change IMCL content

Abstract

Abstract Introduction Diclofenac is an NSAID commonly used off-label to reputedly enhance athletic training adaptation. Diclofenac activates PPAR-γ and upregulates the expression of lipid metabolism genes in vitro. This study investigated the impact of diclofenac administration on IMCL content and muscle genes regulating lipid metabolism during resistance exercise training in healthy volunteers. Methods Following informed consent and screening, 17 healthy, young, exercise-trained males matched for leg strength were allocated to Diclofenac (75mg diclofenac sodium daily, n=9) or Placebo (n=8) groups. Participants performed 5×30 sets of maximal isokinetic (90°/s) knee extensions with the non-dominant leg 3× weekly over 12 weeks. Vastus lateralis biopsies were obtained in the fasted state at baseline and 1, 7, 28, and 84 days of training for histochemical determination of IMCL content and muscle mRNA expression using microfluidic gene cards. IPA identified gene networks altered from baseline. Results There were significant changes in muscle mRNA expression levels associated with the upregulation of muscle lipid metabolism at all time points compared to baseline in Diclofenac. This was not evident in Placebo, where the inhibition of lipid metabolism was predicted by day 84. Mean (±SEM) IMCL content was no different between groups at baseline (7.4±3.8% Placebo vs. 6.9±2.6% Diclofenac), and no time/treatment interactions with resistance exercise training were observed (ηp2=0.07). Conclusion Diclofenac administration had a rapid, robust impact on genes regulating muscle lipid metabolism during 12 weeks of exercise training in humans. However, these responses were not associated with changes in IMCL content and further investigation is warranted.