Effects Of A Botanical Supplement On Gene Expression Of Peroxisome Proliferator-Activated Receptor Proteins Following Eccentric Exercise

Abstract

Inflammation and oxidative stress contribute to eccentric exercise-induced muscle damage. Research shows that antioxidant supplements may attenuate this damage, but the molecular mechanisms underlying the effect are not well known. PURPOSE: This study examined the effect of a botanical supplement containing mixtures of plant extracts with anti-inflammatory and antioxidant properties on changes in gene expression following eccentric exercise. METHODS: 19 healthy men (18-30 yrs) were randomly assigned to receive the placebo or supplement for 35d. Stage 1 - subjects exercised one leg (knee extensors) and a muscle biopsy (vastus lateralis) was taken at 3hrs post-exercise; Stage 2 - subjects took a dietary supplement or placebo for 28d; Stage 3 - subjects repeated the exercise with the contralateral leg and a muscle biopsy was taken at 3hrs post-exercise. Expression profiling was performed using Agilent Whole Genome arrays. Differentially expressed genes for the supplement vs. placebo groups were imported into Ingenuity Pathway Analysis software (IPA) for network analysis. Selected genes identified by IPA were further analyzed by quantitative real-time (qRT)-PCR. Other parameters assessed were muscle soreness, strength loss, and serum creatine kinase (CK) activity. RESULTS: Compared with the placebo group (N=9), 588 genes were differentially expressed (p<0.02) in the supplement group after supplementation (N=10). Among the genes modified, peroxisome proliferator-activated receptor alpha (PPARA), peroxisome proliferator-activated receptor delta (PPARD), 3-phosphoinositide dependent protein kinase-1 (PDPK1), and acyl-CoA oxidase 1 (ACOX1) were identified by IPA as key network elements; these genes are components of the known PPAR pathways. qRT-PCR was performed on these genes, but only PPARD was up-regulated in the supplement vs. placebo group (p<0.05). There was no effect of the supplement on soreness or serum CK, but strength loss post-supplementation was reduced in the supplement group (p<0.05). CONCLUSION: Although PPARD has been previously studied regarding obesity, it may also play a role in reducing negative consequences of eccentric exercise through PPARD pathways yet to be identified. Supported by Interleukin Genetics, Inc, Waltham, MA and Nutrilite Health Institute, Buena Park, CA.