The Effect Of Exercise Intensity On Gene Expression And Protein Function Of Rs9939609 Gene Variant In Fto

Abstract

Recent meta-analysis has shown the association between FTO risk allele and the odds of obesity to be attenuated by 27% in physically active adults, which may suggest a possible relationship between exercise and FTO protein function. PURPOSE: To examine differences in FTO gene expression and protein function following high and low intensity exercise. METHODS: Twenty eight apparently healthy untrained males and females were genotyped for the FTO rs9939609 (T>A) polymorphism, prior to performing continuous isocaloric (400 kcal) cycle ergometer exercise on two separate occasions at 80% (HI) and 40% (LO) VO2peak. Skeletal muscle biopsies were sampled from the vastus lateralis at pre exercise (0 mins), 10 and 90 mins post exercise. Differences in FTO genotype, gene and protein expression, and m6A RNA methylation status before and/or after exercise were determined using an ANOVA. RESULTS: Distribution of the FTO variant alleles was 36% homozygous (AA), 32% heterozygous (AT) and 32% wild-type alleles (TT). No significant differences between genotypes in time to expend 400 kcal during the HI (AA: 36:45 ± 2:00min:sec, AT: 39:29 ± 3:07min:sec, TT: 41:21 ± 3:02min:sec, p = 0.511) and LO intensity (AA: 54:28 ± 2:58min:sec, AT: 57:59 ± 4:06min:sec, TT: 61:04 ± 4:19min:sec, p = 0.472) exercise protocol, or for average RER, glucose utilization and fat utilization (g.kgLBM-1.T.I-1) (p<0.05) during each exercise protocol were noted. FTO mRNA expression was significantly increased at 10 mins post HI exercise (AA: 0.69-fold, AT:0.21-fold, TT: 0.23-fold, p = 0.003). No genotype or genotype by time interaction was observed (p <0.05). m6A on RNA was significantly decreased at 90 minutes following both LO and HI intensity exercise (Delta Change: HI - AA: -0.29 ± 0.10ng, AT: -0.27 ± 0.12ng, TT -0.06 ± 0.17ng, p<0.05; LO - AA: -0.07 ± 0.12ng, AT: -0.16 ± 0.11ng, TT: -0.20 ± 0.06ng, p <0.05). No genotype or genotype by time interaction was observed (p <0.05). No main effect for time, genotype or genotype by time interaction was identified for muscle FTO protein expression in response to HI and LO intensity exercise. CONCLUSIONS: Physical exercise has a significant impact of FTO gene expression and possible function. The significance of these findings requires further investigation.