A single bout of cycling exercise induces nucleosome repositioning in the skeletal muscle of lean and overweight/obese individuals

Abstract

Aim: To compare the molecular and metabolic effects of a single exercise bout in the skeletal muscle between lean and overweight/obese (Ov/Ob) individuals.Materials and Methods: Participants recruited were men, aged 19-30 years, who were either lean (body mass index [BMI] < 25, 18.5À24.1 kg/m 2 ; n = 15) or Ov/Ob (BMI ≥ 25, 25.5À36.9 kg/m 2 ; n = 15). Four hours after a high-carbohydrate breakfast (7 kcal/kg; 60% carbohydrate, 25% fat, 15% protein), participants performed a cycling exercise (50% VO 2 max, expending ~650 kcal). Muscle biopsies and peripheral blood samples were collected 30 minutes before the meal and immediately after exercise. Blood analysis, and muscle acylcarnitine profiles, transcriptomics, and nucleosome mapping by micrococcal nuclease digestion with deep sequencing were performed.Results: A single exercise bout improved blood metabolite profiles in both lean and Ov/Ob individuals. Muscle long-chain acylcarnitines were increased in Ov/Ob compared with lean participants, but were not altered by exercise. A single exercise bout increased the mRNA abundance of genes related to mitochondria and insulin signalling in both lean and Ov/Ob participants. Nucleosome mapping by micrococcal nuclease digestion with deep sequencing revealed that exercise repositioned the -1 nucleosome away from the transcription start site of the PGC1a promoter and of other mitochondrial genes, but did not affect genes related to insulin signalling, in both lean and Ov/Ob participants. Conclusion:These data suggest that a single exercise bout induced epigenetic alterations in skeletal muscle in a BMI-independent manner.

Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity

“…We also compared the SLU-PP-332-induced DEGs from both muscle types to DEGs from the quadricep muscle identified in human acute aerobic exercise (single bout of cycling�650 kcal@50% VO 2 max). 54 As shown in Figure 3G, there was a significant overlap between both the SLU-PP-332 quadricep (p < 2.3 × 10 −14 ) and gastrocnemius muscle DEGs (p < 3.7 × 10 −15 ) and the DEGs from the quadriceps muscle of lean human patients subjected to acute exercise (FDR < 0.05, |FC| > 1.5). Sixteen genes were shared among the three groups and include both Ddit4 and Slc25a25 (Figure 3G).…”

“…Seventeen genes were shared among the three groups and include 4 of the top 10 upregulated genes identified by Gordon et al in the DDIT4/REDD1 acute aerobic exercise pathway ( Ddit4 , Mt2 , Slc25a25 , and Sik1 ). We also compared the SLU-PP-332-induced DEGs from both muscle types to DEGs from the quadricep muscle identified in human acute aerobic exercise (single bout of cycling650 kcal@50% VO 2 max) . As shown in Figure G, there was a significant overlap between both the SLU-PP-332 quadricep ( p < 2.3 × 10 –14 ) and gastrocnemius muscle DEGs ( p < 3.7 × 10 –15 ) and the DEGs from the quadriceps muscle of lean human patients subjected to acute exercise (FDR < 0.05, |FC| > 1.5).…”

Exercise Is Medicine: How Do We Implement It?

“…Exercise not only improves outcomes in obesity, T2D, CVD, etc., but also alters the epigenome. Exercise impacts HDAC activity [ 59 ], histone acetylation [ 60 ], histone methylation [ 61 ], histone phosphorylation [ 62 ], DNA methylation [ 63 , 64 ], nucleosome positioning [ 64 , 65 ], and, it has been postulated, lactylation [ 66 ]. Furthermore, exercise-induced epigenetic alterations have been shown to be inherited by offspring [ 67 ].…”

“…Additionally, the effects of maternal exercise may abolish any detrimental metabolic effects of obesity on offspring via epigenetic mechanisms [ 44 ]. While it is clear that exercise training affects epigenetic modifications and these modifications are heritable and improve obesity- and T2DM-related outcomes [ 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ], studies on the potential heritable effects of exercise on CVD, stroke, cancer, etc., are lacking. However, given the pleotropic effects of exercise in preventing and improving T2D and obesity and its ability to alter the epigenome [ 10 , 12 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ], it is possible that the effects of maternal and paternal exercise are far-reaching and affect offspring outcomes with respect to other chronic disease states.…”