| 1. |
- Barres, R., et al.
(författare)
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Acute exercise remodels promoter methylation in human skeletal muscle
- 2012
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 15:3, s. 405-11
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation is a covalent biochemical modification controlling chromatin structure and gene expression. Exercise elicits gene expression changes that trigger structural and metabolic adaptations in skeletal muscle. We determined whether DNA methylation plays a role in exercise-induced gene expression. Whole genome methylation was decreased in skeletal muscle biopsies obtained from healthy sedentary men and women after acute exercise. Exercise induced a dose-dependent expression of PGC-1alpha, PDK4, and PPAR-delta, together with a marked hypomethylation on each respective promoter. Similarly, promoter methylation of PGC-1alpha, PDK4, and PPAR-delta was markedly decreased in mouse soleus muscles 45 min after ex vivo contraction. In L6 myotubes, caffeine exposure induced gene hypomethylation in parallel with an increase in the respective mRNA content. Collectively, our results provide evidence that acute gene activation is associated with a dynamic change in DNA methylation in skeletal muscle and suggest that DNA hypomethylation is an early event in contraction-induced gene activation.
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| 2. |
- Barres, R., et al.
(författare)
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Non-CpG methylation of the PGC-1alpha promoter through DNMT3B controls mitochondrial density
- 2009
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 10:3, s. 189-98
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic modification through DNA methylation is implicated in metabolic disease. Using whole-genome promoter methylation analysis of skeletal muscle from normal glucose-tolerant and type 2 diabetic subjects, we identified cytosine hypermethylation of peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1 alpha (PGC-1alpha) in diabetic subjects. Methylation levels were negatively correlated with PGC-1alpha mRNA and mitochondrial DNA (mtDNA). Bisulfite sequencing revealed that the highest proportion of cytosine methylation within PGC-1alpha was found within non-CpG nucleotides. Non-CpG methylation was acutely increased in human myotubes by exposure to tumor necrosis factor-alpha (TNF-alpha) or free fatty acids, but not insulin or glucose. Selective silencing of the DNA methyltransferase 3B (DNMT3B), but not DNMT1 or DNMT3A, prevented palmitate-induced non-CpG methylation of PGC-1alpha and decreased mtDNA and PGC-1alpha mRNA. We provide evidence for PGC-1alpha hypermethylation, concomitant with reduced mitochondrial content in type 2 diabetic patients, and link DNMT3B to the acute fatty-acid-induced non-CpG methylation of PGC-1alpha promoter.
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| 3. |
- Czepluch, F. S., et al.
(författare)
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Strenuous physical exercise adversely affects monocyte chemotaxis
- 2011
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 105:1, s. 122-30
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Tidskriftsartikel (refereegranskat)abstract
- Physical exercise is important for proper cardiovascular function and disease prevention, but it may influence the immune system. We evaluated the effect of strenuous exercise on monocyte chemotaxis. Monocytes were isolated from blood of 13 young, healthy, sedentary individuals participating in a three-week training program which consisted of repeated exercise bouts. Monocyte chemotaxis and serological biomarkers were investigated at baseline, after three weeks training and after four weeks recovery. Chemotaxis towards vascular endothelial growth factor-A (VEGF-A) and transforming growth factor-beta1 (TGF-beta1) was completely inhibited immediately after training (p<0.01), and remained so after four weeks recovery. Likewise, monocyte chemoattractant protein-1 (MCP-1)-induced migration declined after training (p<0.01) and improved only partially during the recovery period. MCP-1 serum levels were significantly reduced after four weeks recovery compared to baseline (p<0.01). Total blood antioxidant capacity was enhanced at this time point (p<0.01). Monocyte chemokinesis, TGF-beta1 and nitric oxide serum levels remained unchanged during the study. Strenuous three-week training consisting of repeated exercise bouts in healthy, sedentary individuals reduces monocyte chemotaxis. It remains to be established, whether this is a sound adaptation to increased stimuli or an untoward reaction to overtraining. Nevertheless, the effect remains for several weeks with no exercise.
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| 4. |
- Fritz, T., et al.
(författare)
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Effects of Nordic walking on health-related quality of life in overweight individuals with type 2 diabetes mellitus, impaired or normal glucose tolerance
- 2011
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071. ; 28:11, s. 1362-1372
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To assess the effects of 4 months of increased physical activity on health-related quality of life in overweight individuals with Type 2 diabetes mellitus, normal or impaired glucose tolerance. METHODS: We included 212 individuals without severe physical or cardiovascular impairments aged 61 (57-64) years, with BMI of 29 (27.5-32) kg/m(2). Numbers are median (25th-75th percentile). Subjects were stratified based on normal glucose tolerance (n = 128), impaired glucose tolerance (n = 34) or Type 2 diabetes mellitus (n = 50). They were randomized into either a control group (n= 125), who maintained unaltered habitual lifestyle, or an exercise intervention group (n = 87), who were directed to engage in Nordic walking with walking poles, 5 h per week over 4 months. Self-reported physical activity and health-related quality of life was assessed at the time of inclusion and after 4 months. RESULTS: Baseline health-related quality of life of this study cohort was similar to, or better than, an age- and sex-matched Swedish population sample, for 12 of 13 scales. Quality of sleep and BMI were improved for participants with normal glucose tolerance after 4 months of Nordic walking, with little or no musculoskeletal pain as compared with control subjects. No correlation was evident between improved quality of sleep and improved BMI. CONCLUSIONS: Quality of sleep improved in the group with normal glucose tolerance following 4 months of Nordic walking. BMI reduction did not account for this improvement. Nordic walking can be introduced in a primary health care setting as a low-cost mode of exercise that promotes weight loss and improved health satisfaction.
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| 5. |
- Glund, S., et al.
(författare)
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Interleukin-6 directly increases glucose metabolism in resting human skeletal muscle
- 2007
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 56:6, s. 1630-7
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin (IL)-6 is a proinflammatory cytokine shown to modify insulin sensitivity. Elevated plasma levels of IL-6 are observed in insulin-resistant states. Interestingly, plasma IL-6 levels also increase during exercise, with skeletal muscle being the predominant source. Thus, IL-6 has also been suggested to promote insulin-mediated glucose utilization. In this study, we determined the direct effects of IL-6 on glucose transport and signal transduction in human skeletal muscle. Skeletal muscle strips were prepared from vastus lateralis biopsies obtained from 22 healthy men. Muscle strips were incubated with or without IL-6 (120 ng/ml). We found that IL-6 increased glucose transport in human skeletal muscle 1.3-fold (P < 0.05). A 30-min pre-exposure to IL-6 did not affect insulin-stimulated glucose transport. IL-6 also increased skeletal muscle glucose incorporation into glycogen, as well as glucose oxidation (1.5- and 1.3-fold, respectively; P < 0.05). IL-6 increased phosphorylation of STAT3 (signal transducer and activator of transcription 3; P < 0.05), AMP-activated protein kinase (P = 0.063), and p38 mitogen-activated protein kinase (P < 0.05) and reduced phosphorylation of S6 ribosomal protein (P < 0.05). In contrast, phosphorylation of protein kinase B/Akt, AS160 (Akt substrate of 160 kDa), and GSK3alpha/beta (glycogen synthase kinase 3alpha/beta) as well as insulin receptor substrate 1-associated phosphatidylinositol 3-kinase activity remained unaltered. In conclusion, acute IL-6 exposure increases glucose metabolism in resting human skeletal muscle. Insulin-stimulated glucose transport and insulin signaling were unchanged after IL-6 exposure.
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| 6. |
- Ring, M., et al.
(författare)
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Influence of physical activity and gender on arterial function in type 2 diabetes, normal and impaired glucose tolerance
- 2015
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Ingår i: Diabetes & Vascular Disease Research. - : SAGE Publications. - 1479-1641 .- 1752-8984. ; 12:5, s. 315-324
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Tidskriftsartikel (refereegranskat)abstract
- To determine whether Nordic walking improves cardiovascular function in middle-aged women and men, we included 121 with normal glucose tolerance, 33 with impaired glucose tolerance and 47 with Type 2 diabetes mellitus in a randomized controlled study. The intervention group added Nordic walking 5h/week for 4months to their ordinary activities. Aortic pulse wave velocity, aortic augmentation index, stiffness index, reflection index, intima-media thickness in the radial and carotid arteries, echogenicity of the carotid intima-media and systemic vascular resistance were measured. While baseline blood pressure did not differ by gender or diagnosis, aortic augmentation index was found to be higher in women in all groups. Vascular function was unchanged with intervention, without differences by gender or diagnosis. In conclusion, 4months of Nordic walking is an insufficient stimulus to improve vascular function. Future studies should consider hard endpoints in addition to measures of vascular health, as well as larger population groups, long-term follow-up and documented compliance to exercise training.
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