Insulin sensitivity, body composition and adipose depots following 12 w combined endurance and strength training in dysglycemic and normoglycemic sedentary men

Langleite, Torgrim M.; Jensen, Jørgen; Norheim, Frode; Gulseth, Hanne Løvdal; Tangen, Daniel S.; Kolnes, Kristoffer Jensen; Heck, Ansgar; Storås, Tryggve H.; Grøthe, Guro; Dahl, Marius Adler; Kielland, Anders; Holen, Torgeir; Noreng, Hans Jørgen; Stadheim, Hans Kristian; Bjørnerud, Atle; Johansen, Egil Ivar; Nellemann, Birgitte; Birkeland, Kåre I.; Drevon, Christian A.

doi:10.1080/13813455.2016.1202985

Cited by 62 publications

(123 citation statements)

References 64 publications

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“…A human exercise intervention trial (NCT01803568) was performed as described before [21]. The National Committee for Research Ethics North (Tromsø, Oslo, Norway) approved the trial.…”

Section: Methodsmentioning

confidence: 99%

“…The participants underwent 12 weeks of supervised exercise training with two interval sessions (bicycle) and two whole-body strength-training sessions per week [21]. Bicycle tests (45 min at 70% of VO 2 max) were conducted before and after the long-term training intervention [21].…”

Section: Methodsmentioning

confidence: 99%

“…Bicycle tests (45 min at 70% of VO 2 max) were conducted before and after the long-term training intervention [21]. Blood samples and biopsies from m. vastus lateralis were collected before, immediately after, and 2 h after the acute bicycle tests (Figure 1A).…”

Section: Methodsmentioning

confidence: 99%

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Global mRNA sequencing of human skeletal muscle: Search for novel exercise-regulated myokines

Pourteymour

Eckardt

Holen

et al. 2017

Molecular Metabolism

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ObjectiveSkeletal muscle is an important secretory organ, producing and releasing numerous myokines, which may be involved in mediating beneficial health effects of physical activity. More than 100 myokines have been identified by different proteomics approaches, but these techniques may not detect all myokines. We used mRNA sequencing as an untargeted approach to study gene expression of secreted proteins in skeletal muscle upon acute as well as long-term exercise.MethodsTwenty-six middle-aged, sedentary men underwent combined endurance and strength training for 12 weeks. Skeletal muscle biopsies from m. vastus lateralis and blood samples were taken before and after an acute bicycle test, performed at baseline as well as after 12 weeks of training intervention. We identified transcripts encoding secretory proteins that were changed more than 1.5-fold in muscle after exercise. Secretory proteins were defined based on either curated UniProt annotations or predictions made by multiple bioinformatics methods.ResultsThis approach led to the identification of 161 candidate secretory transcripts that were up-regulated after acute exercise and 99 that where increased after 12 weeks exercise training. Furthermore, 92 secretory transcripts were decreased after acute and/or long-term physical activity. From these responsive transcripts, we selected 17 candidate myokines sensitive to short- and/or long-term exercise that have not been described as myokines before. The expression of these transcripts was confirmed in primary human skeletal muscle cells during in vitro differentiation and electrical pulse stimulation (EPS). One of the candidates we identified was macrophage colony-stimulating factor-1 (CSF1), which influences macrophage homeostasis. CSF1 mRNA increased in skeletal muscle after acute and long-term exercise, which was accompanied by a rise in circulating CSF1 protein. In cultured muscle cells, EPS promoted a significant increase in the expression and secretion of CSF1.ConclusionWe identified 17 new, exercise-responsive transcripts encoding secretory proteins. We further identified CSF1 as a novel myokine, which is secreted from cultured muscle cells and up-regulated in muscle and plasma after acute exercise.

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“…A human exercise intervention trial (NCT01803568) was performed as described before [21]. The National Committee for Research Ethics North (Tromsø, Oslo, Norway) approved the trial.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Global mRNA sequencing of human skeletal muscle: Search for novel exercise-regulated myokines

Pourteymour

Eckardt

Holen

et al. 2017

Molecular Metabolism

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“…The research performed in this study was approved, as part of a larger project: Skeletal Muscles, Myokines and Glucose Metabolism (MyoGlu) [26]. The study adhered to the Declaration of Helsinki, and it was registered with the US National Library of Medicine Clinical Trials registry (NCT01803568).…”

Section: Methodsmentioning

confidence: 99%

“…The biopsies were taken 2 hours after an acute exercise test [26]. To take part in the study the participants had to be sedentary men (not regularly exercising more than once a week), 40 to 62 years old, non-smokers and of Nordic ethnicity.…”

Section: Methodsmentioning

confidence: 99%

Exercise in vivo marks human myotubes in vitro: Training-induced increase in lipid metabolism

et al. 2017

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Background and aimsPhysical activity has preventive as well as therapeutic benefits for overweight subjects. In this study we aimed to examine effects of in vivo exercise on in vitro metabolic adaptations by studying energy metabolism in cultured myotubes isolated from biopsies taken before and after 12 weeks of extensive endurance and strength training, from healthy sedentary normal weight and overweight men.MethodsHealthy sedentary men, aged 40–62 years, with normal weight (body mass index (BMI) < 25 kg/m2) or overweight (BMI ≥ 25 kg/m2) were included. Fatty acid and glucose metabolism were studied in myotubes using [14C]oleic acid and [14C]glucose, respectively. Gene and protein expressions, as well as DNA methylation were measured for selected genes.ResultsThe 12-week training intervention improved endurance, strength and insulin sensitivity in vivo, and reduced the participants’ body weight. Biopsy-derived cultured human myotubes after exercise showed increased total cellular oleic acid uptake (30%), oxidation (46%) and lipid accumulation (34%), as well as increased fractional glucose oxidation (14%) compared to cultures established prior to exercise. Most of these exercise-induced increases were significant in the overweight group, whereas the normal weight group showed no change in oleic acid or glucose metabolism.Conclusions12 weeks of combined endurance and strength training promoted increased lipid and glucose metabolism in biopsy-derived cultured human myotubes, showing that training in vivo are able to induce changes in human myotubes that are discernible in vitro.

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Effects of long-term exercise on plasma adipokine levels and inflammation-related gene expression in subcutaneous adipose tissue in sedentary dysglycaemic, overweight men and sedentary normoglycaemic men of healthy weight

et al. 2019

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Aims/hypothesis Obesity and insulin resistance may be associated with altered expression and secretion of adipokines. Physical activity can markedly improve insulin sensitivity, but the association with adipokines remains largely unknown. In this study, we examined the effects of physical activity on the subcutaneous white adipose tissue (scWAT) secretome and its relationship to insulin sensitivity. Methods As reported previously, we enrolled 26 sedentary, middle-aged men (13 dysglycaemic and overweight; 13 normoglycaemic and of healthy weight) into a 12 week, supervised, intensive physical exercise intervention that included two endurance and two resistance sessions each week. Insulin sensitivity was measured as the glucose infusion rate from a euglycaemic-hyperinsulinaemic clamp. In our previous study, we measured maximum oxygen uptake, upper-and lower-body strength and a range of circulating biomarkers, and quantified adipose tissue depots using MRI and magnetic resonance spectroscopy. We have now performed global mRNA sequencing, microarrays and RT-PCR of scWAT and skeletal muscle biopsies, and quantified selected plasma adipokines by ELISA. Results Insulin sensitivity increased similarly in both dysglycaemic (45%) and normoglycaemic (38%) men after 12 weeks of exercise, as reported previously. mRNA sequencing of scWAT revealed 90 transcripts that responded to exercise in dysglycaemic men, whereas only marginal changes were observed in normoglycaemic men. These results were validated using microarrays and RT-PCR. A total of 62 out of 90 transcripts encoded secreted proteins. Overall, 17 transcripts were upregulated and 73 transcripts were downregulated. Downregulated transcripts included several macrophage markers, and were associated with inflammatory and immune-related pathways. Levels of these immune-related transcripts were enhanced in dysglycaemic men vs normoglycaemic men at baseline, but were normalised after the exercise intervention. Principal component and correlation analyses revealed inverse correlations between levels of these immune-related transcripts and insulin sensitivity at baseline, after the intervention, and for the change between baseline and after the intervention. In addition, levels of these transcripts at baseline could predict exercise-induced improvements in insulin sensitivity. Adipokine levels in scWAT (but not in skeletal muscle) were significantly correlated with corresponding plasma adipokine concentrations, as exemplified by leptin, high-molecular-weight adiponectin and secreted frizzledrelated protein 4 (SFRP4). SFRP4 mRNA was the most exercise-responsive transcript in scWAT from dysglycaemic men, and plasma SFRP4 concentrations were reduced in dysglycaemic men, but not in normoglycaemic men, after 12 weeks of exercise.

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Insulin sensitivity, body composition and adipose depots following 12 w combined endurance and strength training in dysglycemic and normoglycemic sedentary men

Abstract: Body composition, fat distribution and insulin sensitivity improved following training in sedentary middle-aged men with and without dysglycemia.

Cited by 62 publications

References 64 publications

Global mRNA sequencing of human skeletal muscle: Search for novel exercise-regulated myokines

Global mRNA sequencing of human skeletal muscle: Search for novel exercise-regulated myokines

Exercise in vivo marks human myotubes in vitro: Training-induced increase in lipid metabolism

Effects of long-term exercise on plasma adipokine levels and inflammation-related gene expression in subcutaneous adipose tissue in sedentary dysglycaemic, overweight men and sedentary normoglycaemic men of healthy weight

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