Myotubes from lean and severely obese subjects with and without type 2 diabetes respond differently to an in vitro model of exercise

Feng, Yuan; Nikolić, Nataša; Bakke, Siril Skaret; Kase, Eili Tranheim; Guderud, Kari; Hjelmesæth, Jøran; Aas, Vigdis; Rustan, Arild C.; Thoresen, G. Hege

doi:10.1152/ajpcell.00314.2014

Cited by 35 publications

(51 citation statements)

References 58 publications

(77 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[8] showed that lipid oxidation was increased in endurance trained men (athletes trained at a competitive level) compared to untrained men, as measured by lower respiratory exchange ratio. Increased lipid oxidation after exercise is also in line with observations from an in vitro model (electrical pulse stimulation) of myotube exercise [54, 55]. Bourlier et al .…”

Section: Discussionsupporting

confidence: 80%

“…In pre-training myotubes we found increased oxidation and uptake of glucose and lower lipid accumulation in the overweight group compared to the normal weight group, as well as a possible association between lipid accumulation in vitro and insulin sensitivity in vivo . Several previous studies show no significant donor-related differences i basal glucose oxidation in myotubes [54, 57–59], however Gaster [17] observed increased glucose oxidation in myotubes from obese patients with T2D compared to myotubes from lean donors. It was suggested that under certain conditions metabolism of myotubes from diabetic donors relies more on glucose oxidation than myotubes from lean donors [17].…”

Section: Discussionmentioning

confidence: 93%

See 1 more Smart Citation

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

et al. 2017

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 93%

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

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…; Feng et al . ) and our own preliminary experiments. Muscle glycogen content decreased by ∼20% (Fig.…”

Section: Discussionmentioning

confidence: 77%

“…who reported that insulin‐stimulated glycogen synthesis did not change with EPS in primary myotubes from lean subjects and only improved in muscle from severely obese individuals (Feng et al . ). Explanations for this discrepancy may involve differences in the duration of the contraction (48 vs .…”

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Electrical pulse stimulation induces differential responses in insulin action in myotubes from severely obese individuals

Park

Turner

Zheng

et al. 2018

The Journal of Physiology

View full text Add to dashboard Cite

Key points Exercise/exercise training can enhance insulin sensitivity through adaptations in skeletal muscle, the primary site of insulin‐mediated glucose disposal; however, in humans the range of improvement can vary substantially. The purpose of this study was to determine if obesity influences the magnitude of the exercise response in relation to improving insulin sensitivity in human skeletal muscle. Electrical pulse stimulation (EPS; 24 h) of primary human skeletal muscle myotubes improved insulin action in tissue from both lean and severely obese individuals, but responses to EPS were blunted with obesity. EPS improved insulin signal transduction in myotubes from lean but not severely obese subjects and increased AMP accumulation and AMPK Thr172 phosphorylation, but to a lesser degree in myotubes from the severely obese. These data reveal that myotubes of severely obese individuals enhance insulin action and stimulate exercise‐responsive molecules with contraction, but in a manner and magnitude that differs from lean subjects. Abstract Exercise/muscle contraction can enhance whole‐body insulin sensitivity; however, in humans the range of improvements can vary substantially. In order, to determine if obesity influences the magnitude of the exercise response, this study compared the effects of electrical pulse stimulation (EPS)‐induced contractile activity upon primary myotubes derived from lean and severely obese (BMI ≥ 40 kg/m2) women. Prior to muscle contraction, insulin action was compromised in myotubes from the severely obese as was evident from reduced insulin‐stimulated glycogen synthesis, glucose oxidation, glucose uptake, insulin signal transduction (IRS1, Akt, TBC1D4), and insulin‐stimulated GLUT4 translocation. EPS (24 h) increased AMP, IMP, AMPK Thr172 phosphorylation, PGC1α content, and insulin action in myotubes of both the lean and severely obese subjects. However, despite normalizing indices of insulin action to levels seen in the lean control (non‐EPS) condition, responses to EPS were blunted with obesity. EPS improved insulin signal transduction in myotubes from lean but not severely obese subjects and EPS increased AMP accumulation and AMPK Thr172 phosphorylation, but to a lesser degree in myotubes from the severely obese. These data reveal that myotubes of severely obese individuals enhance insulin action and stimulate exercise‐responsive molecules with contraction, but in a manner and magnitude that differs from lean subjects.

show abstract

Skeletal muscle energy metabolism in obesity

Mengeste

Rustan

Lund

2021

Obesity

Self Cite

View full text Add to dashboard Cite

Comparing energy metabolism in human skeletal muscle and primary skeletal muscle cells in obesity, while focusing on glucose and fatty acid metabolism, shows many common changes. Insulin‐mediated glucose uptake in skeletal muscle and primary myotubes is decreased by obesity, whereas differences in basal glucose metabolism are inconsistent among studies. With respect to fatty acid metabolism, there is an increased uptake and storage of fatty acids and a reduced complete lipolysis, suggesting alterations in lipid turnover. In addition, fatty acid oxidation is decreased, probably at the level of complete oxidation, as normalβ‐oxidation may be enhanced in obesity, which indicates mitochondrial dysfunction. Metabolic changes in skeletal muscle with obesity promote metabolic inflexibility, ectopic lipid accumulation, and formation of toxic lipid intermediates. Skeletal muscle also acts as an endocrine organ, secreting myokines that participate in interorgan cross talk. This review highlights interventions and some possible targets for treatment through action on skeletal muscle energy metabolism. Effects of exercise in vivo on obesity have been compared with simulation of endurance exercise in vitro on myotubes (electrical pulse stimulation). Possible pharmaceutical targets, including signaling pathways and drug candidates that could modify lipid storage and turnover or increase mitochondrial function or cellular energy expenditure through adaptive thermogenic mechanisms, are discussed.

show abstract

Myotubes from lean and severely obese subjects with and without type 2 diabetes respond differently to an in vitro model of exercise

Abstract: Feng YZ, Nikolić N, Bakke SS, Kase ET, Guderud K, Hjelmesaeth J, Aas V, Rustan AC, Thoresen GH. Myotubes from lean and severely obese subjects with and without type 2 diabetes respond differently to an in vitro model of exercise.

Cited by 35 publications

References 58 publications

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

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

Electrical pulse stimulation induces differential responses in insulin action in myotubes from severely obese individuals

Skeletal muscle energy metabolism in obesity

Contact Info

Product

Resources

About