Skeletal Muscle Adaptation to Exercise Training

Röckl, Katja S.C.; Hirshman, Michael F.; Brandauer, Josef; Fujii, Nobuharu; Witters, Lee A.; Goodyear, Laurie J.

doi:10.2337/db07-0255

Cited by 261 publications

(132 citation statements)

References 57 publications

(73 reference statements)

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“…Recent studies have suggested that reduced muscle AMPK may invoke a fiber-type switch (48) or alter muscle size (49). Therefore, to investigate whether this was the cause for the reduced muscle force during contractions we analyzed the fiber composition of EDL muscle and found that there was no difference in the ratio of type IIA (WT ϭ 12 Ϯ 2%, ␤2 KO ϭ 10 Ϯ 3%) to type IIB fibers (WT ϭ 88 Ϯ 1%, ␤2 KO ϭ 90 Ϯ 3%).…”

Section: ␤2 Ko Mice Have Normal Rates Of Contraction-stimulated Glucomentioning

confidence: 99%

Whole Body Deletion of AMP-activated Protein Kinase β2 Reduces Muscle AMPK Activity and Exercise Capacity

Steinberg

O’Neill

Dzamko

et al. 2010

Journal of Biological Chemistry

146

139

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AMP-activated protein kinase (AMPK) ␤ subunits (␤1 and ␤2) provide scaffolds for binding ␣ and ␥ subunits and contain a carbohydrate-binding module important for regulating enzyme activity. We generated C57Bl/6 mice with germline deletion of AMPK ␤2 (␤2 KO) and examined AMPK expression and activity, exercise capacity, metabolic control during muscle contractions, aminoimidazole carboxamide ribonucleotide (AICAR) sensitivity, and susceptibility to obesity-induced insulin resistance. We find that ␤2 KO mice are viable and breed normally. ␤2 KO mice had a reduction in skeletal muscle AMPK ␣1 and ␣2 expression despite up-regulation of the ␤1 isoform. Heart AMPK ␣2 expression was also reduced but this did not affect resting AMPK ␣1 or ␣2 activities. AMPK ␣1 and ␣2 activities were not changed in liver, fat, or hypothalamus. AICAR-stimulated glucose uptake but not fatty acid oxidation was impaired in ␤2 KO mice. During treadmill running ␤2 KO mice had reduced maximal and endurance exercise capacity, which was associated with lower muscle and heart AMPK activity and reduced levels of muscle and liver glycogen. Reductions in exercise capacity of ␤2 KO mice were not due to lower muscle mitochondrial content or defects in contraction-stimulated glucose uptake or fatty acid oxidation. When challenged with a high-fat diet ␤2 KO mice gained more weight and were more susceptible to the development of hyperinsulinemia and glucose intolerance. In summary these data show that deletion of AMPK ␤2 reduces AMPK activity in skeletal muscle resulting in impaired exercise capacity and the worsening of diet-induced obesity and glucose intolerance.The AMP-activated protein kinase (AMPK) 5 is an evolutionary conserved serine/threonine protein kinase that functions as a metabolic regulatory enzyme at both the intracellular and whole body level (1, 2). As a metabolic stress-sensing enzyme, AMPK is activated through phosphorylation of Thr 172 in the ␣-catalytic subunit by upstream kinases, liver kinase B1 (LKB1) and calcium/calmodulin-dependent kinase kinase in response to physiological processes that consume ATP (exercise) or inhibit ATP production (ischemia or hypoxia) (3). Following activation, AMPK acutely regulates lipid, protein, and carbohydrate metabolism through phosphorylation induced changes that alter enzyme activities by switching off ATP consuming anabolic pathways and switching on ATP generating catabolic pathways (4). In addition to these acute effects, AMPK regulates transcription factors to influence gene expression (4). Modulation of AMPK activity by hormones and cytokines adds a complex layer of regulation allowing energy supply and demand within a cell to be integrated with the energy requirements of the whole organism (5).AMPK functions as an ␣␤␥ heterotrimer where the C terminus of the ␤ isoforms (␤1 and ␤2) contains the subunit-binding sequence that is essential for binding the ␥ and ␣ subunits (6, 7). In addition to their structural role in maintaining the AMPK heterotrimer, AMPK ␤ subunits contain an evolutionary ...

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Section: ␤2 Ko Mice Have Normal Rates Of Contraction-stimulated Glucomentioning

confidence: 99%

Whole Body Deletion of AMP-activated Protein Kinase β2 Reduces Muscle AMPK Activity and Exercise Capacity

Steinberg

O’Neill

Dzamko

et al. 2010

Journal of Biological Chemistry

146

139

View full text Add to dashboard Cite

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“…Type IIb is considered to consist of glycolic fibers, producing a pale, soft, and exudative meat (Wegner et al, 2000). In recent years, a number of key genes regulating muscle fiber type transition have been identified, such as peroxisome proliferator-activated receptor-g coactivator-1a (PGC-1a) (Lin et al, 2002), AMP-activated protein kinase (AMPK) (Röckl et al, 2007), etc.…”

Section: Introductionmentioning

confidence: 99%

Comparisons of different myosin heavy chain types, AMPK, and PGC-1α gene expression in the longissimus dorsi muscles in Bama Xiang and Landrace pigs

Huang

Jiang

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Bama Xiang and Landrace pigs are the local fatty and lean breeds, respectively, in China. We compared differences in carcass traits, meat quality traits, and myosin heavy chain (MyHC) types in the longissimus dorsi muscles between Bama Xiang and Landrace pigs. This was done in pigs of the same age, using real-time PCR, to investigate the relationship between MyHC fiber types and carcass characteristics, meat quality traits, and the key factors regulating muscle fiber type. Bama Xiang pigs exhibited smaller size and slower growth than Landrace pigs (P < 0.01). We found that the superior meat quality, especially the high intramuscular fat (IMF) content in Bama Xiang pig, was related to elevated type I oxidative muscle fiber content (P < 0.01). In contrast, Landrace pig muscle had a higher glycolytic type IIb muscle fiber content (P < 0.01). MyHC I gene expression was significantly positively correlated with backfat thickness and IMF content (P < 0.01). MyHC IIb was significantly negatively correlated with IMF content (P < 0.05), and positively correlated with carcass yield (P < 0.05). AMP-activated protein kinase and peroxisome proliferatoractivated receptor-g coactivator-1a are suggested to be the two key factors regulating muscle fiber type in pigs. Our results indicate that muscle fiber composition is one of the key differences leading to the differences of meat quality between Bama Xiang and Landrace pigs. These results may provide a theoretical basis for further studies of the molecular mechanism underlying the excellent meat quality of the Bama Xiang pig.

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“…The mice completed high levels of voluntary exercise during the 4-week period (8.2 Ϯ 0.8 km/day), which we have previously shown results in significant increases in oxidative muscle fiber types and increases in citrate synthase activity (37)(38)(39)(40)(41). Wheel cage training significantly increased Myo1c and GLUT4 protein in triceps muscle by 1.9-and 2.1-fold, respectively, when compared with sedentary controls (Fig.…”

Section: Myo1c Is Highly Expressed In Oxidative Mouse Skeletalmentioning

confidence: 76%

Myo1c Regulates Glucose Uptake in Mouse Skeletal Muscle

Toyoda

Ding

Witczak

et al. 2011

Journal of Biological Chemistry

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Contraction and insulin promote glucose uptake in skeletal muscle through GLUT4 translocation to cell surface membranes. Although the signaling mechanisms leading to GLUT4 translocation have been extensively studied in muscle, the cellular transport machinery is poorly understood. Myo1c is an actin-based motor protein implicated in GLUT4 translocation in adipocytes; however, the expression profile and role of Myo1c in skeletal muscle have not been investigated. Myo1c protein abundance was higher in more oxidative skeletal muscles and heart. Voluntary wheel exercise (4 weeks, 8.2 ؎ 0.8 km/day), which increased the oxidative profile of the triceps muscle, significantly increased Myo1c protein levels by ϳ2-fold versus sedentary controls. In contrast, high fat feeding (9 weeks, 60% fat) significantly reduced Myo1c by 17% in tibialis anterior muscle. To study Myo1c regulation of glucose uptake, we expressed wild-type Myo1c or Myo1c mutated at the ATPase catalytic site (K111A-Myo1c) in mouse tibialis anterior muscles in vivo and assessed glucose uptake in vivo in the basal state, in response to 15 min of in situ contraction, and 15 min following maximal insulin injection (16.6 units/kg of body weight). Expression of wild-type Myo1c or K111A-Myo1c had no effect on basal glucose uptake. However, expression of wild-type Myo1c significantly increased contraction-and insulin-stimulated glucose uptake, whereas expression of K111A-Myo1c decreased both contraction-stimulated and insulin-stimulated glucose uptake. Neither wild-type nor K111A-Myo1c expression altered GLUT4 expression, and neither affected contraction-or insulin-stimulated signaling proteins. Myo1c is a novel mediator of both insulin-stimulated and contraction-stimulated glucose uptake in skeletal muscle.Glucose uptake in skeletal muscle provides energy for muscle fibers and is also critical in the maintenance of whole body glucose homeostasis. In people with type 2 diabetes, defects in insulin-stimulated glucose uptake in skeletal muscle are a major factor in impaired glucose homeostasis. Therefore, elucidating the molecular mechanisms regulating glucose uptake in muscle has been the focus of considerable research and could eventually lead to the development of new treatments for type 2 diabetes.Contraction and insulin are the major physiological stimulators of glucose uptake in muscle, and both stimuli increase uptake by increasing the number of glucose transporter proteins at the sarcolemma and transverse tubules (1-5). Glucose transporter 4 (GLUT4) is the major glucose transporter protein expressed in skeletal muscle, and in the basal state, it is contained in specialized intracellular vesicular structures. Insulin stimulates GLUT4 translocation in muscle via a distinct, well characterized intracellular signaling cascade that includes phosphorylation of the insulin receptor and insulin receptor substrate-1/2 (IRS-1/2), activation of phosphatidylinositol 3-kinase (PI3-kinase), and phosphorylation of Akt (6). Although the signaling pathways by which muscle con...

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Skeletal Muscle Adaptation to Exercise Training

Cited by 261 publications

References 57 publications

Whole Body Deletion of AMP-activated Protein Kinase β2 Reduces Muscle AMPK Activity and Exercise Capacity

Whole Body Deletion of AMP-activated Protein Kinase β2 Reduces Muscle AMPK Activity and Exercise Capacity

Comparisons of different myosin heavy chain types, AMPK, and PGC-1α gene expression in the longissimus dorsi muscles in Bama Xiang and Landrace pigs

Myo1c Regulates Glucose Uptake in Mouse Skeletal Muscle

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