scholarly journals Combined overexpression of SIRT1 and knockout of GCN5 in adult skeletal muscle does not affect glucose homeostasis or exercise performance in mice

2020 ◽  
Vol 318 (2) ◽  
pp. E145-E151 ◽  
Author(s):  
Kristoffer Svensson ◽  
Shahriar Tahvilian ◽  
Vitor F. Martins ◽  
Jessica R. Dent ◽  
Adrianna Lemanek ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Homeostasis ◽  
Mitochondrial Biogenesis ◽  
Exercise Performance ◽  
Wheel Running ◽  
Contractile Function ◽  
Muscle Contractile ◽  
Combined Overexpression ◽  
Voluntary Wheel

Sirtuin 1 (SIRT1) and general control of amino acid synthesis 5 (GCN5) regulate mitochondrial biogenesis via opposing modulation of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) acetylation status and activity. However, the combined contribution of SIRT1 and GCN5 to skeletal muscle metabolism and endurance performance in vivo is unknown. In this study, we investigated the impact of combined skeletal muscle-specific overexpression of SIRT1 and deletion of GCN5 on glucose homeostasis, skeletal muscle mitochondrial biogenesis and function, and metabolic adaptation to endurance exercise training in mice. We generated mice with combined and tamoxifen-inducible skeletal muscle-specific overexpression of SIRT1 and knockout of GCN5 (dTG) and floxed [wild type (WT)] littermates using a Cre-LoxP approach. All mice were treated with tamoxifen at 5–6 wk of age, and 4–7 wk later glucose homeostasis, skeletal muscle contractile function, mitochondrial function, and the effects of 14 days of voluntary wheel running on expression of metabolic proteins and exercise capacity were assessed. There was no difference in oral glucose tolerance, skeletal muscle contractile function, mitochondrial abundance, or maximal respiratory capacity between dTG and WT mice. Additionally, there were no genotype differences in exercise performance and markers of mitochondrial biogenesis after 14 days of voluntary wheel running. These results demonstrate that combined overexpression of SIRT1 and loss of GCN5 in vivo does not promote metabolic remodeling in skeletal muscle of sedentary or exercise-trained mice.

scholarly journals Impact of estrogen deficiency on diaphragm and leg muscle contractile function in female mdx mice

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0249472
Author(s):  
Pangdra Vang ◽  
Cory W. Baumann ◽  
Rebecca Barok ◽  
Alexie A. Larson ◽  
Brendan J. Dougherty ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Strength ◽  
Contractile Function ◽  
Estrogen Deficiency ◽  
Diaphragm Muscle ◽  
Whole Body ◽  
Ventilatory Function ◽  
Fourth Decade ◽  
Muscle Contractile

Female carriers of Duchenne muscular dystrophy (DMD) presenting with DMD symptomology similar to males with DMD, such as skeletal muscle weakness and cardiomyopathy, are termed manifesting carriers. There is phenotypic variability among manifesting carriers including the age of onset, which can range from the first to fourth decade of life. In females, estrogen levels typically begin to decline during the fourth decade of life and estrogen deficiency contributes to loss of muscle strength and recovery of strength following injury. Thus, we questioned whether the decline of estrogen impacts the development of DMD symptoms in females. To address this question, we studied 6–8 month-old homozygous mdx female mice randomly assigned to a sham or ovariectomy (OVX) surgical group. In vivo whole-body plethysmography assessed ventilatory function and diaphragm muscle strength was measured in vitro before and after fatigue. Anterior crural muscles were analyzed in vivo for contractile function, fatigue, and in response to eccentric contraction (ECC)-induced injury. For the latter, 50 maximal ECCs were performed by the anterior crural muscles to induce injury. Body mass, uterine mass, hypoxia-hypercapnia ventilatory response, and fatigue index were analyzed by a pooled unpaired t-test. A two-way ANOVA was used to analyze ventilatory measurements. Fatigue and ECC-injury recovery experiments were analyzed by a two-way repeated-measures ANOVA. Results show no differences between sham and OVX mdx mice in ventilatory function, strength, or recovery of strength after fatigue in the diaphragm muscle or anterior crural muscles (p ≥ 0.078). However, OVX mice had significantly greater eccentric torque loss and blunted recovery of strength after ECC-induced injury compared to sham mice (p ≤ 0.019). Although the results show that loss of estrogen has minimal impact on skeletal muscle contractile function in female mdx mice, a key finding suggests that estrogen is important in muscle recovery in female mdx mice after injury.

Chronic enhancement of neuromuscular activity increases acetylcholinesterase gene expression in skeletal muscle

1995 ◽  
Vol 269 (4) ◽  
pp. C856-C862 ◽  
Author(s):  
H. Sveistrup ◽  
R. Y. Chan ◽  
B. J. Jasmin
Keyword(s):  
Ache Activity ◽  
Wheel Running ◽  
Compensatory Hypertrophy ◽  
Molecular Forms ◽  
Plantaris Muscle ◽  
Neuromuscular Activation ◽  
Neuromuscular Activity ◽  
Acetylcholinesterase Gene ◽  
Voluntary Wheel

We determined levels of mRNA encoding acetylcholinesterase (AChE) in muscles of rats subjected to chronic enhancement of neuromuscular activation. After 8 wk of voluntary wheel running, extensor digitorum longus (EDL) muscles displayed a 72% increase in total AChE activity as a result of a selective threefold increase in the G4 content. Soleus muscles, on the other hand, exhibited a 30% decrease in A12 while displaying a small (33%) increase in total AChE activity. These enzymatic adaptations were paralleled by increases in the levels of AChE mRNAs in both EDL (32%; P < 0.03) and soleus (42%; P < 0.02) muscles. In addition, compensatory hypertrophy of the plantaris muscle increased total AChE activity by 75%. This change was reflected by an elevation in all AChE molecular forms with A12 (89%) and A8 (179%) showing the most prominent increases. Similar to exercise-trained muscles, hypertrophied plantaris muscles displayed an increase in AChE transcripts (25%; P < 0.04). These results indicate that increases in neuromuscular activity modulate expression of the AChE gene in vivo and suggest the involvement of pretranslational regulatory mechanisms in the adaptive response of AChE to enhanced neuromuscular activation.

scholarly journals Voluntary Wheel Running Selectively Augments Insulin-Stimulated Vasodilation in Arterioles from White Skeletal Muscle of Insulin-Resistant Rats

2012 ◽  
Vol 19 (8) ◽  
pp. 729-738 ◽  
Author(s):  
Catherine R. Mikus ◽  
Bruno T. Roseguini ◽  
Grace M. Uptergrove ◽  
E. Matthew Morris ◽  
Randy Scott Rector ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Wheel Running ◽  
Voluntary Wheel Running ◽  
Insulin Resistant ◽  
Voluntary Wheel

Abstract 12231: PECAM1 is Essential for Flow-mediated Gab1 Tyrosine Phosphorylation and Signaling in vitro and in vivo

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Suowen Xu ◽  
Marina Koroleva ◽  
Keigi Fujiwara ◽  
Zheng Gen Jin
Keyword(s):  
Tyrosine Phosphorylation ◽  
Wheel Running ◽  
Tyrosine Phosphatase ◽  
Common Mechanism ◽  
Membrane Localization ◽  
No Production ◽  
Voluntary Wheel Running ◽  
Voluntary Wheel

Introduction: Impaired activation of endothelial nitric oxide (NO) synthase (eNOS) and ensued NO production is a common mechanism of various cardiovascular pathologies, including hypertension and atherosclerosis. Specific signaling cascades, generated by vascular endothelial cells (ECs) in response to laminar flow, modulate EC structure and functions, NO production in particular. We have previously shown that flow-stimulated Gab1 (Grb2-associated binder-1) tyrosine phosphorylation mediates eNOS activation. However, the upstream mechanism that regulates Gab1 tyrosine phosphorylation remains unclear. Hypothesis: We hypothesized that platelet endothelial cell adhesion molecule-1 (PECAM1), a key molecule in an endothelial mechanosensing complex, specifically mediates Gab1 tyrosine phosphorylation and its downstream Akt and eNOS activation in ECs upon flow rather than hepatocyte growth factor (HGF) stimulation. Methods: Western blot, en face staining and voluntary wheel running. Results: Small interfering RNA (siRNA) targeting PECAM1 abolished flow- but not HGF-induced Gab1 tyrosine phosphorylation and Akt, eNOS activation as well as Gab1 membrane translocation. Protein-tyrosine phosphatase SHP2, which has been shown to interact with Gab1, was involved in a flow signaling pathway as well as HGF-induced signaling, as SHP2 siRNA diminished the flow- and HGF-induced Gab1 tyrosine phosphorylation, membrane localization and downstream signaling. Pharmacological inhibition of PI3K by LY294002 decreased flow, but not HGF-mediated Gab1 phosphorylation and membrane localization as well as eNOS activation. Finally, we observed that flow-mediated Gab1 and eNOS phosphorylation in vivo induced by voluntary wheel running was reduced in PECAM1 knockout mice. Conclusions: These results demonstrate a specific role of PECAM1 in flow-mediated Gab1 tyrosine phosphorylation and eNOS signaling in ECs

Differential effects of anesthetics on in vivo skeletal muscle contractile function in the mouse

1996 ◽  
Vol 80 (1) ◽  
pp. 332-340 ◽  
Author(s):  
C. P. Ingalls ◽  
G. L. Warren ◽  
D. A. Lowe ◽  
D. B. Boorstein ◽  
R. B. Armstrong
Keyword(s):  
Skeletal Muscle ◽  
Contractile Function ◽  
Average Power ◽  
Eccentric Contraction ◽  
Peak Torque ◽  
High Dose ◽  
Skeletal Muscle Function ◽  
Contractile Responses ◽  
Time Integral

The purpose of this study was to evaluate the effects of four anesthetic regimens on in vivo contractile function of mouse ankle dorsiflexor muscles. The torque-frequency and torque-velocity relationships were determined for the following anesthetics: fentanyl-droperidol and diazepam (F-d/d); ketamine and xylazine (K/x); pentobarbital sodium (Ps); and methoxyflurane (Mf). Mf, Ps, and F-d/d regimens resulted in comparable contractile responses at low doses, whereas K/x produced a relative depression in isometric contractile function as shown by a decrease in the torque-time integral at the 300-Hz stimulation frequency (-13.9%; P < 0.05). Moreover, K/x caused a shift to the left in the torque-frequency curve as indicated by increases in torque-time integrals at 25 and 50 Hz. Both Ps and F-d/d regimens exhibited dose-dependent effects during the isovelocity contractions. Ps significantly reduced work (-28.7%) and average power (-28.9%) at 800 degrees/s at the high dose. In contrast, F-d/d anesthesia resulted in increases in peak torque (16-20%) and work (15-18%) output at all eccentric contraction velocities at the high dose, whereas average power was increased only at -800 (17%) and -1,000 degrees/s (17%). In conclusion, commonly used anesthetic regimens can affect the contractile response in vivo; K/x and Ps yield smaller torque outputs, whereas Mf and F-d/d consistently produce larger contractile responses. Mf and F-d/d are recommended for use in studying skeletal muscle function in mice in vivo.

scholarly journals Dysfunction of muscle contraction with impaired intracellular Ca2+ handling in skeletal muscle and the effect of exercise training in male db/db mice

2019 ◽  
Vol 126 (1) ◽  
pp. 170-182 ◽  
Author(s):  
Hiroaki Eshima ◽  
Yoshifumi Tamura ◽  
Saori Kakehi ◽  
Kyoko Nakamura ◽  
Nagomi Kurebayashi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Muscle Contraction ◽  
Contractile Function ◽  
Contractile Force ◽  
Contractile Dysfunction ◽  
Muscle Contractile ◽  
Type 2 Diabetic

Type 2 diabetes is characterized by reduced contractile force production and increased fatigability of skeletal muscle. While the maintenance of Ca2+ homeostasis during muscle contraction is a requisite for optimal contractile function, the mechanisms underlying muscle contractile dysfunction in type 2 diabetes are unclear. Here, we investigated skeletal muscle contractile force and Ca2+ flux during contraction and pharmacological stimulation in type 2 diabetic model mice ( db/db mice). Furthermore, we investigated the effect of treadmill exercise training on muscle contractile function. In male db/db mice, muscle contractile force and peak Ca2+ levels were both lower during tetanic stimulation of the fast-twitch muscles, while Ca2+ accumulation was higher after stimulation compared with control mice. While 6 wk of exercise training did not improve glucose tolerance, exercise did improve muscle contractile dysfunction, peak Ca2+ levels, and Ca2+ accumulation following stimulation in male db/db mice. These data suggest that dysfunctional Ca2+ flux may contribute to skeletal muscle contractile dysfunction in type 2 diabetes and that exercise training may be a promising therapeutic approach for dysfunctional skeletal muscle contraction. NEW & NOTEWORTHY The purpose of this study was to examine muscle contractile function and Ca2+ regulation as well as the effect of exercise training in skeletal muscle in obese diabetic mice ( db/db). We observed impairment of muscle contractile force and Ca2+ regulation in a male type 2 diabetic animal model. These dysfunctions in muscle were improved by 6 wk of exercise training.

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