Aerobic and resistance training dependent skeletal muscle plasticity in the colon-26 murine model of cancer cachexia

Khamoui, Andy V.; Park, Bong‐Sup; Kim, Do‐Houn; Yeh, Ming‐Chia; Oh, Seung Taek; Elam, Marcus L.; Jo, Edward; Arjmandi, Bahram H.; Salazar, Gloria; Grant, Samuel C.; Contreras, Robert J.; Lee, Wonjun; Kim, Jeong‐Su

doi:10.1016/j.metabol.2016.01.014

Cited by 72 publications

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“…The marginal influence of resistance training in rodent cancer cachexia was also recently reported by another group of investigators [15]. In contrast, aerobic training has been shown to confer several benefits including maintenance of physical function and reduced hepatosplenomegaly [14]. Furthermore, others reported aerobic exercise to not only inhibit muscle atrophy, but also prolong the survival time of C26 mice [16].…”

Section: Introductionmentioning

confidence: 59%

“…4c). Longitudinal changes in the total body mass of exercisetrained C26 mice were previously reported [14] and Fig. 3 Differential response of total bone mineral content (BMC) and bone mineral density (BMD) to aerobic and resistance training in colon-26 (C26) tumor-induced cachexia.…”

Section: Loss Of Total Bmc and Pelvis Bmd In C26-tumor Induced Cachexiamentioning

confidence: 84%

“…In an effort to improve our understanding of therapeutic exercise applications, we recently investigated the impact of aerobic and resistance training on skeletal muscle plasticity in the colon-26 (C26) mouse model of cancer cachexia [14]. Although resistance training is known to stimulate muscle hypertrophy, we did not find overwhelming evidence of protection by resistance training against cancer-induced muscle atrophy.…”

Section: Introductionmentioning

confidence: 85%

“…Study approval was obtained by the Institutional Animal Care and Use Committee at Florida State University before initiating the project. Physical function measurements, select body composition parameters (total body, lean, and fat mass), and in vitro skeletal muscle data have been previously published [14]. All data pertaining to bone are reported in the present study.…”

Section: Mice and Experimental Designmentioning

confidence: 99%

“…cachexia), DXA-determined total body mass was analyzed by 2-way ANOVA (previously published in [14] and reported here for descriptive purposes only). Preexperiment total body mass was not different between Control and C26 (p > 0.05).…”

Section: Loss Of Total Bmc and Pelvis Bmd In C26-tumor Induced Cachexiamentioning

confidence: 99%

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Bone mineral density and content are differentially impacted by aerobic and resistance training in the colon-26 mouse model of cancer cachexia

et al. 2017

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Background: Cancer cachexia is a debilitating paraneoplastic syndrome featuring unintended weight loss and skeletal muscle atrophy. Evidence suggests that bone health may also be compromised, further limiting mobility and quality of life. Aerobic and resistance training was recently reported to differentially affect skeletal muscle adaptations in cancer cachectic mice. The purpose of this investigation was to assess the effects of aerobic and resistance training on bone mineral density (BMD) and bone mineral content (BMC) in mice with colon-26 (C26) tumor-induced cachexia. Methods: Twelve-month old Balb/c mice were aerobic-trained (wheel running 5 days/week) or resistance-trained (weighted ladder climbing 3days/week) for 8 weeks prior to C26 cell injection, followed by an additional three weeks of exercise. BMD and BMC were assessed pre-and post-training by dual-energy x-ray absorptiometry. Results: Resistance-trained C26 mice lost total BMD by 7% (p = 0.06), which did not occur in aerobic-trained C26 mice. In terms of pelvic bone, both resistance-and aerobic-trained C26 mice had significantly lower BMD values (−12%, p = 0.01 and −6%, p = 0.04, respectively), albeit to a lesser degree in aerobic-trained C26 mice. Furthermore, resistance-trained C26 mice tended to lose total BMC (−12%), whereas aerobic-trained C26 mice maintained total BMC. In mice without C26 tumors, resistance training significantly increased total BMD (+13%, p = 0.001). Conclusions: Aerobic and resistance training may differentially affect bone status in C26 cancer cachexia, with high resistance loading possibly being detrimental to total and pelvis BMD, a region expected to bear significant loading stress and contribute substantially to overall mobility. Because resistance training improved BMD in tumor-free mice, the C26 tumor burden appeared to impair the beneficial effect of resistance training on bone mass.

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Section: Introductionmentioning

confidence: 59%

Section: Loss Of Total Bmc and Pelvis Bmd In C26-tumor Induced Cachexiamentioning

confidence: 84%

Section: Introductionmentioning

confidence: 85%

Section: Mice and Experimental Designmentioning

confidence: 99%

Section: Loss Of Total Bmc and Pelvis Bmd In C26-tumor Induced Cachexiamentioning

confidence: 99%

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Bone mineral density and content are differentially impacted by aerobic and resistance training in the colon-26 mouse model of cancer cachexia

et al. 2017

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Distinct glycolytic pathway regulation in liver, tumour and skeletal muscle of mice with cancer cachexia

Visavadiya

Rossiter

Khamoui

2021

Cell Biochemistry & Function

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Energetically inefficient inter‐organ substrate shuttles are proposed contributors to cachexia‐related weight loss. Here, we examined glycolytic pathway metabolites, enzyme activity and transport proteins in skeletal muscle, liver and tumours of mice with cachexia‐related weight loss induced by colon‐26 cancer cells. Skeletal muscle of cachexic mice had increased [L‐lactate]/[pyruvate], LDH activity and lactate transporter MCT1. Cachexic livers also showed increased MCT1. This is consistent with the proposal that the rate of muscle‐derived lactate shuttling to liver for use in gluconeogenesis is increased, that is, an increased Cori cycle flux in weight‐losing cachexic mice. A second shuttle between liver and tumour may also contribute to disrupted energy balance and weight loss. We found increased high‐affinity glucose transporter GLUT1 in tumours, suggesting active glucose uptake, tumour MCT1 detection and decreased intratumour [L‐lactate]/[pyruvate], implying increased lactate efflux and/or intratumour lactate oxidation. Last, high [L‐lactate]/[pyruvate] and MCT1 in cachexic muscle provides a potential muscle‐derived lactate supply for the tumour (a ‘reverse Warburg effect’), supporting tumour growth and consequent cachexia. Our findings suggest several substrate shuttles among liver, skeletal muscle and tumour contribute to metabolic disruption and weight loss. Therapies that aim to normalize dysregulated substrate shuttling among energy‐regulating tissues may alleviate unintended weight loss in cancer cachexia. Significance of the study Cachexia is a serious complication of cancer characterized by severe weight loss, muscle atrophy and frailty. Cachexia occurs in roughly half of all cancer patients, and in up to 80% of patients with advanced disease. Cachexia independently worsens patient prognosis, lowers treatment efficacy, increases hospitalization cost and length of stay, and accounts for 20‐30% of cancer‐related deaths. There are no effective treatments. Our findings suggest several substrate shuttles among liver, skeletal muscle and tumour contribute to metabolic disruption and weight loss in cancer cachexia. Identifying therapies that normalize dysregulated substrate shuttling among energy‐regulating tissues may protect against cachexia‐related weight loss.

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Progressive resistance exercise prevents muscle strength loss due to muscle atrophy induced by methylmercury systemic intoxication

Gouvêa

Silva

Cabral

et al. 2021

JCSM Clinical Reports

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BackgroundThis study investigated the effects of methylmercury intoxication on mice skeletal muscle subjected or not to progressive resistance training (RT).MethodsFour experimental groups were formed. Control and Con + RT received water and methylmercury (MeHg) and MeHg + RT groups received methylmercury (5 mg/kg/day), via gavage for 14 days. The Con + RT and MeHg + RT animals performed weighted ladder climbing RT, three times a week for 4 weeks. Animal muscle strength and gastrocnemius and soleus cross‐section area, fibrosis, myosin heavy chains (MyHCs), E3‐ligases MAFbx and MuRF1, 20S proteasome (P20S) and LC3‐II content were analysed. In addition, P20S chymotrypsin‐like activity was evaluated.ResultsResistance training protected MeHg + RT mice against strength loss but not against muscle atrophy. The latter appeared to be associated with MyHCs significant content reductions observed in the MeHg and MeHg + RT groups. In soleus muscle, there was an increase in E3‐ligases and P20S levels and P20S activity in both methylmercury groups compared with control ones. This pattern was also observed for gastrocnemius muscle, except for P20S content and activity that decreased. The P‐AKT content decreased in the soleus and gastrocnemius of the MeHg animals while significant elevation of LC3‐II content levels occurred.ConclusionsThe accumulation of methylmercury caused an increase in skeletal muscle MyHCs degradation, resulting in muscle atrophy that was reinforced by the elevated fibrosis area. Although RT did not reverse this condition, maintenance of muscle strength levels in animals submitted to MeHg + RT was detected. We believe that RT somewhat protected MeHg from damage to neural muscle structures, to be further investigated.

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Aerobic and resistance training dependent skeletal muscle plasticity in the colon-26 murine model of cancer cachexia

Cited by 72 publications

References 58 publications

Bone mineral density and content are differentially impacted by aerobic and resistance training in the colon-26 mouse model of cancer cachexia

Bone mineral density and content are differentially impacted by aerobic and resistance training in the colon-26 mouse model of cancer cachexia

Distinct glycolytic pathway regulation in liver, tumour and skeletal muscle of mice with cancer cachexia

Progressive resistance exercise prevents muscle strength loss due to muscle atrophy induced by methylmercury systemic intoxication

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