Resistance Exercise’s Ability to Reverse Cancer-Induced Anabolic Resistance

Montalvo, Ryan; Hardee, Justin P.; VanderVeen, Brandon N.; Carson, James A.

doi:10.1249/jes.0000000000000159

Cited by 23 publications

(48 citation statements)

References 50 publications

(201 reference statements)

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“…These same muscles when interrogated for proteins implied in AKT pathway indicated no AKT activation, because AKT, 4EBP-1, mTOR and S6K were no more phosphorylated upon running (Figure S7). This can be explained by “anabolic resistance”, typical of cachexia [41]. Only the expression of musclin was partially recovered in gastrocnemius from trained C26-bearing mice (Figure 6f).…”

Section: Resultsmentioning

confidence: 99%

Musclin, A Myokine Induced by Aerobic Exercise, Retards Muscle Atrophy During Cancer Cachexia in Mice

Cecconi

Forti

Chiappa

et al. 2019

Cancers

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Physical activity improves the prognosis of cancer patients, partly by contrasting the associated muscle wasting (cachexia), through still unknown mechanisms. We asked whether aerobic exercise causes secretion by skeletal muscles of proteins (myokines) that may contrast cachexia. Media conditioned by peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α)-expressing myotubes, reproducing some metabolic adaptations of aerobic exercise, as increased mitochondrial biogenesis and oxidative phosphorylation, restrained constitutively active Forkhead box-containing subfamily O3 (caFoxO3)-induced proteolysis. Microarray analysis identified amphiregulin (AREG), natriuretic peptide precursor B (NppB), musclin and fibroblast growth factor 18 (FGF18) as myokines highly induced by PGC1α. Notably, only musclin tended to be low in muscle of mice with a rare human renal carcinoma; it was reduced in plasma and in muscles of C26-bearing mice and in atrophying myotubes, where PGC1α expression is impaired. Therefore, we electroporated the Tibialis Anterior (TA) of C26-bearing mice with musclin or (its receptor) natriuretic peptide receptor 3 (Npr3)-encoding plasmids and found a preserved fiber area, as a result of restrained proteolysis. Musclin knockout (KO) mice lose more muscle tissue during growth of two distinct cachexia-causing tumors. Running protected C26-bearing mice from cachexia, not changing tumor growth, and rescued the C26-induced downregulation of musclin in muscles and plasma. Musclin expression did not change in overloaded plantaris of mice, recapitulating partially muscle adaptations to anaerobic exercise. Musclin might, therefore, be beneficial to cancer patients who cannot exercise and are at risk of cachexia and may help to explain how aerobic exercise alleviates cancer-induced muscle wasting.

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Section: Resultsmentioning

confidence: 99%

Musclin, A Myokine Induced by Aerobic Exercise, Retards Muscle Atrophy During Cancer Cachexia in Mice

Cecconi

Forti

Chiappa

et al. 2019

Cancers

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“…Anabolic resistance, the inability for anabolic stimuli to induce muscle protein synthesis, has been investigated as a driver of age-related sarcopenia (61, 62) and disuse atrophy (31). While anabolic resistance has been reported in cancer patients (56, 63), further investigation is needed to determine the mechanistic underpinnings of this resistance, and to identify the upstream mediators responsible for suppressed anabolic signaling in cachectic muscle (64). Protein degradation is also a tightly regulated process mediated by ubiquitin-proteasomal activation and proteasomal-autophagy-lysosomal pathways (65).…”

Section: Cancer-induced Disruption To Skeletal Muscle and Sexual Dimorpmentioning

confidence: 99%

“…Resistance exercise is a non-pharmacological intervention that can modulate muscle fiber composition, protein turnover, oxidative phosphorylation, and hormones, and it has been extensively reviewed (64, 99, 100). Resistance exercise can benefit the cancer patient’s quality of life and physical function (11, 99–102).…”

Section: Potential Therapeutic Interventionsmentioning

confidence: 99%

Understanding sex differences in the regulation of cancer-induced muscle wasting

Montalvo

Counts

Carson

2018

Current Opinion in Supportive &Amp; Palliative Care

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“…For decades now, endurance and resistance exercise have been proposed as promising therapies as they broadly impact chronic inflammation, metabolic homeostasis, and muscle protein turnover ( Al-Majid and McCarthy, 2001 ; Montalvo et al, 2018 ). There are barriers to exercise as a therapeutic for cancer cachexia as it is unlikely that a level of exercise to induce muscle mass can be performed by patients with debilitating conditions like cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Others have demonstrated that TNF-α plays a key role in cancer and DOX-induced skeletal muscle dysfunction ( Hardin et al, 2008 ; Gilliam et al, 2009 , 2011 ). While disrupted protein turnover has been a central regulator of cancer-induced cachexia ( White et al, 2013 ; Montalvo et al, 2018 ; Counts et al, 2020 ), there is little evidence to suggest chemotherapy impacts muscle in this same way.…”

Section: Cancer and Chemotherapy-induced Cachexia Overviewmentioning

confidence: 99%

The Impact of Immune Cells on the Skeletal Muscle Microenvironment During Cancer Cachexia

2020

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Progressive weight loss combined with skeletal muscle atrophy, termed cachexia, is a common comorbidity associated with cancer that results in adverse consequences for the patient related to decreased chemotherapy responsiveness and increased mortality. Cachexia’s complexity has provided a barrier for developing successful therapies to prevent or treat the condition, since a large number of systemic disruptions that can regulate muscle mass are often present. Furthermore, considerable effort has focused on investigating how tumor derived factors and inflammatory mediators directly signal skeletal muscle to disrupt protein turnover regulation. Currently, there is developing appreciation for understanding how cancer alters skeletal muscle’s complex microenvironment and the tightly regulated interactions between multiple cell types. Skeletal muscle microenvironment interactions have established functions in muscle response to regeneration from injury, growth, aging, overload-induced hypertrophy, and exercise. This review explores the growing body of evidence for immune cell modulation of the skeletal muscle microenvironment during cancer-induced muscle wasting. Emphasis is placed on the regulatory network that integrates physiological responses between immune cells with other muscle cell types including satellite cells, fibroblast cells, and endothelial cells to regulate myofiber size and plasticity. The overall goal of this review is to provide an understanding of how different cell types that constitute the muscle microenvironment and their signaling mediators contribute to cancer and chemotherapy-induced muscle wasting.

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Resistance Exercise’s Ability to Reverse Cancer-Induced Anabolic Resistance

Cited by 23 publications

References 50 publications

Musclin, A Myokine Induced by Aerobic Exercise, Retards Muscle Atrophy During Cancer Cachexia in Mice

Musclin, A Myokine Induced by Aerobic Exercise, Retards Muscle Atrophy During Cancer Cachexia in Mice

Understanding sex differences in the regulation of cancer-induced muscle wasting

The Impact of Immune Cells on the Skeletal Muscle Microenvironment During Cancer Cachexia

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