Mass-dependent decline of skeletal muscle function in cancer cachexia

2006 ◽  
Vol 33 (5) ◽  
pp. 691-693 ◽  
Author(s):  
Marchel Gorselink ◽  
Stefan F.C. Vaessen ◽  
Laurens G. van der Flier ◽  
Inge Leenders ◽  
Diane Kegler ◽  
...  
2018 ◽  
Vol 124 (3) ◽  
pp. 684-695 ◽  
Author(s):  
Brandon N. VanderVeen ◽  
Justin P. Hardee ◽  
Dennis K. Fix ◽  
James A. Carson

While cancer-induced skeletal muscle wasting has been widely investigated, the drivers of cancer-induced muscle functional decrements are only beginning to be understood. Decreased muscle function impacts cancer patient quality of life and health status, and several potential therapeutics have failed in clinical trials due to a lack of functional improvement. Furthermore, systemic inflammation and intrinsic inflammatory signaling’s role in the cachectic disruption of muscle function requires further investigation. We examined skeletal muscle functional properties during cancer cachexia and determined their relationship to systemic and intrinsic cachexia indices. Male ApcMin/+ (MIN) mice were stratified by percent body weight loss into weight stable (WS; <5% loss) or cachectic (CX; >5% loss). Age-matched C57BL/6 littermates served as controls. Tibialis anterior (TA) twitch properties, tetanic force, and fatigability were examined in situ. TA protein and mRNA expression were examined in the nonstimulated leg. CX decreased muscle mass, tetanic force (Po), and specific tetanic force (sPo). Whole body and muscle fatigability were increased in WS and CX. CX had slower contraction rates, +dP/d t and −dP/d t, which were inversely associated with muscle signal transducer and activator of transcription 3 ( STAT3) and p65 activation. STAT3 and p65 activation were also inversely associated with Po. However, STAT3 was not related to sPo or fatigue. Muscle suppressor of cytokine signaling 3 mRNA expression was negatively associated with TA weight, Po, and sPo but not fatigue. Our study demonstrates that multiple functional deficits that occur with cancer cachexia are associated with increased muscle inflammatory signaling. Notably, muscle fatigability is increased in the MIN mouse before cachexia development. NEW & NOTEWORTHY Recent studies have identified decrements in skeletal muscle function during cachexia. We have extended these studies by directly relating decrements in muscle function to established cachexia indices. Our results demonstrate that a slow-fatigable contractile phenotype is developed during the progression of cachexia that coincides with increased muscle inflammatory signaling. Furthermore, regression analysis identified predictors of cancer-induced muscle dysfunction. Last, we report the novel finding that whole body and muscle fatigability were increased before cachexia development.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
C. Homer-Bouthiette ◽  
L. Xiao ◽  
Marja M. Hurley

AbstractFibroblast growth factor 2 (FGF2) is important in musculoskeletal homeostasis, therefore the impact of reduction or Fgf2 knockout on skeletal muscle function and phenotype was determined. Gait analysis as well as muscle strength testing in young and old WT and Fgf2KO demonstrated age-related gait disturbances and reduction in muscle strength that were exacerbated in the KO condition. Fgf2 mRNA and protein were significantly decreased in skeletal muscle of old WT compared with young WT. Muscle fiber cross-sectional area was significantly reduced with increased fibrosis and inflammatory infiltrates in old WT and Fgf2KO vs. young WT. Inflammatory cells were further significantly increased in old Fgf2KO compared with old WT. Lipid-related genes and intramuscular fat was increased in old WT and old Fgf2KO with a further increase in fibro-adipocytes in old Fgf2KO compared with old WT. Impaired FGF signaling including Increased β-Klotho, Fgf21 mRNA, FGF21 protein, phosphorylated FGF receptors 1 and 3, was observed in old WT and old Fgf2KO. MAPK/ ERK1/2 was significantly increased in young and old Fgf2KO. We conclude that Fgf2KO, age-related decreased FGF2 in WT mice, and increased FGF21 in the setting of impaired Fgf2 expression likely contribute to impaired skeletal muscle function and sarcopenia in mice.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohammad Z. Darabseh ◽  
Thomas M. Maden-Wilkinson ◽  
George Welbourne ◽  
Rob C. I. Wüst ◽  
Nessar Ahmed ◽  
...  

AbstractCigarette smoking has a negative effect on respiratory and skeletal muscle function and is a risk factor for various chronic diseases. To assess the effects of 14 days of smoking cessation on respiratory and skeletal muscle function, markers of inflammation and oxidative stress in humans. Spirometry, skeletal muscle function, circulating carboxyhaemoglobin levels, advanced glycation end products (AGEs), markers of oxidative stress and serum cytokines were measured in 38 non-smokers, and in 48 cigarette smokers at baseline and after 14 days of smoking cessation. Peak expiratory flow (p = 0.004) and forced expiratory volume in 1 s/forced vital capacity (p = 0.037) were lower in smokers compared to non-smokers but did not change significantly after smoking cessation. Smoking cessation increased skeletal muscle fatigue resistance (p < 0.001). Haemoglobin content, haematocrit, carboxyhaemoglobin, total AGEs, malondialdehyde, TNF-α, IL-2, IL-4, IL-6 and IL-10 (p < 0.05) levels were higher, and total antioxidant status (TAS), IL-12p70 and eosinophil numbers were lower (p < 0.05) in smokers. IL-4, IL-6, IL-10 and IL-12p70 had returned towards levels seen in non-smokers after 14 days smoking cessation (p < 0.05), and IL-2 and TNF-α showed a similar pattern but had not yet fully returned to levels seen in non-smokers. Haemoglobin, haematocrit, eosinophil count, AGEs, MDA and TAS did not significantly change with smoking cessation. Two weeks of smoking cessation was accompanied with an improved muscle fatigue resistance and a reduction in low-grade systemic inflammation in smokers.


2009 ◽  
Vol 602 (1) ◽  
pp. 143-147 ◽  
Author(s):  
Benoît Giannesini ◽  
Marguerite Izquierdo ◽  
Yann Le Fur ◽  
Patrick J. Cozzone ◽  
Marc Verleye ◽  
...  

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Michael D. Tarpey ◽  
Adam J. Amorese ◽  
Elizabeth R. LaFave ◽  
Everett C. Minchew ◽  
Kelsey H. Fisher-Wellman ◽  
...  

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