scholarly journals Spontaneous Physical Activity Downregulates Pax7 in Cancer Cachexia

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Dario Coletti ◽  
Paola Aulino ◽  
Eva Pigna ◽  
Fabio Barteri ◽  
Viviana Moresi ◽  
...  

Emerging evidence suggests that the muscle microenvironment plays a prominent role in cancer cachexia. We recently showed that NF-kB-induced Pax7 overexpression impairs the myogenic potential of muscle precursors in cachectic mice, suggesting that lowering Pax7 expression may be beneficial in cancer cachexia. We evaluated the muscle regenerative potential after acute injury in C26 colon carcinoma tumor-bearing mice and healthy controls. Our analyses confirmed that the delayed muscle regeneration observed in muscles form tumor-bearing mice was associated with a persistent local inflammation and Pax7 overexpression. Physical activity is known to exert positive effects on cachectic muscles. However, the mechanism by which a moderate voluntary exercise ameliorates muscle wasting is not fully elucidated. To verify if physical activity affects Pax7 expression, we hosted control and C26-bearing mice in wheel-equipped cages and we found that voluntary wheel running downregulated Pax7 expression in muscles from tumor-bearing mice. As expected, downregulation of Pax7 expression was associated with a rescue of muscle mass and fiber size. Our findings shed light on the molecular basis of the beneficial effect exerted by a moderate physical exercise on muscle stem cells in cancer cachexia. Furthermore, we propose voluntary exercise as a physiological tool to counteract the overexpression of Pax7 observed in cancer cachexia.

Open Medicine ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. 144-156 ◽  
Author(s):  
Gabriele Ceccarelli ◽  
Laura Benedetti ◽  
Maria Luisa Arcari ◽  
Cecilia Carubbi ◽  
Daniela Galli

AbstractIn the last 15 years, it emerged that the practice of regular physical activity reduces the risks of many diseases (cardiovascular diseases, diabetes, etc.) and it is fundamental in weight control and energy consuming to contrast obesity. Different groups proposed many molecular mechanisms as responsible for the positive effects of physical activity in healthy life. However, many points remain to be clarified. In this mini-review we reported the latest observations on the effects of physical exercise on healthy skeletal and cardiac muscle focusing on muscle stem cells. The last ones represent the fundamental elements for muscle regeneration post injury, but also for healthy muscle homeostasis.Interestingly, in both muscle tissues the morphological consequence of physical activity is a physiological hypertrophy that depends on different phenomena both in differentiated cells and stem cells. The signaling pathways for physical exercise effects present common elements in skeletal and cardiac muscle, like activation of specific transcription factors, proliferative pathways, and cytokines. More recently, post translational (miRNAs) or epigenetic (DNA methylation) modifications have been demonstrated. However, several points remain unresolved thus requiring new research on the effect of exercise on muscle stem cells.


2011 ◽  
Vol 300 (2) ◽  
pp. E392-E401 ◽  
Author(s):  
Gregory J. Morton ◽  
Karl J. Kaiyala ◽  
Jonathan D. Fisher ◽  
Kayoko Ogimoto ◽  
Michael W. Schwartz ◽  
...  

Mechanisms regulating spontaneous physical activity remain poorly characterized despite evidence of influential genetic and acquired factors. We evaluated ambulatory activity and wheel running in leptin-deficient ob/ob mice and in wild-type mice rendered hypoleptinemic by fasting in both the presence and absence of subcutaneous leptin administration. In ob/ob mice, leptin treatment to plasma levels characteristic of wild-type mice acutely increased both ambulatory activity (by 4,000 ± 200 beam breaks/dark cycle, P < 0.05) and total energy expenditure (TEE; by 0.11 ± 0.01 kcal/h during the dark cycle, P < 0.05) in a dose-dependent manner and acutely increased wheel running (+350%, P < 0.05). Fasting potently increased ambulatory activity and wheel running in wild-type mice (AA: +25%, P < 0.05; wheel running: +80%, P < 0.05), and the effect of fasting was more pronounced in ob/ob mice (AA: +400%, P < 0.05; wheel running: +1,600%, P < 0.05). However, unlike what occurred in ad libitum-fed ob/ob mice, physiological leptin replacement attenuated or prevented fasting-induced increases of ambulatory activity and wheel running in both wild-type and ob/ob mice. Thus, plasma leptin is a physiological regulator of spontaneous physical activity, but the nature of leptin's effect on activity is dependent on food availability.


Author(s):  
Dario Coletti ◽  
Sergio Adamo ◽  
Viviana Moresi

Physical activity has multiple beneficial effects in the physiology and pathology of the organism. In particular, we and other groups have shown that running counteracts cancer cachexia in both humans and rodents. The latter are prone to exercise in wheel-equipped cages even at advanced stages of cachexia. However, when we wanted to replicate the experimental model routinely used at the University of Rome in a different laboratory (i.e. at Paris 6 University), we had to struggle with puzzling results due to unpredicted mouse behavior. Here we report the experience and offer the explanation underlying these apparently irreproducible results. The original data are currently used for teaching purposes in undergraduate student classes of biological sciences.


2013 ◽  
Vol 305 (2) ◽  
pp. E171-E182 ◽  
Author(s):  
Juha J. Hulmi ◽  
Bernardo M. Oliveira ◽  
Mika Silvennoinen ◽  
Willem M. H. Hoogaars ◽  
Arja Pasternack ◽  
...  

The importance of adequate levels of muscle size and function and physical activity is widely recognized. Myostatin/activin blocking increases skeletal muscle mass but may decrease muscle oxidative capacity and can thus be hypothesized to affect voluntary physical activity. Soluble activin receptor IIB (sActRIIB-Fc) was produced to block myostatin/activins. Modestly dystrophic mdx mice were injected with sActRIIB-Fc or PBS with or without voluntary wheel running exercise for 7 wk. Healthy mice served as controls. Running for 7 wk attenuated the sActRIIB-Fc-induced increase in body mass by decreasing fat mass. Running also enhanced/restored the markers of muscle oxidative capacity and autophagy in mdx mice to or above the levels of healthy mice. Voluntary running activity was decreased by sActRIIB-Fc during the first 3–4 wk correlating with increased body mass. Home cage physical activity of mice, quantified from the force plate signal, was decreased by sActRIIB-Fc the whole 7-wk treatment in sedentary mice. To understand what happens during the first weeks after sActRIIB-Fc administration, when mice are less active, healthy mice were injected with sActRIIB-Fc or PBS for 2 wk. During the sActRIIB-Fc-induced rapid 2-wk muscle growth period, oxidative capacity and autophagy were reduced, which may possibly explain the decreased running activity. These results show that increased muscle size and decreased markers of oxidative capacity and autophagy during the first weeks of myostatin/activin blocking are associated with decreased voluntary activity levels. Voluntary exercise in dystrophic mice enhances the markers of oxidative capacity and autophagy to or above the levels of healthy mice.


2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Lynn Erin Copes ◽  
Heidi Schutz ◽  
Elizabeth M Dlugsoz ◽  
Wendy Acosta ◽  
Mark A. Chappell ◽  
...  

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