Abstract
Low circulating levels of vitamin D were associated with decreased muscle strength and physical performance. Along this line, the present study was aimed to investigate: i) the therapeutic potential of vitamin D in cancer-induced muscle wasting; ii) the mechanisms by which vitamin D affects muscle phenotype in tumor-bearing animals.Rats bearing the AH130 hepatoma showed decreased circulating vitamin D compared to control rats, while muscle vitamin D receptor (VDR) mRNA was up-regulated. Both circulating vitamin D and muscle VDR expression increased after vitamin D administration, without exerting appreciable effects on body weight and muscle mass.The effects of vitamin D on muscle cells were studied in C2C12 myocytes. Vitamin D-treated myoblasts did not differentiate properly, fusing only partially and forming multinucleated structures with aberrant shape and low myosin heavy chain content. Vitamin D treatment resulted in VDR overexpression and myogenin down-regulation. Silencing VDR expression in C2C12 cultures abrogated the inhibition of differentiation exerted by vitamin D treatment.These data suggest that VDR overexpression in tumor-bearing animals contributes to muscle wasting by impairing muscle regenerative program. In this regard, attention should be paid when considering vitamin D supplementation to patients affected by chronic pathologies where muscle regeneration may be involved.
Highlights
Cachexia is a comorbidity of cancer [1] characterized by progressive loss of body weight as well as of skeletal muscle and adipose tissue mass
Consistent with previous in vitro and in vivo observations [23], VitD3 supplementation induced an increase above baseline of vitamin D receptor (VDR) mRNA expression in the tibialis muscle of control animals and further exacerbated the increase occurring in the AH130 hosts (Figure 1C)
Low VitD levels are a frequent feature in advanced cancer patients with cachexia and fatigue [31], while high serum VitD has been associated with low mortality in colorectal cancer patients [32]
Summary
Cachexia is a comorbidity of cancer [1] characterized by progressive loss of body weight as well as of skeletal muscle and adipose tissue mass. More than 50% of all cancer patients develop cachexia. This percentage increases up to 86% during the last 2 weeks of life and about 20% of all cancer deaths can be attributable to cachexia. Cachexia impairs quality of life, as well as tolerance and response to anti-neoplastic treatments (reviewed in [2]). Inflammation and perturbations of hormonal and metabolic homeostasis significantly contribute to the onset and progression of cachexia. In this www.impactjournals.com/oncotarget regard insulin, angiotensin, leptin and myostatin, together with numerous cytokines, including IL6, IL1 and TNFα have been shown to play a role [2, 3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
