Dose-dependent effects of vitamin D on transdifferentiation of skeletal muscle cells to adipose cells
J Endocrinol April 1, 2013 217 45-58
Kevin J P Ryan, Zoe C T R Daniel, Lucinda J L Craggs, Tim Parr and John M Brameld. john.brameld at nottingham.ac.uk
Division of Nutritional Sciences, School of Biosciences, University of Nottingham, Loughborough, Leics LE12 5RD, UK
Fat infiltration within muscle is one of a number of features of vitamin D deficiency, which leads to a decline in muscle functionality. The origin of this fat is unclear, but one possibility is that it forms from myogenic precursor cells present in the muscle, which transdifferentiate into mature adipocytes. The current study examined the effect of the active form of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), on the capacity of the C2C12 muscle cell line to differentiate towards the myogenic and adipogenic lineages. Cells were cultured in myogenic or adipogenic differentiation media containing increasing concentrations (0, 10−13, 10−11, 10−9, 10−7 or 10−5 M) of 1,25(OH)2D3 for up to 6 days and markers of muscle and fat development measured. Mature myofibres were formed in both adipogenic and myogenic media, but fat droplets were only observed in adipogenic media.
Relative to controls, low physiological concentrations (10−13 and 10−11 M) of 1,25(OH)2D3 increased fat droplet accumulation, whereas high physiological (10−9 M) and supraphysiological concentrations (≥10−7 M) inhibited fat accumulation. This increased accumulation of fat with low physiological concentrations (10−13 and 10−11 M) was associated with a sequential up-regulation of PPARγ2 (PPARG) and FABP4 mRNA, indicating formation of adipocytes, whereas higher concentrations (≥10−9 M) reduced all these effects, and the highest concentration (10−5 M) appeared to have toxic effects.
This is the first study to demonstrate dose-dependent effects of 1,25(OH)2D3 on the transdifferentiation of muscle cells into adipose cells.
Low physiological concentrations (possibly mimicking a deficient state) induced adipogenesis, whereas higher (physiological and supraphysiological) concentrations attenuated this effect.
Received in final form 17 December 2012; Accepted 17 January 2013; online as an Accepted Preprint 17 January 2013
© 2013 Society for Endocrinology
Supp. Figures on-line
PDF is attached at the bottom of this page
- Genes indicate that Obesity causes vitamin D deficiency – Feb 2013 which appears to be the opposite conclusion of this study
- Less weight gain by senior women if vitamin D levels over 30 ng – Kaiser Dec 2012
- Off topic: Can turn obesity on and off in mice with a gene – but not if obese for too long – Oct 2012
- Muscle inflammation 17X more probable if vitamin D deficient – Feb 2013
- Physical performance of seniors increases with vitamin D up to 30 ng – Jan 2013
- Overview Seniors and Vitamin D
- Type 2 muscles, not all muscles, get benefit from Vitamin D - Dec 2012
- Sarcopenia (muscle loss) and Vitamin D wasting away of muscles
- Mobility Disability 1.9X more likely if had low level of vitamin D – May 2012
- Search of Vitamin D Life for sacopenia 193 hits April 2014
- Loss of muscle strength –sarcopenia – one of the suspects is vitamin D – Aug 2012 which has the following chart