Vitamin D3 boosts anabolic effect of leucine

Adding the amino acid leucine to protein-rich meals is perhaps the most effective supplementation strategy for strength athletes seeking to speed up muscle growth. Researchers at Clermont Universite in France have discovered that the higher the concentration of vitamin D3 in the blood, the greater the anabolic effect of leucine.
Adding the amino acid leucine to protein-rich meals is perhaps the most effective supplementation strategy for strength athletes seeking to speed up muscle growth. Researchers at Clermont Universite in France have discovered that the higher the concentration of vitamin D3 in the blood, the greater the anabolic effect of leucine.

The researchers exposed C2C12 muscle cells in test tubes to leucine, insulin and varying concentrations of 1,25(OH)2-vitamin D3, which also goes by the name of calcitriol. This is the active form of vitamin D.

The researchers also added labelled valine to the test tubes, so they could see whether the muscle cells built the valine into their protein structures. This enabled them to measure the anabolic effect of the leucine-insulin cocktail. The more 1,25(OH)2-vitamin D3 there was in the test tubes, the greater the anabolic effect.

When the researchers looked closely at the production and activity of anabolic signal proteins, they noticed that 1,25(OH)2-vitamin D3 made the insulin receptor more sensitive. The greater the concentration of 1,25(OH)2-vitamin D3, the greater the activity of anabolic signal proteins such as Akt, GSK3, p70-S6K and 4EBP1.

The figures above reveal the way in which 1,25(OH)2-vitamin D3 gets the muscle cell’s anabolic machinery to work harder. Vitamin D3 induces muscle cells to manufacture more insulin receptors.

At the same time the muscle cells also produce more vitamin-D receptors as a result of exposure to 1,25(OH)2-vitamin D3, an effect that other researchers had already observed. [Endocrinol Metab Clin North Am. 2010 Jun;39(2):255-69.]

“The transcriptional induction of these genes as well as a potentiation of the insulin and leucine action on key related proteins is likely one of the central mechanisms of action of vitamin D on skeletal muscle anabolism”, the researchers write. “Overall, our data open up perspectives for potentially valuable nutritional interventions coupling vitamin D and amino acid supplementation, mainly in situations like sarcopenia where vitamin D and amino acid response is deficient, to support muscle fiber protein synthesis.”

The research was funded by Danone.

1,25(OH)2 -vitamin D3 enhances the stimulating effect of leucine and insulin on protein synthesis rate through Akt/PKB and mTOR mediated pathways in murine C2C12 skeletal myotubes.

Salles J, Chanet A, Giraudet C, Patrac V, Pierre P, Jourdan M, Luiking YC, Verlaan S, Migné C, Boirie Y, Walrand S.
Source

Clermont Université, Université d’Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand, France; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont-Ferrand, France.

Abstract

SCOPE:

In recent years, there has been a growing body of evidence pointing to an effect of vitamin D on muscle mass and function. Our aim was to investigate the combined effect of 1,25(OH)2 -vitamin D3 (1,25(OH)2 D3 ) with anabolic factors insulin and leucine on protein fractional synthesis rate (FSR) and regulation in the mouse C2C12 myotube.

METHODS AND RESULTS:

After differentiation, myotubes were cultured in 1,25(OH)2 D3 solutions at 0, 1, or 10 nM for 72 h. Cells were treated by l-[1-13 C]valine and puromycin in presence or not of leucine and insulin, and protein FSR was determined by measuring tracer enrichments and puromycin incorporation in proteins, respectively. Protein expression and phosphorylation state of insulin receptor (IR), Akt, GSK3, mTOR, p70 S6 kinase, rpS6, and 4EBP1 were measured by Western blot. Transcript levels of IR and 1,25(OH)2 D3 receptor (VDR) were determined by qPCR. 1,25(OH)2 D3 (10 nM) with leucine and insulin increased protein FSR in C2C12 myotubes (14-16%). IR and VDR mRNA expression was increased with 1,25(OH)2 D3 treatment. The Akt/mTOR-dependent pathway was activated by insulin and leucine and further enhanced by 1,25(OH)2 D3.

CONCLUSION:

1,25(OH)2 D3 sensitizes the Akt/mTOR-dependant pathway to the stimulating effect of leucine and insulin, resulting in a further activation of protein synthesis in murine C2C12 skeletal myotubes.

© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

KEYWORDS:

1,25(OH)2-vitamin D3, Akt/mTOR pathway, C2C12 myotubes, Protein synthesis rate, Skeletal muscle

PMID: 23929734 [PubMed - as supplied by publisher]

Source: http://www.ncbi.nlm.nih.gov/pubmed/23929734