Vitamin D supplementation restores the blunted muscle protein synthesis response in deficient old rats through an impact on ectopic fat deposition

J Nutr Biochem. 2017 Aug;46:30-38. doi: 10.1016/j.jnutbio.2017.02.024. Epub 2017 Apr 8.


We investigated the impact of vitamin D deficiency and repletion on muscle anabolism in old rats. Animals were fed a control (1 IU vitamin D3/g, ctrl, n=20) or a vitamin D-depleted diet (VDD; 0 IU, n=30) for 6 months. A subset was thereafter sacrificed in the control (ctrl6) and depleted groups (VDD6). Remaining control animals were kept for 3 additional months on the same diet (ctrl9), while a part of VDD rats continued on a depleted diet (VDD9) and another part was supplemented with vitamin D (5 IU, VDS9). The ctr16 and VDD6 rats and the ctr19, VDD9 and VDS9 rats were 21 and 24 months old, respectively. Vitamin D status, body weight and composition, muscle strength, weight and lipid content were evaluated. Muscle protein synthesis rate (fractional synthesis rate; FSR) and the activation of controlling pathways were measured. VDD reduced plasma 25(OH)-vitamin D, reaching deficiency (<25 nM), while 25(OH)-vitamin D increased to 118 nM in the VDS group (P<.0001). VDD animals gained weight (P<.05) with no corresponding changes in lean mass or muscle strength. Weight gain was associated with an increase in fat mass (+63%, P<.05), intramyocellular lipids (+75%, P<.05) and a trend toward a decreased plantaris weight (-19%, P=.12). Muscle FSR decreased by 40% in the VDD group (P<.001), but was restored by vitamin D supplementation (+70%, P<.0001). Such changes were linked to an over-phosphorylation of eIF2α. In conclusion, vitamin D deficiency in old rats increases adiposity and leads to reduced muscle protein synthesis through activation of eIF2α. These disorders are restored by vitamin D supplementation.

Keywords: Adiposity; Aging; Muscle protein anabolism; Sarcopenia; Vitamin D; eIF2α signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology
  • Animals
  • Body Composition / drug effects
  • Body Weight / drug effects
  • Dietary Supplements
  • Eating / drug effects
  • Gene Expression / drug effects
  • Lipid Metabolism / drug effects
  • Male
  • Muscle Proteins / biosynthesis*
  • Muscle, Skeletal / metabolism*
  • Organ Size / drug effects
  • Rats, Wistar
  • Signal Transduction
  • Vitamin D / blood
  • Vitamin D / pharmacology*
  • Vitamin D Deficiency / diet therapy
  • Vitamin D Deficiency / metabolism*
  • Vitamin D Deficiency / physiopathology


  • Muscle Proteins
  • Vitamin D