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High Concentrations of Nucleotides Prevent Capillary Regression during Hindlimb Unloading by Inhibiting Oxidative

Ryosuke Nakanishi1,2, Nagisa Hashimoto1, Miho Takuwa1

  • 1Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences, 7-10-2, Tomogaoka, Suma-ku, Kobe, Hyogo, 654-0142, Japan.

Acta Histochemica Et Cytochemica
|February 6, 2024
PubMed
Summary

A 5.0% nucleotide diet effectively prevented capillary regression in disused muscles by reducing oxidative stress and enhancing mitochondrial metabolism, preserving muscle health during inactivity.

Keywords:
atrophied musclemitochondrial metabolismmuscle capillarynucleotideoxidative stress

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Area of Science:

  • Exercise physiology
  • Skeletal muscle biology
  • Nutritional biochemistry

Background:

  • Prolonged skeletal muscle inactivity leads to decreased capillary development due to imbalanced angiogenic signals, mitochondrial dysfunction, and oxidative stress.
  • While nucleotides affect muscle atrophy, their dose-dependent impact on capillary regression in disused muscles is not well understood.

Purpose of the Study:

  • To investigate the dose-dependent effect of nucleotide supplementation on capillary regression in hindlimb-unloaded rat skeletal muscle.

Main Methods:

  • Wistar rats were subjected to hindlimb unloading and fed diets with varying nucleotide concentrations (0%, 1.0%, 2.5%, 5.0%).
  • Assessed were reactive oxygen species (ROS) production, mitochondrial enzyme activity, and expression of key metabolic proteins (NAMPT, PGC-1α, CPT-1b).
  • Muscle capillary density was quantified to evaluate the effects of nucleotide supplementation.

Main Results:

  • Hindlimb unloading increased ROS production and decreased mitochondrial enzyme activity, leading to reduced muscle capillary numbers.
  • A 5.0% nucleotide diet attenuated ROS production and prevented the decrease in NAMPT, PGC-1α, and CPT-1b protein expression.
  • The 5.0% nucleotide diet maintained mitochondrial enzyme activity, thereby preventing capillary regression.

Conclusions:

  • Supplementation with a 5.0% nucleotide-containing diet effectively prevents capillary regression in disused skeletal muscle.
  • This protective effect is mediated by the reduction of oxidative stress and the enhancement of mitochondrial metabolism through pathways involving NAMPT and PGC-1α.
  • Nucleotides show promise as a nutritional strategy to counteract muscle deconditioning and maintain vascular integrity during periods of inactivity.