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Hyperphosphatemia Contributes to Skeletal Muscle Atrophy in Mice. | LitMetric

Hyperphosphatemia Contributes to Skeletal Muscle Atrophy in Mice.

Int J Mol Sci

Division of Nephrology and Section of Mineral Metabolism, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Published: August 2024

AI Article Synopsis

  • Chronic kidney disease (CKD) leads to various health issues, including high phosphate levels (hyperphosphatemia), which can harm blood vessels and cause muscle atrophy.
  • In experiments with mice, those with CKD or high phosphate diets showed reduced muscle mass and function, confirming that hyperphosphatemia is linked to muscle damage.
  • Direct exposure to high phosphate levels in cultured muscle cells also resulted in muscle atrophy, indicating that high phosphate can independently contribute to muscle injury, particularly in the context of CKD.

Article Abstract

Chronic kidney disease (CKD) is associated with various pathologic changes, including elevations in serum phosphate levels (hyperphosphatemia), vascular calcification, and skeletal muscle atrophy. Elevated phosphate can damage vascular smooth muscle cells and cause vascular calcification. Here, we determined whether high phosphate can also affect skeletal muscle cells and whether hyperphosphatemia, in the context of CKD or by itself, is associated with skeletal muscle atrophy. As models of hyperphosphatemia with CKD, we studied mice receiving an adenine-rich diet for 14 weeks and mice with deletion of Collagen 4a3 (). As models of hyperphosphatemia without CKD, we analyzed mice receiving a high-phosphate diet for three and six months as well as a genetic model for klotho deficiency (/). We found that adenine, , and / mice have reduced skeletal muscle mass and function and develop atrophy. Mice on a high-phosphate diet for six months also had lower skeletal muscle mass and function but no significant signs of atrophy, indicating less severe damage compared with the other three models. To determine the potential direct actions of phosphate on skeletal muscle, we cultured primary mouse myotubes in high phosphate concentrations, and we detected the induction of atrophy. We conclude that in experimental mouse models, hyperphosphatemia is sufficient to induce skeletal muscle atrophy and that, among various other factors, elevated phosphate levels might contribute to skeletal muscle injury in CKD.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11395169PMC
http://dx.doi.org/10.3390/ijms25179308DOI Listing

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