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Palmitic acid reduces viability and increases production of reactive oxygen species and respiration in rat tendon-derived cells
Palmitic acid reduces viability and increases production of reactive oxygen species and respiration in rat tendon-derived cells
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Length:
20 minutes
Released:
Feb 10, 2023
Format:
Podcast episode
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Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.02.08.527761v1?rss=1
Authors: Konar, S., Hedges, C. P., Callon, K. E., Bolam, S. M., Leung, S., Cornish, J., Naot, D., Musson, D. S.
Abstract:
Clinically, there is a positive correlation between BMI and the risk of tendinopathy. However, the underlying mechanisms are not understood. Dyslipidaemia and increased circulating free fatty acids (FFA) are associated with increased BMI. We hypothesised that increased FFA concentrations negatively affect rat tendon-derived cells (rTDCs) through mitochondrial-mediated mechanisms. rTDCs were isolated and treated with oleic acid (OA), stearic acid (SA), and palmitic acid (PA). Cell viability was assessed using AlamarBlue assay, and gene expression using real-time PCR. Cell respiration and reactive oxygen species (ROS) production were measured using high-resolution respirometry and MitoSox staining. PA transport into the mitochondria was blocked by pre-treatment with 50 M etomoxir. Treatment with SA and PA at 10 g/ml decreased rTDC viability by 40% and 60%, respectively. PA decreased the gene expression of the tendon markers Scx and Tnmd, and increased the expression of Mmp3, Mmp13, and Ptgs2 (encoding Cox-2). FFA treatment increased the expression of Cpt1 and Pdk4, indicating an increase in mitochondrial FFA oxidation. PA, at 10 g/ml, increased cellular respiration and ROS production. Pre-treatment with etomoxir partially inhibited the effects of PA on cell viability, Mmp3 gene expression, ROS production, and cell respiration, but did not affect PA-induced inhibition of Scx or Tnmd expression. We found that increased saturated FFA concentrations in the microenvironment reduce cell viability and alter ROS production, respiration, and gene expression. Blocking PA transport into mitochondria partially reversed the negative effects of PA. Overall, an increase in saturated FFA concentrations may contribute to poor tendon health.
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http://biorxiv.org/cgi/content/short/2023.02.08.527761v1?rss=1
Authors: Konar, S., Hedges, C. P., Callon, K. E., Bolam, S. M., Leung, S., Cornish, J., Naot, D., Musson, D. S.
Abstract:
Clinically, there is a positive correlation between BMI and the risk of tendinopathy. However, the underlying mechanisms are not understood. Dyslipidaemia and increased circulating free fatty acids (FFA) are associated with increased BMI. We hypothesised that increased FFA concentrations negatively affect rat tendon-derived cells (rTDCs) through mitochondrial-mediated mechanisms. rTDCs were isolated and treated with oleic acid (OA), stearic acid (SA), and palmitic acid (PA). Cell viability was assessed using AlamarBlue assay, and gene expression using real-time PCR. Cell respiration and reactive oxygen species (ROS) production were measured using high-resolution respirometry and MitoSox staining. PA transport into the mitochondria was blocked by pre-treatment with 50 M etomoxir. Treatment with SA and PA at 10 g/ml decreased rTDC viability by 40% and 60%, respectively. PA decreased the gene expression of the tendon markers Scx and Tnmd, and increased the expression of Mmp3, Mmp13, and Ptgs2 (encoding Cox-2). FFA treatment increased the expression of Cpt1 and Pdk4, indicating an increase in mitochondrial FFA oxidation. PA, at 10 g/ml, increased cellular respiration and ROS production. Pre-treatment with etomoxir partially inhibited the effects of PA on cell viability, Mmp3 gene expression, ROS production, and cell respiration, but did not affect PA-induced inhibition of Scx or Tnmd expression. We found that increased saturated FFA concentrations in the microenvironment reduce cell viability and alter ROS production, respiration, and gene expression. Blocking PA transport into mitochondria partially reversed the negative effects of PA. Overall, an increase in saturated FFA concentrations may contribute to poor tendon health.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
Released:
Feb 10, 2023
Format:
Podcast episode
Titles in the series (100)
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