Elevated CO2 Levels Delay Skeletal Muscle Repair by Increasing Fatty Acid Oxidation
Muscle dysfunction often occurs in patients with chronic obstructive pulmonary diseases (COPD) and affects ventilatory and non-ventilatory skeletal muscles. We have previously reported that hypercapnia (elevated CO2 levels) causes muscle atrophy through the activation of the AMPKα2-FoxO3a-MuRF1 path...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2020.630910/full |
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| author | Ermelinda Ceco Diego Celli Samuel Weinberg Masahiko Shigemura Lynn C. Welch Lena Volpe Navdeep S. Chandel Ankit Bharat Ankit Bharat Emilia Lecuona Jacob I. Sznajder |
| author_facet | Ermelinda Ceco Diego Celli Samuel Weinberg Masahiko Shigemura Lynn C. Welch Lena Volpe Navdeep S. Chandel Ankit Bharat Ankit Bharat Emilia Lecuona Jacob I. Sznajder |
| author_sort | Ermelinda Ceco |
| collection | DOAJ |
| description | Muscle dysfunction often occurs in patients with chronic obstructive pulmonary diseases (COPD) and affects ventilatory and non-ventilatory skeletal muscles. We have previously reported that hypercapnia (elevated CO2 levels) causes muscle atrophy through the activation of the AMPKα2-FoxO3a-MuRF1 pathway. In the present study, we investigated the effect of normoxic hypercapnia on skeletal muscle regeneration. We found that mouse C2C12 myoblasts exposed to elevated CO2 levels had decreased fusion index compared to myoblasts exposed to normal CO2. Metabolic analyses of C2C12 myoblasts exposed to high CO2 showed increased oxidative phosphorylation due to increased fatty acid oxidation. We utilized the cardiotoxin-induced muscle injury model in mice exposed to normoxia and 10% CO2 for 21 days and observed that muscle regeneration was delayed. High CO2-delayed differentiation in both mouse C2C12 myoblasts and skeletal muscle after injury and was restored to control levels when cells or mice were treated with a carnitine palmitoyltransfearse-1 (CPT1) inhibitor. Taken together, our data suggest that hypercapnia leads to changes in the metabolic activity of skeletal muscle cells, which results in impaired muscle regeneration and recovery after injury. |
| first_indexed | 2024-12-17T04:58:13Z |
| format | Article |
| id | doaj.art-564ea3e2a2024041a00300a8aeaacdba |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-17T04:58:13Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-564ea3e2a2024041a00300a8aeaacdba2022-12-21T22:02:39ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-01-011110.3389/fphys.2020.630910630910Elevated CO2 Levels Delay Skeletal Muscle Repair by Increasing Fatty Acid OxidationErmelinda Ceco0Diego Celli1Samuel Weinberg2Masahiko Shigemura3Lynn C. Welch4Lena Volpe5Navdeep S. Chandel6Ankit Bharat7Ankit Bharat8Emilia Lecuona9Jacob I. Sznajder10Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDivision of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDivision of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDivision of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDivision of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDivision of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDivision of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDivision of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDivision of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDivision of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDivision of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesMuscle dysfunction often occurs in patients with chronic obstructive pulmonary diseases (COPD) and affects ventilatory and non-ventilatory skeletal muscles. We have previously reported that hypercapnia (elevated CO2 levels) causes muscle atrophy through the activation of the AMPKα2-FoxO3a-MuRF1 pathway. In the present study, we investigated the effect of normoxic hypercapnia on skeletal muscle regeneration. We found that mouse C2C12 myoblasts exposed to elevated CO2 levels had decreased fusion index compared to myoblasts exposed to normal CO2. Metabolic analyses of C2C12 myoblasts exposed to high CO2 showed increased oxidative phosphorylation due to increased fatty acid oxidation. We utilized the cardiotoxin-induced muscle injury model in mice exposed to normoxia and 10% CO2 for 21 days and observed that muscle regeneration was delayed. High CO2-delayed differentiation in both mouse C2C12 myoblasts and skeletal muscle after injury and was restored to control levels when cells or mice were treated with a carnitine palmitoyltransfearse-1 (CPT1) inhibitor. Taken together, our data suggest that hypercapnia leads to changes in the metabolic activity of skeletal muscle cells, which results in impaired muscle regeneration and recovery after injury.https://www.frontiersin.org/articles/10.3389/fphys.2020.630910/fullhypercapniachronic obstructive pulmonary diseasesmuscle differentiationβ-Oxidationcardiotoxin |
| spellingShingle | Ermelinda Ceco Diego Celli Samuel Weinberg Masahiko Shigemura Lynn C. Welch Lena Volpe Navdeep S. Chandel Ankit Bharat Ankit Bharat Emilia Lecuona Jacob I. Sznajder Elevated CO2 Levels Delay Skeletal Muscle Repair by Increasing Fatty Acid Oxidation Frontiers in Physiology hypercapnia chronic obstructive pulmonary diseases muscle differentiation β-Oxidation cardiotoxin |
| title | Elevated CO2 Levels Delay Skeletal Muscle Repair by Increasing Fatty Acid Oxidation |
| title_full | Elevated CO2 Levels Delay Skeletal Muscle Repair by Increasing Fatty Acid Oxidation |
| title_fullStr | Elevated CO2 Levels Delay Skeletal Muscle Repair by Increasing Fatty Acid Oxidation |
| title_full_unstemmed | Elevated CO2 Levels Delay Skeletal Muscle Repair by Increasing Fatty Acid Oxidation |
| title_short | Elevated CO2 Levels Delay Skeletal Muscle Repair by Increasing Fatty Acid Oxidation |
| title_sort | elevated co2 levels delay skeletal muscle repair by increasing fatty acid oxidation |
| topic | hypercapnia chronic obstructive pulmonary diseases muscle differentiation β-Oxidation cardiotoxin |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2020.630910/full |
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