{"doi":"10.3389/fphys.2020.630910","title":"Elevated CO2 Levels Delay Skeletal Muscle Repair by Increasing Fatty Acid Oxidation","abstract":"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 CO 2 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 CO 2 levels had decreased fusion index compared to myoblasts exposed to normal CO 2 . Metabolic analyses of C2C12 myoblasts exposed to high CO 2 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% CO 2 for 21 days and observed that muscle regeneration was delayed. High CO 2 -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.","journal":"Frontiers in Physiology","year":2021,"id":186839,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9549,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":745644,"name":"Diego Celli","orcid":"0000-0002-8545-8664","position":1,"is_corresponding":false},{"id":230870,"name":"Samuel E. Weinberg","orcid":"0000-0002-9532-7051","position":2,"is_corresponding":false},{"id":378861,"name":"Masahiko Shigemura","orcid":"0000-0001-7767-6584","position":3,"is_corresponding":false},{"id":424797,"name":"Lynn C. Welch","orcid":"0000-0003-1666-3696","position":4,"is_corresponding":false},{"id":745645,"name":"Lena Volpe","orcid":"0000-0002-3213-0710","position":5,"is_corresponding":false},{"id":104272,"name":"Navdeep S. Chandel","orcid":"0000-0001-7208-3886","position":6,"is_corresponding":false},{"id":232806,"name":"Ankit Bharat","orcid":"0000-0002-1248-0457","position":7,"is_corresponding":false},{"id":468022,"name":"Emilia Lecuona","orcid":"0000-0003-4387-1386","position":8,"is_corresponding":false},{"id":365035,"name":"Jacob I. Sznajder","orcid":"0000-0002-2089-4764","position":9,"is_corresponding":false},{"id":601346,"name":"Ermelinda Ceco","orcid":null,"position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-18T23:48:51.315888Z","pmid":"33551852","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}