{"doi":"10.1152/ajpcell.00233.2020","title":"Regulation of Lin28a-miRNA <i>let-7b-5p</i> pathway in skeletal muscle cells by peroxisome proliferator-activated receptor delta","abstract":"Lin28a/miRNA let-7b-5p pathway has emerged as a key regulators of energy homeostasis in the skeletal muscle. However, the mechanism through which this pathway is regulated in the skeletal muscle has remained unclear. We have found that 8 wk of aerobic training (Tr) markedly decreased let-7b-5p expression in murine skeletal muscle, whereas high-fat diet (Hfd) increased its expression. Conversely, Lin28a expression, a well-known inhibitor of let-7b-5p, was induced by Tr and decreased by Hfd. Similarly, in human muscle biopsies, Tr increased LIN28 expression and decreased let-7b-5p expression. Bioinformatics analysis of LIN28a DNA sequence revealed that its enrichment in peroxisome proliferator-activated receptor delta (PPARδ) binding sites, which is a well-known metabolic regulator of exercise. Treatment of primary mouse skeletal muscle cells or C2C12 cells with PPARδ activators GW501516 and AICAR increased Lin28a expression. Lin28a and let-7b-5p expression was also regulated by PPARδ coregulators. While PPARγ coactivator-1α (PGC1α) increased Lin28a expression, corepressor NCoR1 decreased its expression. Furthermore, PGC1α markedly reduced the let-7b-5p expression. PGC1α-mediated induction of Lin28a expression was blocked by the PPARδ inhibitor GSK0660. In agreement, Lin28a expression was downregulated in PPARδ knocked-down cells leading to increased let-7b-5p expression. Finally, we show that modulation of the Lin28a- let-7b-5p pathway in muscle cells leads to changes in mitochondrial metabolism in PGC1α dependent fashion. In summary, we demonstrate that Lin28a- let-7b-5p is a direct target of PPARδ in the skeletal muscle, where it impacts mitochondrial respiration.","journal":"American Journal of Physiology-Cell Physiology","year":2020,"id":78810,"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":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":409654,"name":"Tanes Lima","orcid":"0000-0002-6384-1806","position":1,"is_corresponding":false},{"id":410645,"name":"Dimitrius Santiago P.S.F. Guimarães","orcid":null,"position":2,"is_corresponding":false},{"id":409655,"name":"André Gustavo de Oliveira","orcid":"0000-0003-1831-9792","position":3,"is_corresponding":false},{"id":410646,"name":"Bianca Cristine Favero‐Santos","orcid":null,"position":4,"is_corresponding":false},{"id":409656,"name":"Renato Chaves Souto Branco","orcid":"0000-0002-6886-7693","position":5,"is_corresponding":false},{"id":410647,"name":"Rafaela Mariano da Silva Araújo","orcid":null,"position":6,"is_corresponding":false},{"id":410648,"name":"Alvaro F. B. Dantas","orcid":null,"position":7,"is_corresponding":false},{"id":409657,"name":"Alex Castro","orcid":"0000-0002-0298-2672","position":8,"is_corresponding":false},{"id":409658,"name":"Mara Patrícia Traina Chacon‐Mikahil","orcid":"0000-0002-6109-5141","position":9,"is_corresponding":false},{"id":409659,"name":"Elaine Minatel","orcid":"0000-0001-9863-0761","position":10,"is_corresponding":false},{"id":409660,"name":"Murilo Vieira Geraldo","orcid":"0000-0002-9418-6103","position":11,"is_corresponding":false},{"id":409661,"name":"Everardo M. Carneiro","orcid":"0000-0003-3212-369X","position":12,"is_corresponding":false},{"id":409662,"name":"Alice Cristina Rodrigues","orcid":"0000-0002-9005-033X","position":13,"is_corresponding":false},{"id":264228,"name":"Vihang A. Narkar","orcid":"0000-0001-5574-083X","position":14,"is_corresponding":false},{"id":409663,"name":"Leonardo R. Silveira","orcid":"0000-0001-9369-1047","position":15,"is_corresponding":false},{"id":409653,"name":"Hygor N. Araújo","orcid":"0000-0003-1553-2635","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-18T21:50:09.793321Z","pmid":"32697599","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":[]}