{"doi":"10.1002/jcsm.70269","title":"Dual Roles of Adipose Tissue in Skeletal Muscle Regeneration: Pro‐Regenerative Versus Maladaptive","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:p>Skeletal muscle accounts for approximately 40% of total body mass and is essential for locomotion, metabolic regulation and systemic homeostasis. Adipose tissue is increasingly recognized as an active component of the muscle's regenerative microenvironment. During muscle repair, adipose tissue contributes to local metabolic support and paracrine signalling, but its effects are highly context dependent. Tightly regulated presence of adipose tissue accompanies effective regeneration, whereas excessive or dysregulated ectopic fat accumulation leads to persistent functional impairment. This review synthesizes recent experimental and translational studies investigating the cellular origins, regulatory mechanisms and functional consequences of adipose tissue during skeletal muscle repair. We propose three potential therapeutic directions to improve pathological muscle repair by modulation of the adipose‐related intramuscular regenerative microenvironment: (1) targeted modulation of fibro‐adipogenic progenitors (FAPs) to curb pathological adipogenesis and fibrosis while leveraging beneficial mediators such as adiponectin and leptin; (2) adipose‐derived stem cell transplantation and exosome‐based approaches to deliver multipotent cells and remodel the repair microenvironment; and (3) induction of adipose browning to enhance energy availability, immune tone and vascularization while recognizing its context‐dependent liabilities. Together, these strategies position adipose tissue as a plastic and environment‐sensitive regulator of muscle regeneration and provide a framework for precision interventions to improve structural and functional outcomes.</jats:p>","journal":"Journal of Cachexia, Sarcopenia and Muscle","year":2026,"id":659014,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":94192,"name":"Feng Lu","orcid":"0000-0003-3933-8490","position":1,"is_corresponding":false},{"id":1720359,"name":"Junrong Cai","orcid":null,"position":2,"is_corresponding":false},{"id":1720358,"name":"Chongxuan Lu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Dual Roles of Adipose Tissue in Skeletal Muscle Regeneration: Pro‐Regenerative Versus Maladaptive","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:p>Skeletal muscle accounts for approximately 40% of total body mass and is essential for locomotion, metabolic regulation and systemic homeostasis. Adipose tissue is increasingly recognized as an active component of the muscle's regenerative microenvironment. During muscle repair, adipose tissue contributes to local metabolic support and paracrine signalling, but its effects are highly context dependent. Tightly regulated presence of adipose tissue accompanies effective regeneration, whereas excessive or dysregulated ectopic fat accumulation leads to persistent functional impairment. This review synthesizes recent experimental and translational studies investigating the cellular origins, regulatory mechanisms and functional consequences of adipose tissue during skeletal muscle repair. We propose three potential therapeutic directions to improve pathological muscle repair by modulation of the adipose‐related intramuscular regenerative microenvironment: (1) targeted modulation of fibro‐adipogenic progenitors (FAPs) to curb pathological adipogenesis and fibrosis while leveraging beneficial mediators such as adiponectin and leptin; (2) adipose‐derived stem cell transplantation and exosome‐based approaches to deliver multipotent cells and remodel the repair microenvironment; and (3) induction of adipose browning to enhance energy availability, immune tone and vascularization while recognizing its context‐dependent liabilities. Together, these strategies position adipose tissue as a plastic and environment‐sensitive regulator of muscle regeneration and provide a framework for precision interventions to improve structural and functional outcomes.</jats:p>","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41995010","pmcid":"PMC13088154","openalex_id":"https://openalex.org/W7154712083","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"82472585","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81901976","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82372544","title":null},{"funder_name":"Natural Science Foundation of Guangdong Province","grant_id":"2023A1515011741","title":null},{"funder_name":"Guangzhou Science and Technology Program","grant_id":"2023A04J2348","title":null},{"funder_name":"Nanfang Hospital's Outstanding Young Talent Cultivation Program","grant_id":"K50906009","title":null},{"funder_name":"Nanfang Hospital's Outstanding Young Talent Cultivation Program","grant_id":"K50304020","title":null},{"funder_name":"Nanfang Hospital's Scientific Research Development Fund","grant_id":"K51701101","title":null}],"total_grants":8,"fwci":8.0712,"citation_percentile":0.97598466,"influential_citations":0,"citation_trend":[{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1002/jcsm.70269","host_type":"journal"},{"url":"https://doi.org/10.1002/jcsm.70269","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcsm.70269","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jcsm.70269","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41995010","host_type":"repository"},{"url":"https://doaj.org/article/22790c3d6093408ea79a0c0b0e07bcdb","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13088154/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC13088154","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC13088154?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Muscle Physiology and Disorders","Mesenchymal stem cell research","Adipose Tissue and Metabolism","Humans","Muscle, Skeletal","Regeneration","Adipose Tissue","Animals"],"mesh_terms":["Adipose Tissue","Animals","Humans","Regeneration","Muscle, Skeletal"],"keywords":["Adipose tissue","Skeletal muscle","Paracrine signalling","Myokine","Adipogenesis","Adiponectin","Adipokine","Regeneration (biology)","Fibrosis","Browning","Adipokines","Fatty Infiltration","Skeletal Muscle Repair","Adipose‐derived Stem Cells","Fibro‐adipogenic Progenitors"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Affordable and clean energy"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T05:59:37.105226Z","pmid":null,"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":[]}