{"doi":"10.1002/jcsm.70027","title":"High‐Calorie Diet During Pregnancy Leads to Muscular Fibrosis and Neuromuscular Damage in Offspring Mice","abstract":"ABSTRACT Background Sarcopenia, recognized as an age‐related loss of muscle mass and function, is a critical risk for geriatric health. We previously demonstrated that maternal high‐fat diet (HFD) suppresses mitochondrial biogenesis during fetal skeletal muscle development, but the longitudinal effect of maternal HFD challenge on offspring muscle sarcopenia and fitness impairment remains unclear. Mitochondrial polymerase γ (PolG) mutation accelerates mitochondrial DNA mutations and leads to premature aging. Methods To determine the mechanisms underlying the longitudinal effect of maternal HFD challenge on offspring sarcopenia and aging, heterozygote mitochondrial polymerase γ mutated ( PolgA mut/+ ) female mice were fed either a control diet (CD) or HFD during pregnancy, which were mated with heterozygote PolgA male mice. Thus, we had four experimental groups: maternal CD (M‐CD) + WT, M‐CD + PolgA mut , M‐HFD + WT and M‐HFD + PolgA mut . Six‐month‐old offspring mice were utilized for testing metabolic health, maximal muscle strength and cardiorespiratory fitness capacity. Then, 9‐month‐old offspring mice were used for biochemical and histochemical analyses. Results Maternal high‐calorie diet during pregnancy decreased offspring muscle strength and cardiorespiratory function ( p < 0.05), which were associated with loss of muscle mass ( p < 0.05). These adverse outcomes were most dramatic in M‐HFD with PolG mutation ( p < 0.05). Maternal HFD challenge activated muscle atrophy signalling, including MuRF1 and Atrogin‐1 ( p < 0.05), which were worsened in PolgA mice ( p < 0.05). Furthermore, M‐HFD increased the accumulation of intramuscular fibrosis in PolgA offspring ( p < 0.05). In addition, M‐HFD increased the risk of neuromuscular damage by attenuating GABA A receptor pathway in PolgA mice ( p < 0.05). Conclusions Maternal high‐calorie diet during pregnancy induced offspring muscle atrophy and intramuscular fibrosis, especially with PolG mutation, underscoring mitochondrial dysfunction in linking maternal HFD to offspring premature aging.","journal":"Journal of Cachexia Sarcopenia and Muscle","year":2025,"id":534716,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9639,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":287100,"name":"Song Ah Chae","orcid":null,"position":1,"is_corresponding":false},{"id":1418377,"name":"Yun Chun","orcid":null,"position":2,"is_corresponding":false},{"id":1417847,"name":"Hongyang Wang","orcid":"0000-0003-2858-8478","position":3,"is_corresponding":false},{"id":138844,"name":"Zhihua Jiang","orcid":null,"position":4,"is_corresponding":false},{"id":285293,"name":"‬Min Du","orcid":"0000-0002-7232-072X","position":5,"is_corresponding":false},{"id":285286,"name":"Jun Seok Son","orcid":"0000-0001-6807-993X","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-19T02:51:52.019261Z","pmid":"40957424","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":[]}