{"doi":"10.1159/000536159","title":"Diet-Stimulated Marrow Adiposity Fails to Worsen Early, Age-Related Bone Loss","abstract":"INTRODUCTION: Longitudinal effect of diet-induced obesity on bone is uncertain. Prior work showed both no effect and a decrement in bone density or quality when obesity begins prior to skeletal maturity. We aimed to quantify long-term effects of obesity on bone and bone marrow adipose tissue (BMAT) in adulthood. METHODS: Skeletally mature, female C57BL/6 mice (n = 70) aged 12 weeks were randomly allocated to low-fat diet (LFD; 10% kcal fat; n = 30) or high-fat diet (HFD; 60% kcal fat; n = 30), with analyses at 12, 15, 18, and 24 weeks (n = 10/group). Tibial microarchitecture was analyzed by µCT, and volumetric BMAT was quantified via 9.4T MRI/advanced image analysis. Histomorphometry of adipocytes and osteoclasts, and qPCR were performed. RESULTS: Body weight and visceral white adipose tissue accumulated in response to HFD started in adulthood. Trabecular bone parameters declined with advancing experimental age. BV/TV declined 22% in LFD (p = 0.0001) and 17% in HFD (p = 0.0022) by 24 weeks. HFD failed to appreciably alter BV/TV and had negligible impact on other microarchitecture parameters. Both dietary intervention and age accounted for variance in BMAT, with regional differences: distal femoral BMAT was more responsive to diet, while proximal femoral BMAT was more attenuated by age. BMAT increased 60% in the distal metaphysis in HFD at 18 and 24 weeks (p = 0.0011). BMAT in the proximal femoral diaphysis, unchanged by diet, decreased 45% due to age (p = 0.0002). Marrow adipocyte size via histomorphometry supported MRI quantification. Osteoclast number did not differ between groups. Tibial qPCR showed attenuation of some adipose, metabolism, and bone genes. A regulator of fatty acid β-oxidation, cytochrome C (CYCS), was 500% more abundant in HFD bone (p < 0.0001; diet effect). CYCS also increased due to age, but to a lesser extent. HFD mildly increased OCN, TRAP, and SOST. CONCLUSIONS: Long-term high fat feeding after skeletal maturity, despite upregulation of visceral adiposity, body weight, and BMAT, failed to attenuate bone microarchitecture. In adulthood, we found aging to be a more potent regulator of microarchitecture than diet-induced obesity.","journal":"Obesity Facts","year":2024,"id":455165,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9609,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":700474,"name":"Sarah E Little","orcid":"0000-0001-5818-9676","position":1,"is_corresponding":false},{"id":474949,"name":"Gabriel M. Pagnotti","orcid":"0000-0003-0888-5117","position":2,"is_corresponding":false},{"id":348008,"name":"Buer Sen","orcid":"0000-0002-0487-7817","position":3,"is_corresponding":false},{"id":1278998,"name":"Zhihui Xie","orcid":"0000-0003-4699-5093","position":4,"is_corresponding":false},{"id":348011,"name":"Gunes Uzer","orcid":"0000-0002-1178-4942","position":5,"is_corresponding":false},{"id":1279423,"name":"Guniz Bas Uzer","orcid":null,"position":6,"is_corresponding":false},{"id":356611,"name":"Xiaopeng Zong","orcid":"0000-0003-4235-6948","position":7,"is_corresponding":false},{"id":266786,"name":"Martin Styner","orcid":"0000-0002-8747-5118","position":8,"is_corresponding":false},{"id":348014,"name":"Janet Rubin","orcid":"0000-0003-3534-8667","position":9,"is_corresponding":false},{"id":348012,"name":"Maya Styner","orcid":"0000-0001-9790-8645","position":10,"is_corresponding":false},{"id":700475,"name":"Cody McGrath","orcid":"0000-0003-0176-4240","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":null,"created_at":"2026-07-19T02:03:17.458329Z","pmid":"38224679","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":[]}