{"doi":"10.1002/oby.24221","title":"Metabolically unhealthy adipose tissue is characterized by reductions in mitochondrial size and function","abstract":"OBJECTIVE: Adipose function, not mass, underpins metabolic health. Lean and obese nonhuman primates (NHPs) naturally develop metabolic syndrome. Mitochondria-related measures in subcutaneous adipose tissue (SQ AT) and peripheral blood mononuclear cells may elucidate differences that transcend adiposity measures. METHODS: Obesity statuses ranged from very lean to severely obese (<9%->50%, n = 44), which were equivalent in healthy or unhealthy NHPs (metabolic syndrome score difference, p < 0.001). We evaluated SQ AT histology, electron microscopy, tissue proteins, and bioenergetics. RESULTS: Unhealthy adipocytes had mitochondria one-half the size of healthy adipocytes (p < 0.01), whereas adipocyte cell sizes were comparable. Consistent with small mitochondria, we saw deficiencies in mitochondrial fusion and quality-control proteins in SQ AT from unhealthy NHPs (all p < 0.05). Smaller mitochondria in unhealthy adipocytes were consistent with low SQ AT tissue respiration (p < 0.05). Mitochondrial size was specifically reduced with unhealthiness, as mitochondrial abundance, size, and related metrics were unrelated to adiposity. Isolated stromal vascular cells showed comparable respirometry profiles, substantiating specificity of adipocyte-related mitochondrial defects. Peripheral blood mononuclear cell bioenergetic indices were increased in unhealthy NHPs, indicative of immune cell activation, and correlated to SQ AT inflammatory cytokines. CONCLUSIONS: We conclude that targeting mitochondrial fusion processes would be a rational strategy to improve metabolic health, independent of total fat mass.","journal":"Obesity","year":2025,"id":551659,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.5324,"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":1027282,"name":"Masha Long","orcid":null,"position":1,"is_corresponding":false},{"id":936620,"name":"Abigail G. Williams","orcid":null,"position":2,"is_corresponding":false},{"id":1448014,"name":"McKinley Santiago","orcid":null,"position":3,"is_corresponding":false},{"id":1448015,"name":"J Tonkin","orcid":null,"position":4,"is_corresponding":false},{"id":505285,"name":"Christina Stevens","orcid":"0009-0005-9771-9007","position":5,"is_corresponding":false},{"id":379205,"name":"Matthew A. Davis","orcid":"0000-0001-6544-0451","position":6,"is_corresponding":false},{"id":380609,"name":"Alistaire D. Ruggiero","orcid":"0000-0002-1942-2751","position":7,"is_corresponding":false},{"id":233451,"name":"Darren C. Henstridge","orcid":"0000-0003-4988-767X","position":8,"is_corresponding":false},{"id":1447733,"name":"Dino Premilovac","orcid":"0000-0003-2770-4713","position":9,"is_corresponding":false},{"id":237685,"name":"Kylie Kavanagh","orcid":"0000-0001-8772-6186","position":10,"is_corresponding":false},{"id":936618,"name":"Darla DeStephanis","orcid":null,"position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T02:54:29.318076Z","pmid":"39948771","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":[]}