{"doi":"10.7554/elife.86001","title":"Sexual dimorphism in obesity is governed by RELMα regulation of adipose macrophages and eosinophils","abstract":"Obesity incidence is increasing worldwide with the urgent need to identify new therapeutics. Sex differences in immune cell activation drive obesity-mediated pathologies where males are more susceptible to obesity comorbidities and exacerbated inflammation. Here, we demonstrate that the macrophage-secreted protein RELMα critically protects females against high-fat diet (HFD)-induced obesity. Compared to male mice, serum RELMα levels were higher in both control and HFD-fed females and correlated with frequency of adipose macrophages and eosinophils. RELMα-deficient females gained more weight and had proinflammatory macrophage accumulation and eosinophil loss in the adipose stromal vascular fraction (SVF), while RELMα treatment or eosinophil transfer rescued this phenotype. Single-cell RNA-sequencing of the adipose SVF was performed and identified sex and RELMα-dependent changes. Genes involved in oxygen sensing and iron homeostasis, including hemoglobin and lncRNA Gm47283/Gm21887, correlated with increased obesity, while eosinophil chemotaxis and response to amyloid-beta were protective. Monocyte-to-macrophage transition was also dysregulated in RELMα-deficient animals. Collectively, these studies implicate a RELMα-macrophage-eosinophil axis in sex-specific protection against obesity and uncover new therapeutic targets for obesity.","journal":"eLife","year":2023,"id":330049,"datarank":0.6070698880547312,"base_score":2.833213344056216,"endowment":2.833213344056216,"self_citation_contribution":0.42498200160843247,"citation_network_contribution":0.18208788644629867,"self_endowment_contribution":0.42498200160843247,"citer_contribution":0.18208788644629867,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":10,"citers_with_citation_signal":8,"citers_with_endowment":8,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9559,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE219119"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1053269,"name":"Rebecca Elizabeth Ruggiero-Ruff","orcid":"0000-0001-9093-0233","position":1,"is_corresponding":false},{"id":1053270,"name":"Yuxin He","orcid":"0000-0002-8091-6793","position":2,"is_corresponding":false},{"id":927721,"name":"Xinru Qiu","orcid":"0000-0003-1391-252X","position":3,"is_corresponding":false},{"id":689793,"name":"Nancy M. Lainez","orcid":"0000-0002-3191-9023","position":4,"is_corresponding":false},{"id":1053271,"name":"Pedro A. Villa","orcid":"0000-0002-5245-4130","position":5,"is_corresponding":false},{"id":12333,"name":"Adam Godzik","orcid":"0000-0002-2425-852X","position":6,"is_corresponding":false},{"id":689794,"name":"Djurdjica Coss","orcid":"0000-0003-0692-1612","position":7,"is_corresponding":false},{"id":260349,"name":"Meera G. Nair","orcid":"0000-0002-1807-5161","position":8,"is_corresponding":false},{"id":1053268,"name":"Jiang Li","orcid":"0009-0008-0549-7438","position":0,"is_corresponding":true}],"reference_count":86,"raw_metadata":null,"created_at":"2026-07-19T01:09:05.843139Z","pmid":"37162190","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":[]}