{"doi":"10.1210/jendso/bvaf134","title":"Adipose Tissue Estrogen Receptor-Alpha Overexpression Ameliorates High-Fat Diet–Induced Adipose Tissue Inflammation","abstract":"Context: We created an innovative mouse model that enables inducible overexpression of estrogen receptor-alpha (ERα), specifically in adipose tissue (Adipo-ERα↑). Objective: We aimed to investigate how elevated Adipo-ERα↑ influences the development of high-fat diet (HFD)-induced obesity in both male and female mice. Methods: Male and female Adipo-ERα↑ mice and littermate controls were fed a low-fat diet (LFD) or HFD for 13 weeks. Adipo-ERα↑ was induced at the initiation of dietary treatment. Body morphology and composition, hepatic lipid accumulation, glucose tolerance, fasting insulin concentrations, and adipose tissue mRNA profiling were assessed. Liquid chromatography-mass spectrometry was used to determine circulating and adipose tissue sex steroid content. Results: Adipo-ERα↑ significantly reduced adiposity and hepatic lipid accumulation in HFD-fed female mice but not in male mice. However, in both sexes, Adipo-ERα↑ greatly reduced adipose tissue inflammation characteristic of obesity. Despite these effects, Adipo-ERα↑ did not improve glucose tolerance or fasting insulin levels and did not affect circulating and adipose tissue sex steroid content. Conclusion: Adipo-ERα↑ elicits distinct sex-specific effects with respect to body composition and hepatic lipid accumulation, which are likely driven by variations in circulating and tissue estrogen levels. Nonetheless, despite differences in estrogen levels, Adipo-ERα↑ profoundly reduced obesity-linked adipose tissue inflammation in both sexes, providing further evidence that therapeutically targeting ERα may be beneficial for treating obesity-associated inflammation.","journal":"Journal of the Endocrine Society","year":2025,"id":520022,"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":0.949,"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":706606,"name":"Christian Unger","orcid":"0000-0002-4216-3575","position":1,"is_corresponding":false},{"id":1310797,"name":"M Chase Kettering","orcid":null,"position":2,"is_corresponding":false},{"id":1054392,"name":"Cassidy E Socia","orcid":null,"position":3,"is_corresponding":false},{"id":706605,"name":"Ahmed Al-Adhami","orcid":"0000-0002-9072-551X","position":4,"is_corresponding":false},{"id":1054393,"name":"Barton C Rice","orcid":null,"position":5,"is_corresponding":false},{"id":1310798,"name":"Darya S Niamira","orcid":null,"position":6,"is_corresponding":false},{"id":1389624,"name":"Ben P Wiznitzer","orcid":null,"position":7,"is_corresponding":false},{"id":396952,"name":"Diego Altomare","orcid":"0000-0002-9126-5703","position":8,"is_corresponding":false},{"id":578254,"name":"William E. Cotham","orcid":null,"position":9,"is_corresponding":false},{"id":407577,"name":"Reilly T. Enos","orcid":"0000-0001-5571-4586","position":10,"is_corresponding":false},{"id":706608,"name":"Marion C Hope","orcid":"0000-0002-4855-5764","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T02:49:23.618703Z","pmid":"40980540","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":[]}