{"doi":"10.1002/oby.23692","title":"<scp>Gpr75</scp>‐deficient mice are protected from high‐fat diet–induced obesity","abstract":"OBJECTIVE: G-protein coupled receptor 75 (GPR75) has been identified as the high-affinity receptor of 20-hydroxyeicosatetraenoic acid (20-HETE), a vasoactive and proinflammatory lipid, and mice overproducing 20-HETE have been shown to develop insulin resistance when fed a high-fat diet (HFD), which was prevented by a 20-HETE receptor blocker. Simultaneously, a large-scale exome sequencing of 640,000 subjects identified an association between loss-of-function GPR75 variants and protection against obesity. METHODS: Wild-type (WT) and Gpr75-deficient mice were placed on HFD for 14 weeks, and their obesity phenotype was examined. RESULTS: Male and female Gpr75 null (knockout [KO]) and heterozygous mice gained less weight than WT mice when placed on HFD. KO mice maintained the same level of energy expenditure during HFD feeding, whereas WT mice showed a significant reduction in energy expenditure. Diet-driven adiposity and adipocyte hypertrophy were greatly lessened in Gpr75-deficient mice. HFD-fed KO mice did not develop insulin resistance. Adipose tissue from Gpr75-deficient mice had increased expression of thermogenic genes and decreased levels of inflammatory markers. Moreover, insulin signaling, which was impaired in HFD-fed WT mice, was unchanged in KO mice. CONCLUSIONS: These findings suggest that GPR75 is an important player in the control of metabolism and glucose homeostasis and a likely novel therapeutic target to combat obesity-driven metabolic disorders.","journal":"Obesity","year":2023,"id":322388,"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":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9489,"is_data_producer":false,"deposit_databanks":null,"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":468244,"name":"Ankit Gilani","orcid":"0000-0002-5100-0110","position":1,"is_corresponding":false},{"id":468246,"name":"Jonathan V. Pascale","orcid":"0000-0003-2058-8625","position":2,"is_corresponding":false},{"id":827523,"name":"Elizabeth Villegas","orcid":null,"position":3,"is_corresponding":false},{"id":862378,"name":"Danielle Diegisser","orcid":null,"position":4,"is_corresponding":false},{"id":468245,"name":"Kevin Agostinucci","orcid":"0000-0002-8173-3067","position":5,"is_corresponding":false},{"id":1036564,"name":"Melissa‐Maria Kulaprathazhe","orcid":null,"position":6,"is_corresponding":false},{"id":269958,"name":"Ercument Dirice","orcid":"0000-0003-2792-7204","position":7,"is_corresponding":false},{"id":468247,"name":"Víctor García","orcid":"0000-0002-1849-8834","position":8,"is_corresponding":false},{"id":468809,"name":"Michal L. Schwartzman","orcid":null,"position":9,"is_corresponding":false},{"id":468808,"name":"Sakib Hossain","orcid":null,"position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T01:07:42.497873Z","pmid":"36854900","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":[]}