{"doi":"10.1016/j.apsb.2024.11.022","title":"Intestinal stearoyl-coenzyme A desaturase-inhibition improves obesity-associated metabolic disorders","abstract":"Stearoyl-coenzyme A desaturase 1 (SCD1) catalyzes the rate-limiting step of de novo lipogenesis and modulates lipid homeostasis. Although numerous SCD1 inhibitors were tested for treating metabolic disorders both in preclinical and clinic studies, the tissue-specific roles of SCD1 in modulating obesity-associated metabolic disorders and determining the pharmacological effect of chemical SCD1 inhibition remain unclear. Here a novel role for intestinal SCD1 in obesity-associated metabolic disorders was uncovered. Intestinal SCD1 was found to be induced during obesity progression both in humans and mice. Intestine-specific, but not liver-specific, SCD1 deficiency reduced obesity and hepatic steatosis. A939572, an SCD1-specific inhibitor, ameliorated obesity and hepatic steatosis dependent on intestinal, but not hepatic, SCD1. Mechanistically, intestinal SCD1 deficiency impeded obesity-induced oxidative stress through its novel function of inducing metallothionein 1 in intestinal epithelial cells. These results suggest that intestinal SCD1 could be a viable target that underlies the pharmacological effect of chemical SCD1 inhibition in the treatment of obesity-associated metabolic disorders. Scd1 gene knockout and pharmacological inhibition of SCD1 in intestine promote obesity by inducing MT1 in intestinal epithelial cells that impedes obesity-induced oxidative stress.","journal":"Acta Pharmaceutica Sinica B","year":2024,"id":456865,"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":0.9509,"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":1281711,"name":"Yang Zhang","orcid":"0000-0002-9081-0802","position":1,"is_corresponding":false},{"id":1281712,"name":"Zhipeng Zhang","orcid":"0000-0002-5346-3055","position":2,"is_corresponding":false},{"id":678643,"name":"Nana Yan","orcid":"0000-0002-6418-3139","position":3,"is_corresponding":false},{"id":1064636,"name":"Vorthon Sawaswong","orcid":"0000-0003-2805-6690","position":4,"is_corresponding":false},{"id":631059,"name":"Lulu Sun","orcid":"0000-0001-8876-5099","position":5,"is_corresponding":false},{"id":1282227,"name":"Wanwan Guo","orcid":null,"position":6,"is_corresponding":false},{"id":570261,"name":"Ping Wang","orcid":"0000-0002-7189-9418","position":7,"is_corresponding":false},{"id":287998,"name":"Kristopher W. Krausz","orcid":"0000-0003-2910-7787","position":8,"is_corresponding":false},{"id":251345,"name":"Oksana Gavrilova","orcid":"0000-0002-9310-1198","position":9,"is_corresponding":false},{"id":257521,"name":"James M. Ntambi","orcid":"0000-0001-9784-9550","position":10,"is_corresponding":false},{"id":678645,"name":"Haiping Hao","orcid":"0000-0003-2522-7546","position":11,"is_corresponding":false},{"id":1281713,"name":"Tingting Yan","orcid":"0000-0002-2368-9248","position":12,"is_corresponding":false},{"id":281044,"name":"Frank J. Gonzalez","orcid":"0000-0002-7990-2140","position":13,"is_corresponding":false},{"id":399429,"name":"Yangliu Xia","orcid":"0000-0002-5742-7182","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T02:03:32.516678Z","pmid":"40177566","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":[]}