{"doi":"10.1172/jci.insight.174164","title":"Intestinal FGF15 regulates bile acid and cholesterol metabolism but not glucose and energy balance","abstract":"Fibroblast growth factor 15/19 (FGF15/19, mouse/human ortholog) is expressed in the ileal enterocytes of the small intestine and released postprandially in response to bile acid absorption. Previous reports of FGF15-/- mice have limited our understanding of gut-specific FGF15's role in metabolism. Therefore, we studied the role of endogenous gut-derived FGF15 in bile acid, cholesterol, glucose, and energy balance. We found that circulating levels of FGF19 were reduced in individuals with obesity and comorbidities, such as type 2 diabetes and metabolic dysfunction-associated fatty liver disease. Gene expression analysis of ileal FGF15-positive cells revealed differential expression during the obesogenic state. We fed standard chow or a high-fat metabolic dysfunction-associated steatohepatitis-inducing diet to control and intestine-derived FGF15-knockout (FGF15INT-KO) mice. Control and FGF15INT-KO mice gained similar body weight and adiposity and did not show genotype-specific differences in glucose, mixed meal, pyruvate, and glycerol tolerance. FGF15INT-KO mice had increased systemic bile acid levels but decreased cholesterol levels, pointing to a primary role for gut-derived FGF15 in regulating bile acid and cholesterol metabolism when exposed to obesogenic diet. These studies show that intestinal FGF15 plays a specific role in bile acid and cholesterol metabolism regulation but is not essential for energy and glucose balance.","journal":"JCI Insight","year":2024,"id":423697,"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":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"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":132718,"name":"Jae Hoon Shin","orcid":null,"position":1,"is_corresponding":false},{"id":277956,"name":"Ziru Li","orcid":"0000-0002-2755-9299","position":2,"is_corresponding":false},{"id":307435,"name":"Alan C. Rupp","orcid":"0000-0001-5363-4494","position":3,"is_corresponding":false},{"id":1219453,"name":"Nicole Miller","orcid":"0000-0003-3446-3911","position":4,"is_corresponding":false},{"id":281133,"name":"Stace Kernodle","orcid":"0000-0001-7750-8804","position":5,"is_corresponding":false},{"id":899637,"name":"Nicolas Lanthier","orcid":"0000-0002-7651-9314","position":6,"is_corresponding":false},{"id":1219454,"name":"Paulina Henry","orcid":"0000-0002-6273-7775","position":7,"is_corresponding":false},{"id":1220027,"name":"Nikhil Seshadri","orcid":null,"position":8,"is_corresponding":false},{"id":517368,"name":"Andriy Myronovych","orcid":"0000-0003-1361-0644","position":9,"is_corresponding":false},{"id":247003,"name":"Ormond A. MacDougald","orcid":"0000-0001-6907-7960","position":10,"is_corresponding":false},{"id":319905,"name":"Robert W. O’Rourke","orcid":"0000-0002-4038-4198","position":11,"is_corresponding":false},{"id":277478,"name":"Rohit Kohli","orcid":"0000-0002-0198-7703","position":12,"is_corresponding":false},{"id":246590,"name":"Charles Burant","orcid":"0000-0001-9189-5003","position":13,"is_corresponding":false},{"id":502534,"name":"Amy E. Rothberg","orcid":"0000-0002-0243-9135","position":14,"is_corresponding":false},{"id":107074,"name":"Randy J. Seeley","orcid":"0000-0002-3721-5625","position":15,"is_corresponding":false},{"id":307432,"name":"Nadejda Bozadjieva-Kramer","orcid":"0000-0001-9796-2916","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T01:58:01.889748Z","pmid":"38587078","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":[]}