{"doi":"10.1101/2020.01.10.902346","title":"Bariatric surgery reveals a gut-restricted TGR5 agonist that exhibits anti-diabetic effects","abstract":"Abstract Bariatric surgery, the most effective treatment for obesity and type 2 diabetes, is consistently associated with increased levels of the incretin hormone GLP-1 and changes in overall levels of circulating bile acids. The levels of individual bile acids in the GI tract following surgery, however, have remained largely unstudied. Using UPLC-MS-based quantification, we observed an increase in an endogenous bile acid, cholic acid-7-sulfate (CA7S), in the GI tract of both mice and humans after sleeve gastrectomy. We show that CA7S is a TGR5 agonist that induces GLP-1 secretion in vitro and in vivo and that CA7S administration increases glucose tolerance in insulin-resistant mice in a GLP-1 receptor-dependent manner. CA7S remains gut-restricted, minimizing off-target effects previously observed for TGR5 agonists absorbed into circulation. By studying changes in individual metabolites following surgery, this study has revealed a naturally occurring TGR5 agonist that exerts systemic glucoregulatory effects while remaining confined to the gut.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":124542,"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":2,"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":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":569198,"name":"David A. Harris","orcid":"0000-0001-5588-1632","position":1,"is_corresponding":false},{"id":456192,"name":"Hassan Aliakbarian","orcid":"0000-0001-9965-6920","position":2,"is_corresponding":false},{"id":257771,"name":"Matthew T. Henke","orcid":"0000-0001-8325-6420","position":3,"is_corresponding":false},{"id":569656,"name":"Renuka Subramaniam","orcid":null,"position":4,"is_corresponding":false},{"id":504192,"name":"Ashley H. Vernon","orcid":null,"position":5,"is_corresponding":false},{"id":456194,"name":"Ali Tavakkoli","orcid":"0000-0002-7430-1848","position":6,"is_corresponding":false},{"id":569199,"name":"Eric G. Sheu","orcid":"0000-0003-2707-1768","position":7,"is_corresponding":false},{"id":44568,"name":"A. Sloan Devlin","orcid":"0000-0001-5598-3751","position":8,"is_corresponding":false},{"id":569197,"name":"Snehal N. Chaudhari","orcid":"0000-0003-4389-3366","position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-18T23:15:07.789881Z","pmid":null,"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":[]}