{"doi":"10.1083/jcb.202305093","title":"Calorie restriction activates a gastric Notch-FOXO1 pathway to expand ghrelin cells","abstract":"Calorie restriction increases lifespan. Among the tissue-specific protective effects of calorie restriction, the impact on the gastrointestinal tract remains unclear. We report increased numbers of chromogranin A-positive (+), including orexigenic ghrelin+ cells, in the stomach of calorie-restricted mice. This effect was accompanied by increased Notch target Hes1 and Notch ligand Jag1 and was reversed by blocking Notch with DAPT, a gamma-secretase inhibitor. Primary cultures and genetically modified reporter mice show that increased endocrine cell abundance is due to altered Lgr5+ stem and Neurog3+ endocrine progenitor cell proliferation. Different from the intestine, calorie restriction decreased gastric Lgr5+ stem cells, while increasing a FOXO1/Neurog3+ subpopulation of endocrine progenitors in a Notch-dependent manner. Further, activation of FOXO1 was sufficient to promote endocrine cell differentiation independent of Notch. The Notch inhibitor PF-03084014 or ghrelin receptor antagonist GHRP-6 reversed the phenotypic effects of calorie restriction in mice. Tirzepatide additionally expanded ghrelin+ cells in mice. In summary, calorie restriction promotes Notch-dependent, FOXO1-regulated gastric endocrine cell differentiation.","journal":"The Journal of Cell Biology","year":2024,"id":461110,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.951,"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":1289651,"name":"Sophia Spiegel","orcid":"0009-0008-9116-7506","position":1,"is_corresponding":false},{"id":703345,"name":"Maria Mukhanova","orcid":"0000-0003-4928-3294","position":2,"is_corresponding":false},{"id":254356,"name":"Michael J. Kraakman","orcid":"0000-0002-5755-0447","position":3,"is_corresponding":false},{"id":458942,"name":"Wen Du","orcid":"0000-0002-8138-774X","position":4,"is_corresponding":false},{"id":458945,"name":"Takumi Kitamoto","orcid":"0000-0002-9457-267X","position":5,"is_corresponding":false},{"id":444991,"name":"Junjie Yu","orcid":"0000-0001-5603-6094","position":6,"is_corresponding":false},{"id":1289652,"name":"Zhaobin Deng","orcid":"0009-0009-4278-8178","position":7,"is_corresponding":false},{"id":109694,"name":"Utpal B. Pajvani","orcid":"0000-0001-5991-2723","position":8,"is_corresponding":false},{"id":104004,"name":"Domenico Accili","orcid":"0000-0002-6874-3949","position":9,"is_corresponding":false},{"id":774774,"name":"Wendy M. McKimpson","orcid":"0000-0002-2262-5998","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T02:04:12.271488Z","pmid":"38958606","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":[]}