{"doi":"10.7554/elife.82311.sa1","title":"Decision letter: Intermittent fasting induces rapid hepatocyte proliferation to restore the hepatostat in the mouse liver","abstract":"Nutrient availability fluctuates in most natural populations, forcing organisms to undergo periods of fasting and re-feeding.It is unknown how dietary changes influence liver homeostasis.Here, we show that a switch from ad libitum feeding to intermittent fasting (IF) promotes rapid hepatocyte proliferation.Mechanistically, IF-induced hepatocyte proliferation is driven by the combined action of systemic FGF15 and localized WNT signaling.Hepatocyte proliferation during periods of fasting and re-feeding re-establishes a constant liver-to-body mass ratio, thus maintaining the hepatostat.This study provides the first example of dietary influence on adult hepatocyte proliferation and challenges the widely held view that liver tissue is mostly quiescent unless chemically or mechanically injured. Editor's evaluationThis work reports that intermittent fasting alters the homeostatic regenerative programme with fundamental implications for the use of murine models to study liver regeneration and cancer and highlights through a series of solid mechanistic studies the role of FGF/Wnt signalling interactions in modulating fasted-associated regeneration.It opens up further questions as to why this occurs, how this is beneficial to adapting to a fasting state and how we should design and interpret preclinical animal studies.","journal":null,"year":2022,"id":314206,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1013358,"name":"Tom Bird","orcid":null,"position":1,"is_corresponding":false},{"id":320556,"name":"Pramod K. Mistry","orcid":"0000-0003-3447-6421","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:33:52.047924Z","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":[]}