{"id":"b062ec72-5b2d-5e5f-b126-6ddba013996e","stable_key":"a8baf7e9-80e4-5d8c-adec-9a63e84d2f21:l-cysteine-fgf21-combined-restriction","predicate":"contributes_in_combined_restriction","statement":"Fgf21 knockout attenuated weight loss in mice fed a diet lacking both methionine and cysteine.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"74eddb0a-3ed4-5e11-88fc-647db79b6167","mechanism_event_label":"A stress hormone contributed under combined sulfur-amino-acid withdrawal.","subject":{"id":"8b01fe3c-a32b-5076-9c61-34d4d35e8b89","slug":"mouse-fgf21","display_name":"Mouse fibroblast growth factor 21 / Fgf21","entity_type_key":"protein"},"object":{"id":"ea7d72df-c02d-5680-907a-66c588e31392","slug":"mouse-cysteine-depletion-weight-loss","display_name":"Weight loss during systemic cysteine depletion in mice","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"74eddb0a-3ed4-5e11-88fc-647db79b6167","stable_key":"a8baf7e9-80e4-5d8c-adec-9a63e84d2f21:l-cysteine-fgf21-combined-restriction-event","event_type":"observed_relationship","label":"A stress hormone contributed under combined sulfur-amino-acid withdrawal.","description":"Fgf21 knockout attenuated weight loss in mice fed a diet lacking both methionine and cysteine.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"8b01fe3c-a32b-5076-9c61-34d4d35e8b89","slug":"mouse-fgf21","display_name":"Mouse fibroblast growth factor 21 / Fgf21","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ea7d72df-c02d-5680-907a-66c588e31392","slug":"mouse-cysteine-depletion-weight-loss","display_name":"Weight loss during systemic cysteine depletion in mice","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"ca899f13-50ad-55e5-ab99-329ae0038c74","slug":"l-cysteine","display_name":"L-Cysteine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"9d39f561-740b-5f67-bba7-8a72ef612a99","slug":"methionine","display_name":"L-Methionine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Fgf21-null versus control mice on no-methionine/no-cysteine diets; separate from the Cse-null cysteine-only experiment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Do not silently replace the combined restriction with cysteine-only restriction. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-cysteine","display_name":"L-Cysteine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"A stress hormone contributed under combined sulfur-amino-acid withdrawal.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"a1c9df09-65e2-5a79-bcf2-36b1351c4a35","evidence_kind":"source_excerpt","locator":"Lines 340-346","start_line":340,"end_line":346,"excerpt":"## l-cysteine-fgf21-combined-restriction\nA stress hormone contributed under combined sulfur-amino-acid withdrawal.\nFgf21 knockout attenuated weight loss in mice fed a diet lacking both methionine and cysteine.\nModel: Fgf21-null versus control mice on no-methionine/no-cysteine diets; separate from the Cse-null cysteine-only experiment.\nLimitations: Do not silently replace the combined restriction with cysteine-only restriction. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8\nEvidence access: Primary full text\nUnravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y","model_system":"Fgf21-null versus control mice on no-methionine/no-cysteine diets; separate from the Cse-null cysteine-only experiment.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"654560f6-8d7f-596b-8722-48d94053cfe3","stable_key":"import-a8baf7e9-80e4-5d8c-adec-9a63e84d2f21","title":"L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"f722669e54eab08ffe7289f9d79ddfc443014ed8c4bc5ba10ce2635470d22498","revision_id":"8ae25609-a031-5782-9c62-6cad8767ea46","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}