{"id":"d5a30d08-932c-5ff5-bdbe-4d038da0d9fe","stable_key":"dc8975b1-95ff-5d9b-be17-a1c04610cca7:mo-marc-ko-protection-2026","predicate":"loss_reduces","statement":"Global and liver-specific Mtarc1 knockout protected against diet-induced triglyceride accumulation, inflammation and fibrosis.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"487151fe-120d-5676-bc58-69ff05cc00fc","mechanism_event_label":"This study also found protection after targeted MTARC1 loss.","subject":{"id":"9a4caa98-09a8-5d90-a55a-40de766b54e1","slug":"mouse-mtarc1","display_name":"Mouse mitochondrial amidoxime-reducing component 1 / Mtarc1","entity_type_key":"protein"},"object":{"id":"688a914a-e1d2-5f5d-8b13-2884642f58f0","slug":"hepatic-triglyceride-accumulation","display_name":"Hepatic triglyceride accumulation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"487151fe-120d-5676-bc58-69ff05cc00fc","stable_key":"dc8975b1-95ff-5d9b-be17-a1c04610cca7:mo-marc-ko-protection-2026-event","event_type":"biochemical_relationship","label":"This study also found protection after targeted MTARC1 loss.","description":"Global and liver-specific Mtarc1 knockout protected against diet-induced triglyceride accumulation, inflammation and fibrosis.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3674b224-cb1f-559e-8967-c30efae9e2a7","slug":"hepatic-fibrosis","display_name":"Hepatic fibrosis","entity_type_key":"cellular_process"},"role":"reduced outcome","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9a4caa98-09a8-5d90-a55a-40de766b54e1","slug":"mouse-mtarc1","display_name":"Mouse mitochondrial amidoxime-reducing component 1 / Mtarc1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"688a914a-e1d2-5f5d-8b13-2884642f58f0","slug":"hepatic-triglyceride-accumulation","display_name":"Hepatic triglyceride accumulation","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/molybdenum-research/41641916.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"52b4d4d00867faaa1bb51ff6055f887a72c4c0d266bf7a1665b3780ce03aee64\", \"start_char\": 0, \"end_char\": 1681, \"text_sha256\": \"52b4d4d00867faaa1bb51ff6055f887a72c4c0d266bf7a1665b3780ce03aee64\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Global/liver Mtarc1 knockout with Pnpla2, Lipa, Pemt and Cept1 interventions","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Diet-induced liver disease with gene knockouts/knockdowns and multi-omics","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Preclinical mechanism; no evidence that dietary molybdenum restriction selectively reproduces MTARC1 targeting.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Molybdenum research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"molybdenum","display_name":"Molybdenum","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Mus musculus; supporting cell studies","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"This study also found protection after targeted MTARC1 loss.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mo-p41641916] MTARC1 Inactivation Remodels Lipid Droplets to Protect Against Metabolic Fatty Liver Disease. (2026). https://pubmed.ncbi.nlm.nih.gov/41641916/ DOI: 10.1111/liv.70539","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Hepatic lipid droplets","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"5a82241d-c48e-5bec-87f0-59bd8fc60835","evidence_kind":"source_excerpt","locator":"Lines 1548-1559","start_line":1548,"end_line":1559,"excerpt":"### mo-marc-ko-protection-2026\nGlobal and liver-specific Mtarc1 knockout protected against diet-induced triglyceride accumulation, inflammation and fibrosis.\nCondition category: machinery_impairment\nnutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This study also found protection after targeted MTARC1 loss.\norganism: Mus musculus; supporting cell studies\ntissue_or_cell_type: Hepatic lipid droplets\nexperimental_model: Global/liver Mtarc1 knockout with Pnpla2, Lipa, Pemt and Cept1 interventions\nlimitations: Preclinical mechanism; no evidence that dietary molybdenum restriction selectively reproduces MTARC1 targeting.\nexposure: Diet-induced liver disease with gene knockouts/knockdowns and multi-omics\nevidence_span: {\"source_cache\": \"artifacts/molybdenum-research/41641916.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"52b4d4d00867faaa1bb51ff6055f887a72c4c0d266bf7a1665b3780ce03aee64\", \"start_char\": 0, \"end_char\": 1681, \"text_sha256\": \"52b4d4d00867faaa1bb51ff6055f887a72c4c0d266bf7a1665b3780ce03aee64\"}\n[mo-p41641916] MTARC1 Inactivation Remodels Lipid Droplets to Protect Against Metabolic Fatty Liver Disease. (2026). https://pubmed.ncbi.nlm.nih.gov/41641916/ DOI: 10.1111/liv.70539","model_system":"Global/liver Mtarc1 knockout with Pnpla2, Lipa, Pemt and Cept1 interventions","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [mo-p41641916] MTARC1 Inactivation Remodels Lipid Droplets to Protect Against Metabolic Fatty Liver Disease. (2026). https://pubmed.ncbi.nlm.nih.gov/41641916/ DOI: 10.1111/liv.70539","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"1aa6da60-8284-5252-8dd9-ac2250d5ced5","stable_key":"import-dc8975b1-95ff-5d9b-be17-a1c04610cca7","title":"Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"143147eb9ac7fe750bdd33bb50d7773bc0cd49cc94faf219aebce3c3d760dd8f","revision_id":"90c2239d-290b-5e16-815a-f94d30569ebd","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"d317ce32-5312-5194-b721-e8311efb2f34","title":"MTARC1 knockout: conflicting liver-protection results in mice","kind":"contradiction","status":"open","why":"A 2024 whole-body knockout study reported no protection against triglyceride accumulation, inflammation or fibrosis; 2025 and 2026 studies reported protection after global deletion and liver-directed interventions. Genetic background, diet, disease induction, timing, sex and Marc2 contribution are candidate explanations that require direct comparison. The A168T knock-in is a different perturbation and is retained as context rather than labeled the same experiment.","resolution":"Unresolved published disagreement. Preserve each model and outcome. Discuss testable mechanisms including paralog contribution and lipid-droplet turnover; do not treat any explanation as established or recommend molybdenum depletion from targeted gene-loss results.","created_at":"2026-09-17 17:12:18","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/d317ce32-5312-5194-b721-e8311efb2f34","sides":[{"conflict_id":"d317ce32-5312-5194-b721-e8311efb2f34","ordinal":0,"label":"Removing MTARC1 did not help in this experiment.","revision_id":"90c2239d-290b-5e16-815a-f94d30569ebd","start_line":1509,"end_line":1520,"quote":"### mo-marc-ko-null\nWhole-body Marc1 knockout did not protect against hepatic triglyceride accumulation, inflammation or fibrosis in this mouse study.\nCondition category: machinery_impairment\nnutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Removing MTARC1 did not help in this experiment.\norganism: Human genetics in about 540000 individuals; Mus musculus knockout\ntissue_or_cell_type: Liver phenotypes\nexperimental_model: Multi-ancestry exome association, human protein studies and whole-body mouse Marc1 knockout\nlimitations: Human association and mouse intervention are separate. The knockout null result differs from later published mouse knockout protection.\nexposure: MARC1 variants and mouse global knockout\nevidence_span: {\"source_cache\": \"artifacts/molybdenum-research/38437227.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"152bcc386bca67c8cd4891d284098784ebbdbf9c507f713f96b996bb3c75bd1b\", \"start_char\": 0, \"end_char\": 1333, \"text_sha256\": \"152bcc386bca67c8cd4891d284098784ebbdbf9c507f713f96b996bb3c75bd1b\"}\n[mo-p38437227] Divergent role of Mitochondrial Amidoxime Reducing Component 1 (MARC1) in human and mouse. (2024). https://pubmed.ncbi.nlm.nih.gov/38437227/ DOI: 10.1371/journal.pgen.1011179","source_key":"import-dc8975b1-95ff-5d9b-be17-a1c04610cca7","source_title":"Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17)","claim_ids":["470a75b0-36f7-5e4f-bb9c-74b4d8a659b2"]},{"conflict_id":"d317ce32-5312-5194-b721-e8311efb2f34","ordinal":1,"label":"Removing MTARC1 helped in these experiments.","revision_id":"90c2239d-290b-5e16-815a-f94d30569ebd","start_line":1535,"end_line":1546,"quote":"### mo-marc-ko-protection-2025\nGlobal deletion and hepatocyte-specific knockdown of Mtarc1 reduced steatosis and fibrosis in multiple mouse models.\nCondition category: machinery_impairment\nnutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Removing MTARC1 helped in these experiments.\norganism: Mus musculus; human variant cell experiments\ntissue_or_cell_type: Liver and hepatocytes\nexperimental_model: Global deletion and hepatocyte-specific knockdown across mouse MASH/fibrosis models; cellular variants\nlimitations: Preclinical protein-targeting study. A165T retained mitochondrial localization in these experiments, unlike the endogenous HepG2 study; construct/model effects remain unresolved.\nexposure: Mtarc1 depletion under lipotoxic and diet/fibrosis challenges\nevidence_span: {\"source_cache\": \"artifacts/molybdenum-research/39927988.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"0ac1fb695999e1691580706469d581ce6bd90eeab03f7c26c1c79fbb4b4e169d\", \"start_char\": 0, \"end_char\": 1938, \"text_sha256\": \"0ac1fb695999e1691580706469d581ce6bd90eeab03f7c26c1c79fbb4b4e169d\"}\n[mo-p39927988] Loss of mitochondrial amidoxime-reducing component 1 (mARC1) prevents disease progression by reducing fibrosis in multiple mouse models of chronic liver disease. (2025). https://pubmed.ncbi.nlm.nih.gov/39927988/ DOI: 10.1097/hc9.0000000000000637","source_key":"import-dc8975b1-95ff-5d9b-be17-a1c04610cca7","source_title":"Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17)","claim_ids":["67304e17-355c-505b-8e6d-7ee52a22f823"]},{"conflict_id":"d317ce32-5312-5194-b721-e8311efb2f34","ordinal":2,"label":"This study also found protection after targeted MTARC1 loss.","revision_id":"90c2239d-290b-5e16-815a-f94d30569ebd","start_line":1548,"end_line":1559,"quote":"### mo-marc-ko-protection-2026\nGlobal and liver-specific Mtarc1 knockout protected against diet-induced triglyceride accumulation, inflammation and fibrosis.\nCondition category: machinery_impairment\nnutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This study also found protection after targeted MTARC1 loss.\norganism: Mus musculus; supporting cell studies\ntissue_or_cell_type: Hepatic lipid droplets\nexperimental_model: Global/liver Mtarc1 knockout with Pnpla2, Lipa, Pemt and Cept1 interventions\nlimitations: Preclinical mechanism; no evidence that dietary molybdenum restriction selectively reproduces MTARC1 targeting.\nexposure: Diet-induced liver disease with gene knockouts/knockdowns and multi-omics\nevidence_span: {\"source_cache\": \"artifacts/molybdenum-research/41641916.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"52b4d4d00867faaa1bb51ff6055f887a72c4c0d266bf7a1665b3780ce03aee64\", \"start_char\": 0, \"end_char\": 1681, \"text_sha256\": \"52b4d4d00867faaa1bb51ff6055f887a72c4c0d266bf7a1665b3780ce03aee64\"}\n[mo-p41641916] MTARC1 Inactivation Remodels Lipid Droplets to Protect Against Metabolic Fatty Liver Disease. (2026). https://pubmed.ncbi.nlm.nih.gov/41641916/ DOI: 10.1111/liv.70539","source_key":"import-dc8975b1-95ff-5d9b-be17-a1c04610cca7","source_title":"Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17)","claim_ids":["d5a30d08-932c-5ff5-bdbe-4d038da0d9fe"]}]}],"corrections":[],"research":null}