{"doi":"10.1073/pnas.1908137116","title":"Targeting liver aldehyde dehydrogenase-2 prevents heavy but not moderate alcohol drinking","abstract":"<jats:title>Significance</jats:title>\n                  <jats:p>\n                    It is generally accepted that ethanol and its metabolite acetaldehyde are primarily metabolized in the liver via the alcohol dehydrogenase and the aldehyde dehydrogenase-2 (ALDH2), respectively. However, by using tissue-specific\n                    <jats:italic>Aldh2</jats:italic>\n                    knockout mice, we demonstrated that the liver ALDH2 is only responsible for approximately half of circulating acetaldehyde clearance after acute alcohol intake. Thus, cumulative ALDH2 activity from multiple organs may contribute to circulating acetaldehyde clearance. The present study shows that, although the liver ALDH2 only partially contributes to acetaldehyde clearance, genetic deletion or knockdown of the liver\n                    <jats:italic>Aldh2</jats:italic>\n                    decreases excessive but not light to moderate alcohol drinking. Our results suggest that liver-specific ALDH2 inhibition may be an effective strategy for the treatment of alcohol user disorder with excessive drinking.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2019,"id":595557,"datarank":0.637274286307404,"base_score":4.248495242049359,"endowment":4.248495242049359,"self_citation_contribution":0.637274286307404,"citation_network_contribution":0.0,"self_endowment_contribution":0.637274286307404,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":69,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1284758,"name":"Tianyi Ren","orcid":"0000-0001-9548-6645","position":1,"is_corresponding":false},{"id":1075739,"name":"Tony Jourdan","orcid":"0000-0001-7955-8127","position":2,"is_corresponding":false},{"id":333449,"name":"Robert J. Pawlosky","orcid":"0009-0008-3075-7481","position":3,"is_corresponding":false},{"id":1248715,"name":"Elaine Han","orcid":"0000-0003-1694-1908","position":4,"is_corresponding":false},{"id":833769,"name":"Seung-Jin Kim","orcid":"0000-0001-7470-7293","position":5,"is_corresponding":false},{"id":350718,"name":"Li Zhang","orcid":"0000-0003-1489-0879","position":6,"is_corresponding":false},{"id":176717,"name":"George F. Koob","orcid":null,"position":7,"is_corresponding":false},{"id":239667,"name":"Bin Gao","orcid":"0000-0003-2282-015X","position":8,"is_corresponding":false},{"id":544,"name":"Adrien Guillot","orcid":"0000-0002-6002-9986","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Targeting liver aldehyde dehydrogenase-2 prevents heavy but not moderate alcohol drinking","abstract":"<jats:title>Significance</jats:title>\n                  <jats:p>\n                    It is generally accepted that ethanol and its metabolite acetaldehyde are primarily metabolized in the liver via the alcohol dehydrogenase and the aldehyde dehydrogenase-2 (ALDH2), respectively. However, by using tissue-specific\n                    <jats:italic>Aldh2</jats:italic>\n                    knockout mice, we demonstrated that the liver ALDH2 is only responsible for approximately half of circulating acetaldehyde clearance after acute alcohol intake. Thus, cumulative ALDH2 activity from multiple organs may contribute to circulating acetaldehyde clearance. The present study shows that, although the liver ALDH2 only partially contributes to acetaldehyde clearance, genetic deletion or knockdown of the liver\n                    <jats:italic>Aldh2</jats:italic>\n                    decreases excessive but not light to moderate alcohol drinking. Our results suggest that liver-specific ALDH2 inhibition may be an effective strategy for the treatment of alcohol user disorder with excessive drinking.\n                  </jats:p>","is_dataset_classified":null,"base_score":4.248495242049359,"endowment":4.248495242049359,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31792171","pmcid":"PMC6926021","openalex_id":"https://openalex.org/W2992633709","authors":[],"funders":[{"funder_name":"Intramural Program of NIAAA, NIH","grant_id":"0","title":null}],"total_grants":1,"fwci":4.2392,"citation_percentile":0.95202288,"influential_citations":0,"citation_trend":[{"year":2019,"count":1},{"year":2020,"count":5},{"year":2021,"count":11},{"year":2022,"count":13},{"year":2023,"count":9},{"year":2024,"count":10},{"year":2025,"count":15},{"year":2026,"count":5}],"oa_status":"bronze","license":"https://www.pnas.org/site/aboutpnas/licenses.xhtml","oa_locations":[{"url":"https://www.pnas.org/content/pnas/116/51/25974.full.pdf","host_type":"journal"},{"url":"https://www.pnas.org/content/pnas/116/51/25974.full.pdf","host_type":"publisher"},{"url":"http://www.pnas.org/syndication/doi/10.1073/pnas.1908137116","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.1908137116","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.1908137116","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31792171","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6926021","host_type":"repository"}],"fields_of_study":["Alcohol Consumption and Health Effects","Eicosanoids and Hypertension Pharmacology","Liver Disease Diagnosis and Treatment"],"mesh_terms":["Aldehyde Dehydrogenase, Mitochondrial","Acetaldehyde","Alanine Transaminase","Alcohol Drinking","Ethanol","Alcoholism","Animals","Interferon-gamma","Liver","Mice, Inbred C57BL","Neuroglia","Neurons","RNA, Messenger","Gene Deletion","Mice, Knockout","Chemokine CCL2","Mice","Transcriptome"],"keywords":["ALDH2","Acetaldehyde","Aldehyde dehydrogenase","Alcohol dehydrogenase","Ethanol metabolism","Ethanol","Metabolite","Alcohol","Liver injury","Alcohol tolerance","Chemistry","Biochemistry","Pharmacology","Internal medicine","Endocrinology","Biology","Medicine","Enzyme","Neuron","Alcohol Metabolism","Alcohol Use Disorder","Shaldh2"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T17:38:19.711167Z","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":[]}