{"doi":"10.2337/db23-0357","title":"Roles of Activin A and Gpnmb in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)","abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as nonalcoholic fatty liver disease [NAFLD]) and metabolic dysfunction-associated steatohepatitis (MASH, formerly known as nonalcoholic steatohepatitis [NASH]) are leading chronic liver diseases, driving cirrhosis, hepatocellular carcinoma, and mortality. MASLD/MASH is associated with increased senescence proteins, including Activin A, and senolytics have been proposed as a therapeutic approach. To test the role of Activin A, we induced hepatic expression of Activin A in a murine MASLD/MASH model. Surprisingly, overexpression of hepatic Activin A dramatically mitigated MASLD, reducing liver steatosis and inflammation as well as systemic fat accumulation, while improving insulin sensitivity. Further studies identified a dramatic decrease in the lipid-associated macrophages marker glycoprotein NMB (Gpnmb) by Activin A, and Gpnmb knockdown in the same model produced similar benefits and transcriptional changes to Activin A expression. These studies reveal a surprising protective role for Activin A in MASLD and the potential for SASP proteins to have context-specific beneficial effects. Moreover, they implicate both Activin A and Gpnmb as potential therapeutic targets for this condition.","journal":"Diabetes","year":2023,"id":329974,"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":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":920523,"name":"Armen Yerevanian","orcid":"0000-0003-4985-1028","position":1,"is_corresponding":false},{"id":476760,"name":"Maria Westerhoff","orcid":"0000-0002-3094-0111","position":2,"is_corresponding":false},{"id":426022,"name":"Margaret H. Hastings","orcid":"0000-0001-9333-5210","position":3,"is_corresponding":false},{"id":1053173,"name":"Justin Ralph Baldovino Guerra","orcid":"0000-0001-8507-5922","position":4,"is_corresponding":false},{"id":348821,"name":"Meng Zhao","orcid":"0000-0002-5415-8335","position":5,"is_corresponding":false},{"id":348824,"name":"Katrin J. Svensson","orcid":"0000-0001-5376-5128","position":6,"is_corresponding":false},{"id":246025,"name":"Bishuang Cai","orcid":"0000-0002-2047-9923","position":7,"is_corresponding":false},{"id":299215,"name":"Alexander A. Soukas","orcid":"0000-0002-9100-2436","position":8,"is_corresponding":false},{"id":294916,"name":"Anthony Rosenzweig","orcid":"0000-0001-6387-0386","position":9,"is_corresponding":false},{"id":1053172,"name":"Huan Liu","orcid":"0000-0001-5527-1295","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T01:09:05.843139Z","pmid":"37934943","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":[]}