{"doi":"10.1016/j.jbc.2025.108171","title":"Autophagy-related 7 (ATG7) regulates food intake and liver health during asparaginase exposure","abstract":"Amino acid starvation by the chemotherapy agent asparaginase is a potent activator of the integrated stress response (ISR) in liver and can upregulate autophagy in some cell types. We hypothesized that autophagy related 7 (ATG 7 ), a protein that is essential for autophagy and an ISR target gene, was necessary during exposure to asparaginase to maintain liver health. We knocked down Atg7 systemically ( Atg7 Δ/Δ ) or in hepatocytes only (ls- Atg7 KO) in mice before exposure to pegylated asparaginase for 5 d. Intact mice injected with asparaginase lost body weight due to reduced food intake and increased energy expenditure. Systemic Atg7 ablation reduced liver protein synthesis and increased liver injury in vehicle-injected mice, but did not further reduce liver protein synthesis, exacerbate steatosis or liver injury, or alter energy expenditure following 5 d asparaginase exposure. Atg7 Δ/Δ mice were unexpectantly protected from asparaginase-induced anorexia and weight loss. This protection corresponded with reduced phosphorylation of hepatic GCN2 and blunted increases in ISR gene targets including growth differentiation factor 15 (GDF15), a negative regulator of food intake. Interestingly, asparaginase elevated serum GDF15 and reduced food intake in ls- Atg7 KO mice, similar to intact mice. Liver triglycerides and production of the hepatokine fibroblast growth factor 21, another ISR gene target, were suppressed in asparaginase-exposed Atg7 Δ/Δ and ls- Atg7 KO mice. This work identifies a bidirectional relationship between autophagy and the ISR in the liver during asparaginase, affecting food intake and liver health.","journal":"Journal of Biological Chemistry","year":2025,"id":518808,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9603,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1213421,"name":"Maria Ibrahim","orcid":"0009-0004-5738-5252","position":1,"is_corresponding":false},{"id":1386697,"name":"Flavio C. Rodriguez-Polanco","orcid":"0000-0002-0353-6420","position":2,"is_corresponding":false},{"id":1386698,"name":"Chintan T. Bhavsar","orcid":"0009-0001-8180-6238","position":3,"is_corresponding":false},{"id":294586,"name":"Esther Rodríguez","orcid":"0000-0003-1837-1005","position":4,"is_corresponding":false},{"id":834138,"name":"Eduardo Cararo Lopes","orcid":"0000-0002-5316-5146","position":5,"is_corresponding":false},{"id":1386699,"name":"Saad A. Farooq","orcid":"0000-0003-0895-4514","position":6,"is_corresponding":false},{"id":473005,"name":"Jordan L. Levy","orcid":"0000-0001-6494-2433","position":7,"is_corresponding":false},{"id":337624,"name":"Ronald C. Wek","orcid":"0000-0002-2087-5504","position":8,"is_corresponding":false},{"id":244442,"name":"Eileen White","orcid":"0000-0003-2961-3065","position":9,"is_corresponding":false},{"id":473007,"name":"Tracy G. Anthony","orcid":"0000-0002-8586-5884","position":10,"is_corresponding":false},{"id":473004,"name":"Brian A. Zalma","orcid":"0000-0002-9424-5898","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T02:49:14.184995Z","pmid":"39798881","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":[]}