biostudies-literatureZalma BANIDDK NIH HHSNational Institute of Diabetes and Digestive and Kidney DiseasesVirginia and D K Ludwig Fund for Cancer Research108171https://www.ebi.ac.uk/biostudies/studies/S-EPMC11850126biostudies-literatureUnknown301(2)Amino acid starvation by the chemotherapy agent asparaginase is a potent activator of the integrated stress response (ISR) in the liver and can upregulate autophagy in some cell types. We hypothesized that autophagy-related 7 (ATG7), 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-Atg7KO) in mice before exposure to pegylated asparaginase for 5 days. 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, The Journal of biological chemistryAutophagy-related 7 (ATG7) regulates food intake and liver health during asparaginase exposure.PMC11850126R01 DK109714Rodriguez EMWek RCRodriguez-Polanco FCAnthony TGZalma BACararo-Lopes EWhite EFarooq SABhavsar CTIbrahim MLevy JLfalseAutophagy-related 7 (ATG7) regulates food intake and liver health during asparaginase exposure.Amino acid starvation by the chemotherapy agent asparaginase is a potent activator of the integrated stress response (ISR) in the liver and can upregulate autophagy in some cell types. We hypothesized that autophagy-related 7 (ATG7), 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-Atg7KO) in mice before exposure to pegylated asparaginase for 5 days. 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, 2025-01-01T00:00:00Z2025 Feb2025-04-18T21:20:44.673Z2025-04-07T09:18:11.216ZS-EPMC118501263979888110.1016/j.jbc.2025.108171