{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:52:36Z","timestamp":1791237156414,"version":"4.1.0"},"reference-count":23,"publisher":"Radiation Research Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2026,4,27]]},"abstract":"<jats:p>Ionizing radiation poses a significant health risk to adolescent livers by disrupting lipid metabolism, yet protective mechanisms remain poorly understood. We investigated this using a pubertal mouse model exposed to localized X-irradiation. Our approach combined transcriptomics, lipidomics, and pharmacological modulation of lipophagy with 3-methylade-nine and rapamycin. We also introduced a high-fat diet (HFD) to explore its synergistic effects with radiation. Radiation exposure alone reduced liver mass, increased plasma transaminases [Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], caused intrahepatic lipid droplet retention, and impaired glucose tolerance. Lipidomics revealed significant accumulation of lysophosphatidylcholine, triglycerides, and diacylglycerols. Notably, combining high-fat diet with radiation synergistically worsened mild radiation-induced steatosis into severe hepatocellular damage, with sharply increased transaminases and insulin resistance. Mechanistically, radiation downregulated key lipophagy-related genes like ATGL and LC3B-II. Pharmacological inhibition of lipophagy worsened steatosis and liver dysfunction, while its activation improved lipid clearance and considerably reduced liver injury. Our findings establish lipophagy as a vital adaptive response to radiation-induced metabolic stress in the adolescent liver. This study highlights the combined toxic effects of environment and diet and suggests that boosting lipophagy could be an effective strategy to lessen the adverse health effects of radiation exposure in vulnerable young populations.<\/jats:p>","DOI":"10.1667\/rade-26-00008","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:30:52Z","timestamp":1787841052000},"page":"324-336","source":"Crossref","is-referenced-by-count":1,"title":["Lipophagy Mitigates Radiation-induced Liver Lipid Disorders and Damage in Adolescent Mice"],"prefix":"10.1667","volume":"206","author":[{"given":"Yu Feng","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Yu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze Lin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi Qi","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"1","doi-asserted-by":"publisher","unstructured":"Freddie Bray, Mathieu Laversanne, Hyuna Sung, et al.  \"CA Cancer J Clin.\"  74, \"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.\" 229 (2024)","DOI":"10.3322\/caac.21834"},{"key":"2","doi-asserted-by":"publisher","unstructured":"Ziqiang Zhang, Jun Wang, Ning Song, et al.  \"Front Public Health.\"  11, \"The global, regional, and national burden of stomach cancer among adolescents and young adults in 204 countries and territories, 1990\u20132019: A population-based study.\" (2023)","DOI":"10.3389\/fpubh.2023.1079248"},{"key":"3","doi-asserted-by":"publisher","unstructured":"Elysia Alvarez, Lisa Force, Rixing Xu, et al.  \"Lancet Oncol.\"  23, \"The global burden of adolescent and young adult cancer in 2019: a systematic analysis for the Global Burden of Disease Study 2019.\" 27 (2022)","DOI":"10.1016\/s1470-2045(21)00581-7"},{"key":"4","doi-asserted-by":"publisher","unstructured":"Zhong Li, Hengrui Liang, Wei Wang, et al.  \"J Hematol Oncol.\"  17, \"Global cancer statistics for adolescents and young adults: population based study.\" (2024)","DOI":"10.1186\/s13045-024-01623-9"},{"key":"5","doi-asserted-by":"publisher","unstructured":"Lisa Diller, Eric Chow, James Gurney, et al.  \"J Clin Oncol.\"  27, \"Chronic Disease in the Childhood Cancer Survivor Study Cohort: A Review of Published Findings.\" 2339 (2009)","DOI":"10.1200\/jco.2008.21.1953"},{"key":"6","doi-asserted-by":"publisher","unstructured":"Miranda Fidler, Sumit Gupta, Isabelle Soerjomataram, et al.  \"Lancet Oncol.\"  18, \"Cancer incidence and mortality among young adults aged 20\u201339 years worldwide in 2012: a population-based study.\" 1579 (2017)","DOI":"10.1016\/s1470-2045(17)30677-0"},{"key":"7","doi-asserted-by":"publisher","unstructured":"Annalisa Trama, Laura Botta, Roberto Foschi, et al.  \"The Lancet Oncology.\"  17, \"Survival of European adolescents and young adults diagnosed with cancer in 2000\u201307: population-based data from EUROCARE-5.\" 896 (2016)","DOI":"10.1016\/s1470-2045(16)00162-5"},{"key":"8","doi-asserted-by":"publisher","unstructured":"Edit Bardi, Ren\u00e9e Mulder, Elvira van Dalen, et al.  \"Cancer Treat Rev.\"  100, \"Late hepatic toxicity surveillance for survivors of childhood, adolescent and young adult cancer: Recommendations from the international late effects of childhood cancer guideline harmonization group.\" (2021)","DOI":"10.1016\/j.ctrv.2021.102296"},{"key":"9","doi-asserted-by":"publisher","unstructured":"Afshin Beheshti, Kaushik Chakravarty, Homer Fogle, et al.  \"Sci Rep.\"  9, \"Multi-omics analysis of multiple missions to space reveal a theme of lipid dysregulation in mouse liver.\" (2019)","DOI":"10.1038\/s41598-019-55869-2"},{"key":"10","doi-asserted-by":"publisher","unstructured":"Bing-Shen Huang, Shih-Chiang Huang, Fang-Hsin Chen, et al.  \"Life Sci.\"  2022, \"Pentadecapeptide BPC 157 efficiently reduces radiation-induced liver injury and lipid accumulation through Kruppel-like factor 4 upregulation both in vivo and in vitro.\" 310","DOI":"10.1016\/j.lfs.2022.121072"},{"key":"11","doi-asserted-by":"publisher","unstructured":"Malgorzata Lysek-Gladysinska, Anna Wieczorek, Anna Walaszczyk, et al.  \"Radiat Environment Biophys.\"  57, \"Long-term effects of low-dose mouse liver irradiation involve ultrastructural and biochemical changes in hepatocytes that depend on lipid metabolism.\" 123 (2018)","DOI":"10.1007\/s00411-018-0734-9"},{"key":"12","doi-asserted-by":"publisher","unstructured":"Jing Su, Qin Zhao, Zhuangzhuang Zheng, et al.  \"Antioxidants.\"  11, \"Prospective Application of Ferroptosis in Hypoxic Cells for Tumor Radiotherapy.\" (2022)","DOI":"10.3390\/antiox11050921"},{"key":"13","doi-asserted-by":"publisher","unstructured":"N. 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Singh  \"Annu Rev Nutr.\"  35, \"Autophagy and Lipid Droplets in the Liver.\" 215 (2015)","DOI":"10.1146\/annurev-nutr-071813-105336"},{"key":"14","doi-asserted-by":"publisher","unstructured":"Alina Grama, Alexandra Mititelu, S\u00eerbe Claudia, et al.  \"Front Immunol.\"  \"Immune-mediated cholangiopathies in children: the need to better understand the pathophysiology for finding the future possible treatment targets.\" 14 (2023)","DOI":"10.3389\/fimmu.2023.1206025"},{"key":"15","doi-asserted-by":"publisher","unstructured":"Katherine Byrnes, Sophia Blessinger, Niani Tiaye Bailey, et al.  \"Acta Pharmaceutica Sinica B.\"  12, \"Therapeutic regulation of autophagy in hepatic metabolism.\" 33 (2022)","DOI":"10.1016\/j.apsb.2021.07.021"},{"key":"16","doi-asserted-by":"publisher","unstructured":"Jieun Kim  and Youngmi Jung  \"Experiment Mol Med.\"  49, \"Radiation-induced liver disease: current understanding and future perspectives.\" e359 (2017)","DOI":"10.1038\/emm.2017.85"},{"key":"17","doi-asserted-by":"publisher","unstructured":"Ioanna Papandreou, Martin Benej, Nicholas Denko,  \"Cell Metabolism.\"  35, \"Unanticipated metabolic plasticity in response to chronic hypoxia.\" 381 (2023)","DOI":"10.1016\/j.cmet.2023.02.011"},{"key":"18","doi-asserted-by":"publisher","unstructured":"Alexander Kovalic, Glen Huang, Paul Thuluvath, et al.  \"Hepatology.\"  73, \"Reply.\" 2080 (2021)","DOI":"10.1002\/hep.31542"},{"key":"19","doi-asserted-by":"publisher","unstructured":"Jie Dong, Yahong Han, Ru Feng, et al.  \"Biomaterials.\"  2026, \"Smart microenvironment-activatable silybin nano-prodrug for precise NIR-II fluorescence monitoring and on-demand therapy of acute liver injury.\" 326","DOI":"10.1016\/j.biomaterials.2025.123673"},{"key":"20","doi-asserted-by":"publisher","unstructured":"Diego Toesca, Bulat Ibragimov, Amanda Koong, et al.  \"J Radiat Res.\"  59, \"Strategies for prediction and mitigation of radiation-induced liver toxicity.\" i40 (2018)","DOI":"10.1093\/jrr\/rrx104"},{"key":"21","doi-asserted-by":"publisher","unstructured":"Eugene Koay, Dawn Owen, Prajnan Das,  \"Sem Radiat Oncol.\"  28, \"Radiation-Induced Liver Disease and Modern Radiotherapy.\" 321 (2018)","DOI":"10.1016\/j.semradonc.2018.06.007"},{"key":"22","doi-asserted-by":"publisher","unstructured":"Eui Jung Jung, Ki Woon Sung, Tae Hyun Bae, et al.  \"Metabolism.\"  146, \"The N-degron pathway mediates lipophagy: The chemical modulation of lipophagy in obesity and NAFLD.\" (2023)","DOI":"10.1016\/j.metabol.2023.155644"},{"key":"23","doi-asserted-by":"publisher","unstructured":"Y. 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