دورية أكاديمية
Mitochondrial ACSS1-K635 acetylation knock-in mice exhibit altered metabolism, cell senescence, and nonalcoholic fatty liver disease.
| العنوان: | Mitochondrial ACSS1-K635 acetylation knock-in mice exhibit altered metabolism, cell senescence, and nonalcoholic fatty liver disease. |
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| المؤلفون: | Xu G; Department of Radiation Oncology, Mays Cancer Center at UT Health San Antonio MD Anderson, Joe R. and Teresa Lozano Long School of Medicine, UT Health San Antonio, San Antonio, TX, USA.; Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, TX, USA., Quan S; Department of Radiation Oncology, Robert Lurie Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Schell J; Department of Radiation Oncology, Mays Cancer Center at UT Health San Antonio MD Anderson, Joe R. and Teresa Lozano Long School of Medicine, UT Health San Antonio, San Antonio, TX, USA.; Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, TX, USA., Gao Y; Department of Radiation Oncology, Robert Lurie Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Varmazyad M; Department of Radiation Oncology, Mays Cancer Center at UT Health San Antonio MD Anderson, Joe R. and Teresa Lozano Long School of Medicine, UT Health San Antonio, San Antonio, TX, USA.; Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, TX, USA., Sreenivas P; Department of Radiation Oncology, Mays Cancer Center at UT Health San Antonio MD Anderson, Joe R. and Teresa Lozano Long School of Medicine, UT Health San Antonio, San Antonio, TX, USA.; Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, TX, USA., Cruz D; Department of Radiation Oncology, Mays Cancer Center at UT Health San Antonio MD Anderson, Joe R. and Teresa Lozano Long School of Medicine, UT Health San Antonio, San Antonio, TX, USA.; Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, TX, USA., Jiang H; Department of Radiation Oncology, Mays Cancer Center at UT Health San Antonio MD Anderson, Joe R. and Teresa Lozano Long School of Medicine, UT Health San Antonio, San Antonio, TX, USA.; Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, TX, USA., Pan M; Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, TX, USA., Han X; Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, TX, USA., Palavicini JP; Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, TX, USA.; Division of Diabetes, UT Health San Antonio, San Antonio, TX, USA., Zhao P; Department of Biochemistry and Structural Biology, UT Health San Antonio, San Antonio, TX, USA., Sun X; Department of Pharmacology, Mays Cancer Center, Transplant Center, UT Health San Antonio, San Antonio, TX, USA., Marchant ED; Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, TX, USA.; Department of Biochemistry and Structural Biology, UT Health San Antonio, San Antonio, TX, USA., Rasmussen BB; Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, TX, USA.; Department of Biochemistry and Structural Biology, UT Health San Antonio, San Antonio, TX, USA., Li G; Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, TX, USA., Katsumura S; Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, TX, USA.; Department of Molecular Medicine, UT Health San Antonio, San Antonio, TX, USA., Morita M; Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, TX, USA.; Department of Molecular Medicine, UT Health San Antonio, San Antonio, TX, USA.; Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), Osaka University, Suita, Osaka 565-0871, Japan., Munkácsy E; Department of Radiation Oncology, Mays Cancer Center at UT Health San Antonio MD Anderson, Joe R. and Teresa Lozano Long School of Medicine, UT Health San Antonio, San Antonio, TX, USA.; Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, TX, USA., Horikoshi N; Department of Radiation Oncology, Mays Cancer Center at UT Health San Antonio MD Anderson, Joe R. and Teresa Lozano Long School of Medicine, UT Health San Antonio, San Antonio, TX, USA.; Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, TX, USA., Chocron ES; Department of Radiation Oncology, Mays Cancer Center at UT Health San Antonio MD Anderson, Joe R. and Teresa Lozano Long School of Medicine, UT Health San Antonio, San Antonio, TX, USA.; Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, TX, USA., Gius D; Department of Radiation Oncology, Mays Cancer Center at UT Health San Antonio MD Anderson, Joe R. and Teresa Lozano Long School of Medicine, UT Health San Antonio, San Antonio, TX, USA.; Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, TX, USA. |
| المصدر: | Science advances [Sci Adv] 2024 May 17; Vol. 10 (20), pp. eadj5942. Date of Electronic Publication: 2024 May 17. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : American Association for the Advancement of Science, [2015]- |
| مواضيع طبية MeSH: | Non-alcoholic Fatty Liver Disease*/metabolism , Non-alcoholic Fatty Liver Disease*/genetics , Non-alcoholic Fatty Liver Disease*/pathology , Cellular Senescence*/genetics , Mitochondria*/metabolism , Stearoyl-CoA Desaturase*/metabolism , Stearoyl-CoA Desaturase*/genetics, Animals ; Mice ; Acetylation ; Male ; Acetate-CoA Ligase/metabolism ; Acetate-CoA Ligase/genetics ; Gene Knock-In Techniques ; Liver/metabolism ; Liver/pathology ; Lipid Metabolism ; Sirtuin 3/metabolism ; Sirtuin 3/genetics ; Disease Models, Animal ; Coenzyme A Ligases ; Fatty Acid Synthase, Type I |
| مستخلص: | Acetyl-CoA synthetase short-chain family member 1 (ACSS1) uses acetate to generate mitochondrial acetyl-CoA and is regulated by deacetylation by sirtuin 3. We generated an ACSS1-acetylation (Ac) mimic mouse, where lysine-635 was mutated to glutamine (K635Q). Male Acss1 K635Q/K635Q mice were smaller with higher metabolic rate and blood acetate and decreased liver/serum ATP and lactate levels. After a 48-hour fast, Acss1 K635Q/K635Q mice presented hypothermia and liver aberrations, including enlargement, discoloration, lipid droplet accumulation, and microsteatosis, consistent with nonalcoholic fatty liver disease (NAFLD). RNA sequencing analysis suggested dysregulation of fatty acid metabolism, cellular senescence, and hepatic steatosis networks, consistent with NAFLD. Fasted Acss1 K635Q/K635Q mouse livers showed increased fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1), both associated with NAFLD, and increased carbohydrate response element-binding protein binding to Fasn and Scd1 enhancer regions. Last, liver lipidomics showed elevated ceramide, lysophosphatidylethanolamine, and lysophosphatidylcholine, all associated with NAFLD. Thus, we propose that ACSS1-K635-Ac dysregulation leads to aberrant lipid metabolism, cellular senescence, and NAFLD. |
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| معلومات مُعتمدة: | P30 AG013319 United States AG NIA NIH HHS; T32 AG021890 United States AG NIA NIH HHS |
| المشرفين على المادة: | 0 (Scd1 protein, mouse) 0 (ACSL1 protein, mouse) 0 (Fasn protein, mouse) |
| تواريخ الأحداث: | Date Created: 20240517 Date Completed: 20240517 Latest Revision: 20240717 |
| رمز التحديث: | 20240717 |
| مُعرف محوري في PubMed: | PMC11100568 |
| DOI: | 10.1126/sciadv.adj5942 |
| PMID: | 38758779 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2375-2548 |
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| DOI: | 10.1126/sciadv.adj5942 |