دورية أكاديمية
TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis.
العنوان: | TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis. |
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المؤلفون: | Petkevicius K; Bioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. kasparas.petkevicius@astrazeneca.com.; Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. kasparas.petkevicius@astrazeneca.com., Palmgren H; Bioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.; Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden., Glover MS; Dynamic Omics, Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA., Ahnmark A; Bioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Andréasson AC; Bioscience Cardiovascular, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Madeyski-Bengtson K; Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Kawana H; Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.; Advanced Research & Development Programs for Medical Innovation (AMED-LEAP), Tokyo, Japan., Allman EL; Dynamic Omics, Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA., Kaper D; Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden., Uhrbom M; Bioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Andersson L; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Aasehaug L; Bioscience Cardiovascular, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Forsström J; Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Wallin S; Bioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Ahlstedt I; Bioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Leke R; Bioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Karlsson D; Bioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., González-King H; Bioscience Cardiovascular, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Löfgren L; Translational Science and Experimental Medicine, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Nilsson R; Translational Science and Experimental Medicine, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Pellegrini G; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Kono N; Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan., Aoki J; Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.; Advanced Research & Development Programs for Medical Innovation (AMED-LEAP), Tokyo, Japan., Hess S; Dynamic Omics, Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA., Sienski G; Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Pilon M; Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden., Bohlooly-Y M; Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Maresca M; Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Peng XR; Bioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. |
المصدر: | Nature communications [Nat Commun] 2022 Oct 14; Vol. 13 (1), pp. 6020. Date of Electronic Publication: 2022 Oct 14. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [London] : Nature Pub. Group |
مواضيع طبية MeSH: | Non-alcoholic Fatty Liver Disease*/genetics , Non-alcoholic Fatty Liver Disease*/metabolism , Phosphatidylethanolamines*/metabolism, Animals ; Fatty Acids/metabolism ; Fatty Acids, Monounsaturated/metabolism ; Liver/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout |
مستخلص: | The fatty acid composition of phosphatidylethanolamine (PE) determines cellular metabolism, oxidative stress, and inflammation. However, our understanding of how cells regulate PE composition is limited. Here, we identify a genetic locus on mouse chromosome 11, containing two poorly characterized genes Tlcd1 and Tlcd2, that strongly influences PE composition. We generated Tlcd1/2 double-knockout (DKO) mice and found that they have reduced levels of hepatic monounsaturated fatty acid (MUFA)-containing PE species. Mechanistically, TLCD1/2 proteins act cell intrinsically to promote the incorporation of MUFAs into PEs. Furthermore, TLCD1/2 interact with the mitochondria in an evolutionarily conserved manner and regulate mitochondrial PE composition. Lastly, we demonstrate the biological relevance of our findings in dietary models of metabolic disease, where Tlcd1/2 DKO mice display attenuated development of non-alcoholic steatohepatitis compared to controls. Overall, we identify TLCD1/2 proteins as key regulators of cellular PE composition, with our findings having broad implications in understanding and treating disease. (© 2022. The Author(s).) |
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المشرفين على المادة: | 0 (Fatty Acids) 0 (Fatty Acids, Monounsaturated) 0 (Phosphatidylethanolamines) |
تواريخ الأحداث: | Date Created: 20221014 Date Completed: 20221018 Latest Revision: 20221206 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC9568529 |
DOI: | 10.1038/s41467-022-33735-6 |
PMID: | 36241646 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2041-1723 |
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DOI: | 10.1038/s41467-022-33735-6 |