Blocking Lipid Uptake Pathways Does not Prevent Toxicity in Adipose Triglyceride Lipase (ATGL) Deficiency
Lipid accumulation in nonadipose tissues can cause lipotoxicity, leading to cell death and severe organ dysfunction. Adipose triglyceride lipase (ATGL) deficiency causes human neutral lipid storage disease and leads to cardiomyopathy; ATGL deficiency has no current treatment. One possible approach t...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227522001079 |
| _version_ | 1811304784676782080 |
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| author | Jide Oluwadare Ainara G. Cabodevilla Ni-Huiping Son Yunying Hu Adam E. Mullick Michael Verano Jose O. Alemán Ravichandran Ramasamy Ira J. Goldberg |
| author_facet | Jide Oluwadare Ainara G. Cabodevilla Ni-Huiping Son Yunying Hu Adam E. Mullick Michael Verano Jose O. Alemán Ravichandran Ramasamy Ira J. Goldberg |
| author_sort | Jide Oluwadare |
| collection | DOAJ |
| description | Lipid accumulation in nonadipose tissues can cause lipotoxicity, leading to cell death and severe organ dysfunction. Adipose triglyceride lipase (ATGL) deficiency causes human neutral lipid storage disease and leads to cardiomyopathy; ATGL deficiency has no current treatment. One possible approach to alleviate this disorder has been to alter the diet and reduce the supply of dietary lipids and, hence, myocardial lipid uptake. However, in this study, when we supplied cardiac Atgl KO mice a low- or high-fat diet, we found that heart lipid accumulation, heart dysfunction, and death were not altered. We next deleted lipid uptake pathways in the ATGL-deficient mice through the generation of double KO mice also deficient in either cardiac lipoprotein lipase or cluster of differentiation 36, which is involved in an lipoprotein lipase-independent pathway for FA uptake in the heart. We show that neither deletion ameliorated ATGL-deficient heart dysfunction. Similarly, we determined that non-lipid-containing media did not prevent lipid accumulation by cultured myocytes; rather, the cells switched to increased de novo FA synthesis. Thus, we conclude that pathological storage of lipids in ATGL deficiency cannot be corrected by reducing heart lipid uptake. |
| first_indexed | 2024-04-13T08:14:12Z |
| format | Article |
| id | doaj.art-f665ac1d40554a758d5215f1f0e19a98 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-04-13T08:14:12Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-f665ac1d40554a758d5215f1f0e19a982022-12-22T02:54:52ZengElsevierJournal of Lipid Research0022-22752022-11-016311100274Blocking Lipid Uptake Pathways Does not Prevent Toxicity in Adipose Triglyceride Lipase (ATGL) DeficiencyJide Oluwadare0Ainara G. Cabodevilla1Ni-Huiping Son2Yunying Hu3Adam E. Mullick4Michael Verano5Jose O. Alemán6Ravichandran Ramasamy7Ira J. Goldberg8Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine, New York, NY, USADivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine, New York, NY, USADivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine, New York, NY, USADivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine, New York, NY, USACardiovascular Drug Discovery, Ionis Pharmaceuticals Inc., Carlsbad, CA, USADivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine, New York, NY, USADivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine, New York, NY, USADivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine, New York, NY, USADivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA; For correspondence: Ira J. GoldbergLipid accumulation in nonadipose tissues can cause lipotoxicity, leading to cell death and severe organ dysfunction. Adipose triglyceride lipase (ATGL) deficiency causes human neutral lipid storage disease and leads to cardiomyopathy; ATGL deficiency has no current treatment. One possible approach to alleviate this disorder has been to alter the diet and reduce the supply of dietary lipids and, hence, myocardial lipid uptake. However, in this study, when we supplied cardiac Atgl KO mice a low- or high-fat diet, we found that heart lipid accumulation, heart dysfunction, and death were not altered. We next deleted lipid uptake pathways in the ATGL-deficient mice through the generation of double KO mice also deficient in either cardiac lipoprotein lipase or cluster of differentiation 36, which is involved in an lipoprotein lipase-independent pathway for FA uptake in the heart. We show that neither deletion ameliorated ATGL-deficient heart dysfunction. Similarly, we determined that non-lipid-containing media did not prevent lipid accumulation by cultured myocytes; rather, the cells switched to increased de novo FA synthesis. Thus, we conclude that pathological storage of lipids in ATGL deficiency cannot be corrected by reducing heart lipid uptake.http://www.sciencedirect.com/science/article/pii/S0022227522001079CD36dietary fatlipid accumulationlipotoxicitystorage diseasesLpL |
| spellingShingle | Jide Oluwadare Ainara G. Cabodevilla Ni-Huiping Son Yunying Hu Adam E. Mullick Michael Verano Jose O. Alemán Ravichandran Ramasamy Ira J. Goldberg Blocking Lipid Uptake Pathways Does not Prevent Toxicity in Adipose Triglyceride Lipase (ATGL) Deficiency Journal of Lipid Research CD36 dietary fat lipid accumulation lipotoxicity storage diseases LpL |
| title | Blocking Lipid Uptake Pathways Does not Prevent Toxicity in Adipose Triglyceride Lipase (ATGL) Deficiency |
| title_full | Blocking Lipid Uptake Pathways Does not Prevent Toxicity in Adipose Triglyceride Lipase (ATGL) Deficiency |
| title_fullStr | Blocking Lipid Uptake Pathways Does not Prevent Toxicity in Adipose Triglyceride Lipase (ATGL) Deficiency |
| title_full_unstemmed | Blocking Lipid Uptake Pathways Does not Prevent Toxicity in Adipose Triglyceride Lipase (ATGL) Deficiency |
| title_short | Blocking Lipid Uptake Pathways Does not Prevent Toxicity in Adipose Triglyceride Lipase (ATGL) Deficiency |
| title_sort | blocking lipid uptake pathways does not prevent toxicity in adipose triglyceride lipase atgl deficiency |
| topic | CD36 dietary fat lipid accumulation lipotoxicity storage diseases LpL |
| url | http://www.sciencedirect.com/science/article/pii/S0022227522001079 |
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