Metabolic disease and ABHD6 alter the circulating bis(monoacylglycerol)phosphate profile in mice and humans
Bis(monoacylglycerol)phosphate (BMP) is a phospholipid that is crucial for lipid degradation and sorting in acidic organelles. Genetic and drug-induced lysosomal storage disorders (LSDs) are associated with increased BMP concentrations in tissues and in the circulation. Data on BMP in disorders othe...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-05-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520322719 |
| _version_ | 1831742269488627712 |
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| author | Gernot F. Grabner Nermeen Fawzy Maria A. Pribasnig Markus Trieb Ulrike Taschler Michael Holzer Martina Schweiger Heimo Wolinski Dagmar Kolb Angela Horvath Rolf Breinbauer Thomas Rülicke Roland Rabl Achim Lass Vanessa Stadlbauer Birgit Hutter-Paier Rudolf E. Stauber Peter Fickert Rudolf Zechner Gunther Marsche Thomas O. Eichmann Robert Zimmermann |
| author_facet | Gernot F. Grabner Nermeen Fawzy Maria A. Pribasnig Markus Trieb Ulrike Taschler Michael Holzer Martina Schweiger Heimo Wolinski Dagmar Kolb Angela Horvath Rolf Breinbauer Thomas Rülicke Roland Rabl Achim Lass Vanessa Stadlbauer Birgit Hutter-Paier Rudolf E. Stauber Peter Fickert Rudolf Zechner Gunther Marsche Thomas O. Eichmann Robert Zimmermann |
| author_sort | Gernot F. Grabner |
| collection | DOAJ |
| description | Bis(monoacylglycerol)phosphate (BMP) is a phospholipid that is crucial for lipid degradation and sorting in acidic organelles. Genetic and drug-induced lysosomal storage disorders (LSDs) are associated with increased BMP concentrations in tissues and in the circulation. Data on BMP in disorders other than LSDs, however, are scarce, and key enzymes regulating BMP metabolism remain elusive. Here, we demonstrate that common metabolic disorders and the intracellular BMP hydrolase α/β-hydrolase domain-containing 6 (ABHD6) affect BMP metabolism in mice and humans. In mice, dietary lipid overload strongly affects BMP concentration and FA composition in the liver and plasma, similar to what has been observed in LSDs. Notably, distinct changes in the BMP FA profile enable a clear distinction between lipid overload and drug-induced LSDs. Global deletion of ABHD6 increases circulating BMP concentrations but does not cause LSDs. In humans, nonalcoholic fatty liver disease and liver cirrhosis affect the serum BMP FA composition and concentration. Furthermore, we identified a patient with a loss-of-function mutation in the ABHD6 gene, leading to an altered circulating BMP profile. In conclusion, our results suggest that common metabolic diseases and ABHD6 affect BMP metabolism in mice and humans. |
| first_indexed | 2024-12-21T14:31:12Z |
| format | Article |
| id | doaj.art-6811fbb03319497cbbdc699b457cff47 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-21T14:31:12Z |
| publishDate | 2019-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-6811fbb03319497cbbdc699b457cff472022-12-21T19:00:29ZengElsevierJournal of Lipid Research0022-22752019-05-0160510201031Metabolic disease and ABHD6 alter the circulating bis(monoacylglycerol)phosphate profile in mice and humansGernot F. Grabner0Nermeen Fawzy1Maria A. Pribasnig2Markus Trieb3Ulrike Taschler4Michael Holzer5Martina Schweiger6Heimo Wolinski7Dagmar Kolb8Angela Horvath9Rolf Breinbauer10Thomas Rülicke11Roland Rabl12Achim Lass13Vanessa Stadlbauer14Birgit Hutter-Paier15Rudolf E. Stauber16Peter Fickert17Rudolf Zechner18Gunther Marsche19Thomas O. Eichmann20Robert Zimmermann21Institute of Molecular Biosciences, University of Graz, Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, Austria; BioTechMed-Graz Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, AustriaDivision of Pharmacology Otto Loewi Research Center, Medical University of Graz, Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, AustriaDivision of Pharmacology Otto Loewi Research Center, Medical University of Graz, Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, AustriaCore Facility Ultrastructure Analysis Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, Graz, AustriaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, AustriaInstitute of Organic Chemistry Graz University of Technology, Graz, Austria; BioTechMed-Graz Graz, AustriaInstitute of Laboratory Animal Science University of Veterinary Medicine Vienna, Vienna, AustriaQPS Austria GmbH, Grambach, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, Austria; BioTechMed-Graz Graz, AustriaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, AustriaQPS Austria GmbH, Grambach, AustriaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, AustriaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, Austria; BioTechMed-Graz Graz, AustriaDivision of Pharmacology Otto Loewi Research Center, Medical University of Graz, Graz, Austria; BioTechMed-Graz Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, Austria; Center for Explorative Lipidomics Graz, Austria; BioTechMed-Graz Graz, Austria; To whom correspondence should be addressed.Institute of Molecular Biosciences, University of Graz, Graz, Austria; BioTechMed-Graz Graz, AustriaBis(monoacylglycerol)phosphate (BMP) is a phospholipid that is crucial for lipid degradation and sorting in acidic organelles. Genetic and drug-induced lysosomal storage disorders (LSDs) are associated with increased BMP concentrations in tissues and in the circulation. Data on BMP in disorders other than LSDs, however, are scarce, and key enzymes regulating BMP metabolism remain elusive. Here, we demonstrate that common metabolic disorders and the intracellular BMP hydrolase α/β-hydrolase domain-containing 6 (ABHD6) affect BMP metabolism in mice and humans. In mice, dietary lipid overload strongly affects BMP concentration and FA composition in the liver and plasma, similar to what has been observed in LSDs. Notably, distinct changes in the BMP FA profile enable a clear distinction between lipid overload and drug-induced LSDs. Global deletion of ABHD6 increases circulating BMP concentrations but does not cause LSDs. In humans, nonalcoholic fatty liver disease and liver cirrhosis affect the serum BMP FA composition and concentration. Furthermore, we identified a patient with a loss-of-function mutation in the ABHD6 gene, leading to an altered circulating BMP profile. In conclusion, our results suggest that common metabolic diseases and ABHD6 affect BMP metabolism in mice and humans.http://www.sciencedirect.com/science/article/pii/S0022227520322719nonalcoholic fatty liver diseaseobesitylysosomal storage disordersphospholipidslysobisphosphatidic acidα/β-hydrolase domain-containing 6 |
| spellingShingle | Gernot F. Grabner Nermeen Fawzy Maria A. Pribasnig Markus Trieb Ulrike Taschler Michael Holzer Martina Schweiger Heimo Wolinski Dagmar Kolb Angela Horvath Rolf Breinbauer Thomas Rülicke Roland Rabl Achim Lass Vanessa Stadlbauer Birgit Hutter-Paier Rudolf E. Stauber Peter Fickert Rudolf Zechner Gunther Marsche Thomas O. Eichmann Robert Zimmermann Metabolic disease and ABHD6 alter the circulating bis(monoacylglycerol)phosphate profile in mice and humans Journal of Lipid Research nonalcoholic fatty liver disease obesity lysosomal storage disorders phospholipids lysobisphosphatidic acid α/β-hydrolase domain-containing 6 |
| title | Metabolic disease and ABHD6 alter the circulating bis(monoacylglycerol)phosphate profile in mice and humans |
| title_full | Metabolic disease and ABHD6 alter the circulating bis(monoacylglycerol)phosphate profile in mice and humans |
| title_fullStr | Metabolic disease and ABHD6 alter the circulating bis(monoacylglycerol)phosphate profile in mice and humans |
| title_full_unstemmed | Metabolic disease and ABHD6 alter the circulating bis(monoacylglycerol)phosphate profile in mice and humans |
| title_short | Metabolic disease and ABHD6 alter the circulating bis(monoacylglycerol)phosphate profile in mice and humans |
| title_sort | metabolic disease and abhd6 alter the circulating bis monoacylglycerol phosphate profile in mice and humans |
| topic | nonalcoholic fatty liver disease obesity lysosomal storage disorders phospholipids lysobisphosphatidic acid α/β-hydrolase domain-containing 6 |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520322719 |
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