Endogenous levels of 1-O-acylceramides increase upon acidic ceramidase deficiency and decrease due to loss of Dgat1 in a tissue-dependent manner.

Autor: Bayerle A; Lipid Pathobiochemistry Group, German Cancer Research Center, Heidelberg, Germany., Marsching C; Lipid Pathobiochemistry Group, German Cancer Research Center, Heidelberg, Germany; Center for Applied Research in Biomedical Mass Spectrometry (ABIMAS), Mannheim, Germany; Instrumental Analytics and Bioanalytics, Mannheim University of Applied Sciences, Mannheim, Germany; Center for Mass Spectrometry and Optical Spectroscopy (CeMOS), Mannheim University of Applied Sciences, Mannheim, Germany., Rabionet M; Lipid Pathobiochemistry Group, German Cancer Research Center, Heidelberg, Germany., Dworski S; Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada., Kamani MA; University Health Network, Toronto, Canada., Chitraju C; Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Cell Biology, Harvard Medical School, Boston, MA, USA., Gluchowski NL; Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Cell Biology, Harvard Medical School, Boston, MA, USA; Division of Gastroenterology and Nutrition, Boston Children's Hospital, Boston, MA, USA., Gabriel KR; Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Cell Biology, Harvard Medical School, Boston, MA, USA; Howard Hughes Medical Institute, Boston, MA, USA., Herzer S; Lipid Pathobiochemistry Group, German Cancer Research Center, Heidelberg, Germany., Jennemann R; Lipid Pathobiochemistry Group, German Cancer Research Center, Heidelberg, Germany., Levade T; Laboratoire de Biochimie Métabolique, Institut Fédératif de Biologie, CHU Purpan, INSERM UMR1037 CRCT, Toulouse, France., Medin JA; Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; University Health Network, Toronto, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Medical College of Wisconsin, Milwaukee, WI 53226, USA., Sandhoff R; Lipid Pathobiochemistry Group, German Cancer Research Center, Heidelberg, Germany; Center for Applied Research in Biomedical Mass Spectrometry (ABIMAS), Mannheim, Germany. Electronic address: r.sandhoff@dkfz.de.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular and cell biology of lipids [Biochim Biophys Acta Mol Cell Biol Lipids] 2020 Sep; Vol. 1865 (9), pp. 158741. Date of Electronic Publication: 2020 May 28.
DOI: 10.1016/j.bbalip.2020.158741
Abstrakt: Except for epidermis and liver, little is known about endogenous expression of 1-O-acylceramides (1-OACs) in mammalian tissue. Therefore, we screened several organs (brain, lung, liver, spleen, lymph nodes, heart, kidney, thymus, small intestine, and colon) from mice for the presence of 1-OACs by LC-MS 2 . In most organs, low levels of about 0.25-1.3 pmol 1-OACs/mg wet weight were recorded. Higher levels were detected in liver, small and large intestines, with about 4-13 pmol 1-OACs/mg wet weight. 1-OACs were esterified mainly with palmitic, stearic, or oleic acids. Esterification with saturated very long-chain fatty acids, as in epidermis, was not observed. Western-type diet induced 3-fold increased 1-OAC levels in mice livers while ceramides were unaltered. In a mouse model of Farber disease with a decrease of acid ceramidase activity, we observed a strong, up to 50-fold increase of 1-OACs in lung, thymus, and spleen. In contrast, 1-OAC levels were reduced 0.54-fold in liver. Only in lung 1-OAC levels correlated to changes in ceramide levels - indicating tissue-specific mechanisms of regulation. Glucosylceramide synthase deficiency in liver did not cause changes in 1-OAC or ceramide levels, whereas increased ceramide levels in glucosylceramide synthase-deficient small intestine caused an increase in 1-OAC levels. Deficiency of Dgat1 in mice resulted in a reduction of 1-OACs to 30% in colon, but not in small intestine and liver, going along with constant free ceramides levels. From these data, we conclude that Dgat1 as well as lysosomal lipid metabolism contribute in vivo to homeostatic 1-OAC levels in an organ-specific manner.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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