Cargando…

Relationship between hepatic and mitochondrial ceramides: a novel in vivo method to track ceramide synthesis

Ceramides (CERs) are key intermediate sphingolipids implicated in contributing to mitochondrial dysfunction and the development of multiple metabolic conditions. Despite the growing evidence of CER role in disease risk, kinetic methods to measure CER turnover are lacking, particularly using in vivo...

Descripción completa

Detalles Bibliográficos
Autores principales: Mucinski, Justine M., McCaffrey, Jonas M., Rector, R. Scott, Kasumov, Takhar, Parks, Elizabeth J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10193228/
https://www.ncbi.nlm.nih.gov/pubmed/37028768
http://dx.doi.org/10.1016/j.jlr.2023.100366
_version_ 1785043795642941440
author Mucinski, Justine M.
McCaffrey, Jonas M.
Rector, R. Scott
Kasumov, Takhar
Parks, Elizabeth J.
author_facet Mucinski, Justine M.
McCaffrey, Jonas M.
Rector, R. Scott
Kasumov, Takhar
Parks, Elizabeth J.
author_sort Mucinski, Justine M.
collection PubMed
description Ceramides (CERs) are key intermediate sphingolipids implicated in contributing to mitochondrial dysfunction and the development of multiple metabolic conditions. Despite the growing evidence of CER role in disease risk, kinetic methods to measure CER turnover are lacking, particularly using in vivo models. The utility of orally administered (13)C(3), (15)N l-serine, dissolved in drinking water, was tested to quantify CER 18:1/16:0 synthesis in 10-week-old male and female C57Bl/6 mice. To generate isotopic labeling curves, animals consumed either a control diet or high-fat diet (HFD; n = 24/diet) for 2 weeks and varied in the duration of the consumption of serine-labeled water (0, 1, 2, 4, 7, or 12 days; n = 4 animals/day/diet). Unlabeled and labeled hepatic and mitochondrial CERs were quantified using liquid chromatography tandem MS. Total hepatic CER content did not differ between the two diet groups, whereas total mitochondrial CERs increased with HFD feeding (60%, P < 0.001). Within hepatic and mitochondrial pools, HFD induced greater saturated CER concentrations (P < 0.05) and significantly elevated absolute turnover of 16:0 mitochondrial CER (mitochondria: 59%, P < 0.001 vs. liver: 15%, P = 0.256). The data suggest cellular redistribution of CERs because of the HFD. These data demonstrate that a 2-week HFD alters the turnover and content of mitochondrial CERs. Given the growing data on CERs contributing to hepatic mitochondrial dysfunction and the progression of multiple metabolic diseases, this method may now be used to investigate how CER turnover is altered in these conditions.
format Online
Article
Text
id pubmed-10193228
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher American Society for Biochemistry and Molecular Biology
record_format MEDLINE/PubMed
spelling pubmed-101932282023-05-19 Relationship between hepatic and mitochondrial ceramides: a novel in vivo method to track ceramide synthesis Mucinski, Justine M. McCaffrey, Jonas M. Rector, R. Scott Kasumov, Takhar Parks, Elizabeth J. J Lipid Res Methods Ceramides (CERs) are key intermediate sphingolipids implicated in contributing to mitochondrial dysfunction and the development of multiple metabolic conditions. Despite the growing evidence of CER role in disease risk, kinetic methods to measure CER turnover are lacking, particularly using in vivo models. The utility of orally administered (13)C(3), (15)N l-serine, dissolved in drinking water, was tested to quantify CER 18:1/16:0 synthesis in 10-week-old male and female C57Bl/6 mice. To generate isotopic labeling curves, animals consumed either a control diet or high-fat diet (HFD; n = 24/diet) for 2 weeks and varied in the duration of the consumption of serine-labeled water (0, 1, 2, 4, 7, or 12 days; n = 4 animals/day/diet). Unlabeled and labeled hepatic and mitochondrial CERs were quantified using liquid chromatography tandem MS. Total hepatic CER content did not differ between the two diet groups, whereas total mitochondrial CERs increased with HFD feeding (60%, P < 0.001). Within hepatic and mitochondrial pools, HFD induced greater saturated CER concentrations (P < 0.05) and significantly elevated absolute turnover of 16:0 mitochondrial CER (mitochondria: 59%, P < 0.001 vs. liver: 15%, P = 0.256). The data suggest cellular redistribution of CERs because of the HFD. These data demonstrate that a 2-week HFD alters the turnover and content of mitochondrial CERs. Given the growing data on CERs contributing to hepatic mitochondrial dysfunction and the progression of multiple metabolic diseases, this method may now be used to investigate how CER turnover is altered in these conditions. American Society for Biochemistry and Molecular Biology 2023-04-05 /pmc/articles/PMC10193228/ /pubmed/37028768 http://dx.doi.org/10.1016/j.jlr.2023.100366 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Methods
Mucinski, Justine M.
McCaffrey, Jonas M.
Rector, R. Scott
Kasumov, Takhar
Parks, Elizabeth J.
Relationship between hepatic and mitochondrial ceramides: a novel in vivo method to track ceramide synthesis
title Relationship between hepatic and mitochondrial ceramides: a novel in vivo method to track ceramide synthesis
title_full Relationship between hepatic and mitochondrial ceramides: a novel in vivo method to track ceramide synthesis
title_fullStr Relationship between hepatic and mitochondrial ceramides: a novel in vivo method to track ceramide synthesis
title_full_unstemmed Relationship between hepatic and mitochondrial ceramides: a novel in vivo method to track ceramide synthesis
title_short Relationship between hepatic and mitochondrial ceramides: a novel in vivo method to track ceramide synthesis
title_sort relationship between hepatic and mitochondrial ceramides: a novel in vivo method to track ceramide synthesis
topic Methods
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10193228/
https://www.ncbi.nlm.nih.gov/pubmed/37028768
http://dx.doi.org/10.1016/j.jlr.2023.100366
work_keys_str_mv AT mucinskijustinem relationshipbetweenhepaticandmitochondrialceramidesanovelinvivomethodtotrackceramidesynthesis
AT mccaffreyjonasm relationshipbetweenhepaticandmitochondrialceramidesanovelinvivomethodtotrackceramidesynthesis
AT rectorrscott relationshipbetweenhepaticandmitochondrialceramidesanovelinvivomethodtotrackceramidesynthesis
AT kasumovtakhar relationshipbetweenhepaticandmitochondrialceramidesanovelinvivomethodtotrackceramidesynthesis
AT parkselizabethj relationshipbetweenhepaticandmitochondrialceramidesanovelinvivomethodtotrackceramidesynthesis