Cargando…

Serum dihydroceramides correlate with insulin sensitivity in humans and decrease insulin sensitivity in vitro

Serum ceramides, especially C16:0 and C18:0 species, are linked to CVD risk and insulin resistance, but details of this association are not well understood. We performed this study to quantify a broad range of serum sphingolipids in individuals spanning the physiologic range of insulin sensitivity a...

Descripción completa

Detalles Bibliográficos
Autores principales: Zarini, Simona, Brozinick, Joseph T., Zemski Berry, Karin A., Garfield, Amanda, Perreault, Leigh, Kerege, Anna, Bui, Hai Hoang, Sanders, Phil, Siddall, Parker, Kuo, Ming Shang, Bergman, Bryan C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508341/
https://www.ncbi.nlm.nih.gov/pubmed/36030929
http://dx.doi.org/10.1016/j.jlr.2022.100270
_version_ 1784796995651633152
author Zarini, Simona
Brozinick, Joseph T.
Zemski Berry, Karin A.
Garfield, Amanda
Perreault, Leigh
Kerege, Anna
Bui, Hai Hoang
Sanders, Phil
Siddall, Parker
Kuo, Ming Shang
Bergman, Bryan C.
author_facet Zarini, Simona
Brozinick, Joseph T.
Zemski Berry, Karin A.
Garfield, Amanda
Perreault, Leigh
Kerege, Anna
Bui, Hai Hoang
Sanders, Phil
Siddall, Parker
Kuo, Ming Shang
Bergman, Bryan C.
author_sort Zarini, Simona
collection PubMed
description Serum ceramides, especially C16:0 and C18:0 species, are linked to CVD risk and insulin resistance, but details of this association are not well understood. We performed this study to quantify a broad range of serum sphingolipids in individuals spanning the physiologic range of insulin sensitivity and to determine if dihydroceramides cause insulin resistance in vitro. As expected, we found that serum triglycerides were significantly greater in individuals with obesity and T2D compared with athletes and lean individuals. Serum ceramides were not significantly different within groups but, using all ceramide data relative to insulin sensitivity as a continuous variable, we observed significant inverse relationships between C18:0, C20:0, and C22:0 species and insulin sensitivity. Interestingly, we found that total serum dihydroceramides and individual species were significantly greater in individuals with obesity and T2D compared with athletes and lean individuals, with C18:0 species showing the strongest inverse relationship to insulin sensitivity. Finally, we administered a physiological mix of dihydroceramides to primary myotubes and found decreased insulin sensitivity in vitro without changing the overall intracellular sphingolipid content, suggesting a direct effect on insulin resistance. These data extend what is known regarding serum sphingolipids and insulin resistance and show the importance of serum dihydroceramides to predict and promote insulin resistance in humans.
format Online
Article
Text
id pubmed-9508341
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher American Society for Biochemistry and Molecular Biology
record_format MEDLINE/PubMed
spelling pubmed-95083412022-09-30 Serum dihydroceramides correlate with insulin sensitivity in humans and decrease insulin sensitivity in vitro Zarini, Simona Brozinick, Joseph T. Zemski Berry, Karin A. Garfield, Amanda Perreault, Leigh Kerege, Anna Bui, Hai Hoang Sanders, Phil Siddall, Parker Kuo, Ming Shang Bergman, Bryan C. J Lipid Res Research Article Serum ceramides, especially C16:0 and C18:0 species, are linked to CVD risk and insulin resistance, but details of this association are not well understood. We performed this study to quantify a broad range of serum sphingolipids in individuals spanning the physiologic range of insulin sensitivity and to determine if dihydroceramides cause insulin resistance in vitro. As expected, we found that serum triglycerides were significantly greater in individuals with obesity and T2D compared with athletes and lean individuals. Serum ceramides were not significantly different within groups but, using all ceramide data relative to insulin sensitivity as a continuous variable, we observed significant inverse relationships between C18:0, C20:0, and C22:0 species and insulin sensitivity. Interestingly, we found that total serum dihydroceramides and individual species were significantly greater in individuals with obesity and T2D compared with athletes and lean individuals, with C18:0 species showing the strongest inverse relationship to insulin sensitivity. Finally, we administered a physiological mix of dihydroceramides to primary myotubes and found decreased insulin sensitivity in vitro without changing the overall intracellular sphingolipid content, suggesting a direct effect on insulin resistance. These data extend what is known regarding serum sphingolipids and insulin resistance and show the importance of serum dihydroceramides to predict and promote insulin resistance in humans. American Society for Biochemistry and Molecular Biology 2022-08-27 /pmc/articles/PMC9508341/ /pubmed/36030929 http://dx.doi.org/10.1016/j.jlr.2022.100270 Text en © 2022 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 Research Article
Zarini, Simona
Brozinick, Joseph T.
Zemski Berry, Karin A.
Garfield, Amanda
Perreault, Leigh
Kerege, Anna
Bui, Hai Hoang
Sanders, Phil
Siddall, Parker
Kuo, Ming Shang
Bergman, Bryan C.
Serum dihydroceramides correlate with insulin sensitivity in humans and decrease insulin sensitivity in vitro
title Serum dihydroceramides correlate with insulin sensitivity in humans and decrease insulin sensitivity in vitro
title_full Serum dihydroceramides correlate with insulin sensitivity in humans and decrease insulin sensitivity in vitro
title_fullStr Serum dihydroceramides correlate with insulin sensitivity in humans and decrease insulin sensitivity in vitro
title_full_unstemmed Serum dihydroceramides correlate with insulin sensitivity in humans and decrease insulin sensitivity in vitro
title_short Serum dihydroceramides correlate with insulin sensitivity in humans and decrease insulin sensitivity in vitro
title_sort serum dihydroceramides correlate with insulin sensitivity in humans and decrease insulin sensitivity in vitro
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508341/
https://www.ncbi.nlm.nih.gov/pubmed/36030929
http://dx.doi.org/10.1016/j.jlr.2022.100270
work_keys_str_mv AT zarinisimona serumdihydroceramidescorrelatewithinsulinsensitivityinhumansanddecreaseinsulinsensitivityinvitro
AT brozinickjosepht serumdihydroceramidescorrelatewithinsulinsensitivityinhumansanddecreaseinsulinsensitivityinvitro
AT zemskiberrykarina serumdihydroceramidescorrelatewithinsulinsensitivityinhumansanddecreaseinsulinsensitivityinvitro
AT garfieldamanda serumdihydroceramidescorrelatewithinsulinsensitivityinhumansanddecreaseinsulinsensitivityinvitro
AT perreaultleigh serumdihydroceramidescorrelatewithinsulinsensitivityinhumansanddecreaseinsulinsensitivityinvitro
AT keregeanna serumdihydroceramidescorrelatewithinsulinsensitivityinhumansanddecreaseinsulinsensitivityinvitro
AT buihaihoang serumdihydroceramidescorrelatewithinsulinsensitivityinhumansanddecreaseinsulinsensitivityinvitro
AT sandersphil serumdihydroceramidescorrelatewithinsulinsensitivityinhumansanddecreaseinsulinsensitivityinvitro
AT siddallparker serumdihydroceramidescorrelatewithinsulinsensitivityinhumansanddecreaseinsulinsensitivityinvitro
AT kuomingshang serumdihydroceramidescorrelatewithinsulinsensitivityinhumansanddecreaseinsulinsensitivityinvitro
AT bergmanbryanc serumdihydroceramidescorrelatewithinsulinsensitivityinhumansanddecreaseinsulinsensitivityinvitro