Ether lipids, sphingolipids and toxic 1‐deoxyceramides as hallmarks for lean and obese type 2 diabetic patients

Aim The worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further promote the development of T2D, and the accumulation of toxic lipid metabolites in serum and peripheral organs may contribute to the diabetic phe...

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Published inActa Physiologica Vol. 232; no. 1; pp. e13610 - n/a
Main Authors Hannich, J. Thomas, Loizides‐Mangold, Ursula, Sinturel, Flore, Harayama, Takeshi, Vandereycken, Bart, Saini, Camille, Gosselin, Pauline, Brulhart‐Meynet, Marie‐Claude, Robert, Maud, Chanon, Stephanie, Durand, Christine, Paz Montoya, Jonathan, David, Fabrice P. A., Guessous, Idris, Pataky, Zoltan, Golay, Alain, Jornayvaz, François R., Philippe, Jacques, Dermitzakis, Emmanouil T., Brown, Steven A., Lefai, Etienne, Riezman, Howard, Dibner, Charna
Format Journal Article
LanguageEnglish
Published England Wiley Subscription Services, Inc 01.05.2021
Wiley
Subjects
1‐deoxyceramide
Adipocytes
Adipose tissue
Cell culture
Cell differentiation
Cytotoxicity
Diabetes
Diabetes mellitus (non-insulin dependent)
Homeostasis
Life Sciences
lipid metabolism
lipidomics
Lipids
Mass spectroscopy
Obesity
Phenotypes
Phospholipids
Precision medicine
serum
Skeletal muscle
Sphingolipids
Type 2 diabetes in lean and obese subjects
visceral adipose tissue
1-deoxyceramide
serum
lipidomics
lipid metabolism
Type 2 diabetes in lean and obese subjects
visceral adipose tissue
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Abstract Aim The worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further promote the development of T2D, and the accumulation of toxic lipid metabolites in serum and peripheral organs may contribute to the diabetic phenotype. Methods To better understand the complex metabolic pattern of lean and obese T2D and non‐T2D individuals, we analysed the lipid profile of human serum, skeletal muscle and visceral adipose tissue of two cohorts by systematic mass spectrometry‐based lipid analysis. Results Lipid homeostasis was strongly altered in a disease‐ and tissue‐specific manner, allowing us to define T2D signatures associated with obesity from those that were obesity independent. Lipid changes encompassed lyso‐, diacyl‐ and ether‐phospholipids. Moreover, strong changes in sphingolipids included cytotoxic 1‐deoxyceramide accumulation in a disease‐specific manner in serum and visceral adipose tissue. The high amounts of non‐canonical 1‐deoxyceramide present in human adipose tissue most likely come from cell‐autonomous synthesis because 1‐deoxyceramide production increased upon differentiation to adipocytes in mouse cell culture experiments. Conclusion Taken together, the observed lipidome changes in obesity and T2D will facilitate the identification of T2D patient subgroups and represent an important step towards personalized medicine in diabetes.
AbstractList AimThe worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further promote the development of T2D, and the accumulation of toxic lipid metabolites in serum and peripheral organs may contribute to the diabetic phenotype.MethodsTo better understand the complex metabolic pattern of lean and obese T2D and non‐T2D individuals, we analysed the lipid profile of human serum, skeletal muscle and visceral adipose tissue of two cohorts by systematic mass spectrometry‐based lipid analysis.ResultsLipid homeostasis was strongly altered in a disease‐ and tissue‐specific manner, allowing us to define T2D signatures associated with obesity from those that were obesity independent. Lipid changes encompassed lyso‐, diacyl‐ and ether‐phospholipids. Moreover, strong changes in sphingolipids included cytotoxic 1‐deoxyceramide accumulation in a disease‐specific manner in serum and visceral adipose tissue. The high amounts of non‐canonical 1‐deoxyceramide present in human adipose tissue most likely come from cell‐autonomous synthesis because 1‐deoxyceramide production increased upon differentiation to adipocytes in mouse cell culture experiments.ConclusionTaken together, the observed lipidome changes in obesity and T2D will facilitate the identification of T2D patient subgroups and represent an important step towards personalized medicine in diabetes.
The worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further promote the development of T2D, and the accumulation of toxic lipid metabolites in serum and peripheral organs may contribute to the diabetic phenotype.AIMThe worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further promote the development of T2D, and the accumulation of toxic lipid metabolites in serum and peripheral organs may contribute to the diabetic phenotype.To better understand the complex metabolic pattern of lean and obese T2D and non-T2D individuals, we analysed the lipid profile of human serum, skeletal muscle and visceral adipose tissue of two cohorts by systematic mass spectrometry-based lipid analysis.METHODSTo better understand the complex metabolic pattern of lean and obese T2D and non-T2D individuals, we analysed the lipid profile of human serum, skeletal muscle and visceral adipose tissue of two cohorts by systematic mass spectrometry-based lipid analysis.Lipid homeostasis was strongly altered in a disease- and tissue-specific manner, allowing us to define T2D signatures associated with obesity from those that were obesity independent. Lipid changes encompassed lyso-, diacyl- and ether-phospholipids. Moreover, strong changes in sphingolipids included cytotoxic 1-deoxyceramide accumulation in a disease-specific manner in serum and visceral adipose tissue. The high amounts of non-canonical 1-deoxyceramide present in human adipose tissue most likely come from cell-autonomous synthesis because 1-deoxyceramide production increased upon differentiation to adipocytes in mouse cell culture experiments.RESULTSLipid homeostasis was strongly altered in a disease- and tissue-specific manner, allowing us to define T2D signatures associated with obesity from those that were obesity independent. Lipid changes encompassed lyso-, diacyl- and ether-phospholipids. Moreover, strong changes in sphingolipids included cytotoxic 1-deoxyceramide accumulation in a disease-specific manner in serum and visceral adipose tissue. The high amounts of non-canonical 1-deoxyceramide present in human adipose tissue most likely come from cell-autonomous synthesis because 1-deoxyceramide production increased upon differentiation to adipocytes in mouse cell culture experiments.Taken together, the observed lipidome changes in obesity and T2D will facilitate the identification of T2D patient subgroups and represent an important step towards personalized medicine in diabetes.CONCLUSIONTaken together, the observed lipidome changes in obesity and T2D will facilitate the identification of T2D patient subgroups and represent an important step towards personalized medicine in diabetes.
Aim The worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further promote the development of T2D, and the accumulation of toxic lipid metabolites in serum and peripheral organs may contribute to the diabetic phenotype. Methods To better understand the complex metabolic pattern of lean and obese T2D and non‐T2D individuals, we analysed the lipid profile of human serum, skeletal muscle and visceral adipose tissue of two cohorts by systematic mass spectrometry‐based lipid analysis. Results Lipid homeostasis was strongly altered in a disease‐ and tissue‐specific manner, allowing us to define T2D signatures associated with obesity from those that were obesity independent. Lipid changes encompassed lyso‐, diacyl‐ and ether‐phospholipids. Moreover, strong changes in sphingolipids included cytotoxic 1‐deoxyceramide accumulation in a disease‐specific manner in serum and visceral adipose tissue. The high amounts of non‐canonical 1‐deoxyceramide present in human adipose tissue most likely come from cell‐autonomous synthesis because 1‐deoxyceramide production increased upon differentiation to adipocytes in mouse cell culture experiments. Conclusion Taken together, the observed lipidome changes in obesity and T2D will facilitate the identification of T2D patient subgroups and represent an important step towards personalized medicine in diabetes.
AIM: The worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further promote the development of T2D, and the accumulation of toxic lipid metabolites in serum and peripheral organs may contribute to the diabetic phenotype. METHODS: To better understand the complex metabolic pattern of lean and obese T2D and non-T2D individuals, we analysed the lipid profile of human serum, skeletal muscle and visceral adipose tissue of two cohorts by systematic mass spectrometry-based lipid analysis. RESULTS: Lipid homeostasis was strongly altered in a disease- and tissue-specific manner, allowing us to define T2D signatures associated with obesity from those that were obesity independent. Lipid changes encompassed lyso-, diacyl- and ether-phospholipids. Moreover, strong changes in sphingolipids included cytotoxic 1-deoxyceramide accumulation in a disease-specific manner in serum and visceral adipose tissue. The high amounts of non-canonical 1-deoxyceramide present in human adipose tissue most likely come from cell-autonomous synthesis because 1-deoxyceramide production increased upon differentiation to adipocytes in mouse cell culture experiments. CONCLUSION: Taken together, the observed lipidome changes in obesity and T2D will facilitate the identification of T2D patient subgroups and represent an important step towards personalized medicine in diabetes.
The worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further promote the development of T2D, and the accumulation of toxic lipid metabolites in serum and peripheral organs may contribute to the diabetic phenotype. To better understand the complex metabolic pattern of lean and obese T2D and non-T2D individuals, we analysed the lipid profile of human serum, skeletal muscle and visceral adipose tissue of two cohorts by systematic mass spectrometry-based lipid analysis. Lipid homeostasis was strongly altered in a disease- and tissue-specific manner, allowing us to define T2D signatures associated with obesity from those that were obesity independent. Lipid changes encompassed lyso-, diacyl- and ether-phospholipids. Moreover, strong changes in sphingolipids included cytotoxic 1-deoxyceramide accumulation in a disease-specific manner in serum and visceral adipose tissue. The high amounts of non-canonical 1-deoxyceramide present in human adipose tissue most likely come from cell-autonomous synthesis because 1-deoxyceramide production increased upon differentiation to adipocytes in mouse cell culture experiments. Taken together, the observed lipidome changes in obesity and T2D will facilitate the identification of T2D patient subgroups and represent an important step towards personalized medicine in diabetes.
Author Loizides‐Mangold, Ursula
Gosselin, Pauline
Brulhart‐Meynet, Marie‐Claude
Riezman, Howard
Brown, Steven A.
Lefai, Etienne
Dermitzakis, Emmanouil T.
Dibner, Charna
Durand, Christine
Guessous, Idris
Pataky, Zoltan
Vandereycken, Bart
David, Fabrice P. A.
Saini, Camille
Paz Montoya, Jonathan
Golay, Alain
Sinturel, Flore
Jornayvaz, François R.
Hannich, J. Thomas
Robert, Maud
Philippe, Jacques
Harayama, Takeshi
Chanon, Stephanie
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ContentType Journal Article
Copyright 2021 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd
2021 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
Copyright © 2021 Scandinavian Physiological Society
Distributed under a Creative Commons Attribution 4.0 International License
Copyright_xml – notice: 2021 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd
– notice: 2021 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
– notice: Copyright © 2021 Scandinavian Physiological Society
– notice: Distributed under a Creative Commons Attribution 4.0 International License
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Issue 1
Keywords 1-deoxyceramide
serum
lipidomics
lipid metabolism
Type 2 diabetes in lean and obese subjects
visceral adipose tissue
Language English
License 2021 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
Distributed under a Creative Commons Attribution 4.0 International License: http://creativecommons.org/licenses/by/4.0
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c4300-61ffedbe33a88a081f6fbef2537e39d234cfaeb90e808aae0450e51dab4f5d043
Notes Funding information
This study was supported by the SNSF grants 31003A_166700/1 and 310030‐184708, the Vontobel Foundation, the Olga Mayenfisch Foundation, the Novartis Foundation for Medical‐Biological Research, EFSD/Novonordisk Programme for Diabetes Research in Europe, Leenaards Foundation, the Fondation Ernst et Lucie Schmidheiny, the Jubiläumsstiftung Swiss Life Foundation and the Fondation pour la Recherche sur le Cancer (C.D.); by SNSF grant CRSII3_154405 (H.R., C.D., E.L.); SNSF grant CRSII3_160741 (S.A.B., J.P, E.T.D); SNSF grant 310030B_166686 (H.R.), the NCCR Chemical Biology funded by the SNSF (H.R.), by the Bo & Kerstin Hjelt diabetes Foundation (U.L.‐M.) and by the Young Independent Investigator Grant SGED/SSED (F. S.).
J. Thomas Hannich, Ursula Loizides‐Mangold, and Flore Sinturel, contributed equally to the work.
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Snippet Aim The worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further...
The worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further promote...
AimThe worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further...
AIM: The worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further...
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SubjectTerms 1‐deoxyceramide
Adipocytes
Adipose tissue
Cell culture
Cell differentiation
Cytotoxicity
Diabetes
Diabetes mellitus (non-insulin dependent)
Homeostasis
Life Sciences
lipid metabolism
lipidomics
Lipids
Mass spectroscopy
Obesity
Phenotypes
Phospholipids
Precision medicine
serum
Skeletal muscle
Sphingolipids
Type 2 diabetes in lean and obese subjects
visceral adipose tissue
Title Ether lipids, sphingolipids and toxic 1‐deoxyceramides as hallmarks for lean and obese type 2 diabetic patients
URI https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fapha.13610
https://www.ncbi.nlm.nih.gov/pubmed/33351229
https://www.proquest.com/docview/2532405640
https://www.proquest.com/docview/2472111968
https://inserm.hal.science/inserm-03269069
Volume 232
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