Ether lipids, sphingolipids and toxic 1‐deoxyceramides as hallmarks for lean and obese type 2 diabetic patients
- 22 December 2020
- journal article
- research article
- Published by Wiley in Acta Physiologica
- Vol. 232 (1), e13610
- https://doi.org/10.1111/apha.13610
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.Keywords
Funding Information
- Vontobel-Stiftung
- Olga Mayenfisch Stiftung
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030‐184708, 31003A_166700/1, CRSII3_154405, 310030B_166686, CRSII3_160741)
- Swiss Life Stiftung für Chancenreichtum und Zukunft
- Fondation Ernst et Lucie Schmidheiny
- Fondation Leenaards
This publication has 72 references indexed in Scilit:
- Novel biomarkers for pre‐diabetes identified by metabolomicsMolecular Systems Biology, 2012
- A Phospholipidomic Analysis of All Defined Human Plasma LipoproteinsScientific Reports, 2011
- Sparse PLS discriminant analysis: biologically relevant feature selection and graphical displays for multiclass problemsBMC Bioinformatics, 2011
- Mass spectrometric analysis of long‐chain lipidsMass Spectrometry Reviews, 2010
- Deoxysphingoid bases as plasma markers in Diabetes mellitusLipids in Health and Disease, 2010
- Hereditary Sensory Neuropathy Type 1 Is Caused by the Accumulation of Two Neurotoxic Sphingolipids*Journal of Biological Chemistry, 2010
- Ceramide Synthase Inhibition by Fumonisin B1 Causes Accumulation of 1-DeoxysphinganineOnline Journal of Public Health Informatics, 2009
- Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetesThe Journal of Experimental Medicine, 2008
- Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomicsJournal of Lipid Research, 2008
- Acquired Obesity Is Associated with Changes in the Serum Lipidomic Profile Independent of Genetic Effects – A Monozygotic Twin StudyPLOS ONE, 2007