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Cell Rep. 2017 Feb 28;18(9):2269-2279. doi: 10.1016/j.celrep.2017.02.019.

Plasma Dihydroceramides Are Diabetes Susceptibility Biomarker Candidates in Mice and Humans.

Author information

1
Vital-IT Group, SIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland; Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland.
2
Unité de Biologie Fonctionnelle et Adaptative (BFA), CNRS UMR 8251, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris, France.
3
INSERM, Sorbonne Paris Cité, Centre de Recherce des Cordeliers (CRC), UMR_S 1138, 75006 Paris, France; UPMC, Sorbonne Universités, Centre de Recherce des Cordeliers (CRC), UMR_S 1138, 75006 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Centre de Recherche des Cordeliers (CRC), UMR_S 1138, 75006 Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Centre de Recherches des Cordeliers (CRC), UMR_S 1138, 75006 Paris, France.
4
Department of Medicine, Internal Medicine, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland.
5
Recherche de Découverte, PIT Métabolisme, Institut de Recherche Servier (IdRS), 92150 Suresnes, France.
6
Biomedical and Scientific Consulting, 55130 Mainz, Germany.
7
Diabetes Research, Islet Biology Cluster, Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, 65926 Frankfurt am Main, Germany.
8
Unité de Biologie Fonctionnelle et Adaptative (BFA), CNRS UMR 8251, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris, France; Institut de biologie intégrative de la cellule (I2BC), CNRS UMR 9198, Université Paris-Sud, Université Paris-Saclay, 91190 Gif-sur-Yvette, France.
9
Vital-IT Group, SIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
10
Cardiometabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, 88400 Biberach (Riss), Germany.
11
Vital-IT Group, SIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland. Electronic address: mark.ibberson@sib.swiss.
12
Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland. Electronic address: bernard.thorens@unil.ch.

Abstract

Plasma metabolite concentrations reflect the activity of tissue metabolic pathways and their quantitative determination may be informative about pathogenic conditions. We searched for plasma lipid species whose concentrations correlate with various parameters of glucose homeostasis and susceptibility to type 2 diabetes (T2D). Shotgun lipidomic analysis of the plasma of mice from different genetic backgrounds, which develop a pre-diabetic state at different rates when metabolically stressed, led to the identification of a group of sphingolipids correlated with glucose tolerance and insulin secretion. Quantitative analysis of these and closely related lipids in the plasma of individuals from two population-based prospective cohorts revealed that specific long-chain fatty-acid-containing dihydroceramides were significantly elevated in the plasma of individuals who will progress to diabetes up to 9 years before disease onset. These lipids may serve as early biomarkers of, and help identify, metabolic deregulation in the pathogenesis of T2D.

KEYWORDS:

T2D; biomarkers; ceramides; diabetes; dihydroceramides; glucose intolerance; high-fat diet; human; insulin sensitivity; lipidomics; metabolic challenge; mouse; prognostic; prospective cohort

PMID:
28249170
DOI:
10.1016/j.celrep.2017.02.019
[Indexed for MEDLINE]
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