Plasma Dihydroceramides Are Diabetes Susceptibility Biomarker Candidates in Mice and Humans

Publication date: 28 February 2017
Source:Cell Reports, Volume 18, Issue 9
Author(s): Leonore Wigger, Céline Cruciani-Guglielmacci, Anthony Nicolas, Jessica Denom, Neïké Fernandez, Frédéric Fumeron, Pedro Marques-Vidal, Alain Ktorza, Werner Kramer, Anke Schulte, Hervé Le Stunff, Robin Liechti, Ioannis Xenarios, Peter Vollenweider, Gérard Waeber, Ingo Uphues, Ronan Roussel, Christophe Magnan, Mark Ibberson, Bernard Thorens
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.

Graphical abstract

Teaser

Wigger et al. find that several sphingolipids in mouse plasma correlate with glucose tolerance and insulin secretion. Quantitative analysis of these and closely related lipids in human plasma from two cohorts reveal that dihydroceramides are significantly elevated in individuals progressing to diabetes, up to 9 years before disease onset.


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