Article

Lipid mapping of colonic mucosa by cluster TOF-SIMS imaging and multivariate analysis in cftr knockout mice.

Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, Gif-sur-Yvette, France.
The Journal of Lipid Research (impact factor: 5.56). 10/2010; 51(10):3034-45. DOI:10.1194/jlr.M008870
Source: PubMed

ABSTRACT The cftr knockout mouse model of cystic fibrosis (CF) shows intestinal obstruction; malabsorption and inflammation; and a fatty acid imbalance in intestinal mucosa. We performed a lipid mapping of colon sections from CF and control (WT) mice by cluster time of flight secondary-ion mass spectrometry (TOF-SIMS) imaging to localize lipid alterations. Data were processed either manually or by multivariate statistical methods. TOF-SIMS analysis showed a particular localization for cholesteryl sulfate at the epithelial border, C16:1 fatty acid in Lieberkühn glands, and C18:0 fatty acid in lamina propria and submucosa. Significant increases in vitamin E (vE) and C16:0 fatty acid in the epithelial border of CF colon were detected. Principal component analysis (PCA) and partitioning clustering allowed us to characterize different structural regions of colonic mucosa according to variations in C14:0, C16:0, C16:1, C18:0, C18:1, C18:2, C20:3, C20:4, and C22:6 fatty acids; phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol glycerolipids; cholesterol; vitamin E; and cholesteryl sulfate. PCA on spectra from Lieberkühn glands led to separation of CF and WT individuals. This study shows for the first time the spatial distribution of lipids in colonic mucosa and suggests TOF-SIMS plus multivariate analyses as a powerful tool to investigate disease-related tissue spatial lipid signatures.

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Keywords

cftr knockout mouse model
 
cluster time
 
colonic mucosa
 
different structural regions
 
epithelial border
 
fatty acid imbalance
 
flight secondary-ion mass spectrometry
 
intestinal mucosa
 
intestinal obstruction
 
lamina propria
 
localize lipid alterations
 
multivariate analyses
 
multivariate statistical methods
 
partitioning clustering
 
phosphatidylinositol glycerolipids
 
powerful tool
 
Principal component analysis
 
Significant increases
 
vitamin E
 
WT individuals