In Situ Lipidomic Analysis of Nonalcoholic Fatty Liver by Cluster TOF-SIMS Imaging

Abstract

Mass spectrometry imaging has been used to map liver biopsies of several patients suffering from nonalcoholic fatty liver disease. This steatosis is characterized by an accumulation of triacylglycerols and diacylglycerols in the liver. Using time-of-flight-secondary ion mass spectrometry (TOF-SIMS) with a bismuth cluster ion source, it has been possible to map lipids in situ at the micrometer scale and to simultaneously characterize their molecular distribution on liver sections. Accumulation of triacylglycerols, diacylglycerols, monoacylglycerols, fatty acids, with the apparition of myristic acid, together with a dramatic depletion of vitamin E and a selective macrovacuolar localization of cholesterol are observed in steatosis areas of fatty livers compared to control livers. These ion species are concentrated in small vesicles having a size of a few micrometers. Moreover, very fine differences in lipid localizations, depending on alkyl acid chain lengths of diacylglycerols and fatty acids, have been found after careful scrutiny of the ion images. Finally, TOF-SIMS has revealed lipid zonation in the normal human liver and accumulation of very similar lipids to those detected in areas of the fatty livers, which are not characterized as steatotic ones by the histological control performed on serial tissue sections.

Lipidomic analysis of lipid droplets from murine hepatocytes reveals distinct signatures for nutritional stress

“…There are few other lipidomic studies on assessment of NAFLD. By Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS) imaging in thin sections of steatotic livers from patients, main DG and TG species were detected similar to our LC-MS/MS data ( 34 ). Based on a lipidomic approach and a mouse model similar to ours, it was reported that steatotic liver contains particularly enhanced metabolically linked DG and PC species ( 7 ).…”

The location and behavior of α‐tocopherol in membranes

“…This technique has already been used to image tocopherol location in cells [102] and tissues [103][104][105]. It would be fascinating if someone should now apply the tools of lipidomics to collecting data not only on the location of tocopherol, but also the phospholipid profile at the same location.…”

Time-of-flight secondary ion mass spectrometry imaging demonstrates the specific localization of deca-bromo-diphenyl-ether residues in the ovaries and adrenal glands of exposed rats

“…This method now enables drawing from various kinds of samples the density map (image) of any ion present in the mass spectra, with a spatial resolution from a few m to less than 500 nm, and with a mass range which is now reaching more than 1000 Da. In recent years, many applications of TOF-SIMS imaging have been published in the fields of biology and medicine [32][33][34][35][36][37][38][39][40][41][42][43]. However, it has never been directly applied to the exploration of persistent organic pollutants such as environmental or food contaminants.…”