Identification of a susceptible animal model and lipid biomarkers

Selection of an animal model with rapid development of liver steatosis (the "fatty liver disease" model) is correlated with profiling of triglyceride biomarkers

A collection of liver specimens were sampled from mice with distinct genetic backgrounds.

After only 15 days of "stressing" diet the animal genetic subgroups are scored by histology as "resistant" or "susceptible" to hepatosteatosis. The comparison of molecular species comprised in triglycerides (figure 1 below) by appropriate LC-MS2 methods points to a wide difference.

Statistical testing of the lipidomic profiles give an insight on differences appearing between the liver triglyceride composition. While mass spectrometry analysis detects more than 80 molecular species of liver triglyceridesonly a few specific triglyceride biomarkers have emerged in mice with a susceptible strain.

Accelerated de novo lipidogenesis explains the accretion of triglycerides in fatty liver. But only a few molecular species resulting of the interconversion of polyunsaturated fatty acid have the significance of PREDICTIVE BIOMARKERS for RESISTANCE/SUSCEPTIBILITY.

Figure below: The principal component analysis of the triglyceride composition shows the separation of a subgroup of mice with a high susceptibility to liver steatosis (identified by dark blue labels S1-S2). The cluster in the lower left quadrant of the biplot is explained by a particular composition of triglyceride molecular species. Tandem mass spectrometry identifies the accumulation of polyunsaturated enriched triglycerides (labeled as a 8 letters code) as the PREDICTIVE BIOMARKERS.



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