Effect Of Diet And Genotype On The Lipidome Of Plasma, Liver And Aorta Of Mice With Altered Lipoprotein Metabolism

The impact of PCSK9 and LDLR on plasma cholesterol levels is well known, but their effect on the entire lipidome is lacking. This issue is relevant, since several lipid species, circulating at very low concentrations, can impair lipid metabolism and promote atherosclerosis development.
This study characterized and compared plasma, liver and aorta lipidomes of i) wild-type, ii) hypercholesterolemic Ldlr-KO and iii) hypocholesterolemic Pcsk9-KO mice fed a standard chow or a Western-type diet up to 30 and 16 weeks of age, respectively.
42 lipid species including cholesterol, cholesteryl esters, several sphingolipids, phospholipids and lysophospholipids, accumulated uniquely in the atherosclerotic aorta of Western-type diet-fed Ldlr-KO mice. In addition, multiple organ/tissue comparisons allowed to identify 16 lipids whose plasma and hepatic patterns mirrored the lipidome of the atherosclerotic aorta. These lipid species, belonging to cholesteryl esters, glucosyl/galactosylceramide, lactosylceramide, globotriaosylceramide, sphingomyelin and phosphatidylcholine could be further investigated as circulating biomarkers or therapeutic targets.