The antihyperlipidemic effect of Fu-Ling-Pi is associated with abnormal fatty acid metabolism as assessed by UPLC-HDMS-based lipidomics

The surface layer of Poria cocos (SLPC), a traditional Chinese medicine, has been commonly used for diuretic and antihyperlipidemia in Asia. In order to understand its biochemical mechanism of antihyperlipidemia, a lipidomic approach based on ultra-performance liquid chromatography coupled with a quadrupole time-of-flight synapt high-definition mass spectrometry was carried out to characterize the plasma lipid metabolic profile of the antihyperlipidemic effect of SLPC in rats fed with a high fat diet. Lipid metabolites with significant changes were characterized as potential biomarkers associated with the development of hyperlipidemia and antihyperlipidemia of SLPC using partial least-squares-discriminate analysis, heatmap display, correlation coefficient analysis and receiver-operating characteristic curves. The analysis of the biological pathway was performed with metabolomics pathway analysis (MetPA). The lipid metabolic profile of hyperlipidemia rats separated from control rats and SLPC treated rats was closer to the control rats. Six lipid metabolites including the five fatty acyl lipids palmitic acid, dodecanoic acid, L-palmitoylcarnitine, oleoylcarnitine and linoleyl carnitine and one sphingolipid phytosphingosine were considered as biomarkers of diet-induced hyperlipidemia and antihyperlipidemic effect of SLPC. MetPA revealed that the identified lipid biomarkers were responsible for diet-induced hyperlipidemia and antihyperlipidemic effect of SLPC. These biomarkers were associated with fatty acid metabolism, fatty acid biosynthesis, sphingolipid metabolism, fatty acid elongation in mitochondria and unsaturated fatty acids biosynthesis. The findings suggest that a high fat diet led to the perturbation of fatty acid metabolism and sphingolipid metabolism, which may be the pharmacological basis of an antihyperlipidemic effect of SLPC.