Modulation of hepatic lipidome by rhodioloside in high-fat diet fed apolipoprotein E knockout mice

Background: Rhodioloside is a glucoside of tyrosol isolated from Rhodiola rosea. However, its regulating effect on hepatic dyslipidemia of atherogenic mice has rarely been studied. Purpose: The specific aims of current study included to clarify lipidomic perturbation in liver tissues of apolipoprotein E deficient (apoE(-/-)) mice fed with high-fat diet, and to examine the effects of rhodioloside against atherosclerosis and dyslipidemia. Study Design: The comparisons of hepatic lipidome were executed between wide type (WT) mice fed with normal diet (NDC) and apoE(-/-) mice fed with high-fat diet (Model), WT mice fed with high-fat diet (HFDC) versus the model mice, as well as the model mice versus rhodioloside-treated atherosclerotic mice. Methods: Ultra high performance liquid chromatography coupled with a Q exactive hybrid quadrupole-orbitrap mass spectrometry (UPLC-MS/MS) was employed to provide an unbiased and simultaneous measurement of individual lipid species in liver tissues. Results: Multivariate statistical analysis derived from LC-MS spectra revealed that high-fat diet and apoE deficiency caused a series of disturbances on glyerolipid metabolism, glycerophospholipid metabolism and sphingolipid metabolism. Rhodioloside administration showed atheroprotective effects on the apoE(-/-) mice with regulating the levels of 1 phosphatidylcholine, 2 phosphatidylserines, 5 alkyldiacylglycerols and 3 alkenyldiacylglycerols back to normal. In particular, PC (4:0/15:0) was positively associated with high-density lipoprotein cholesterol in blood, both of which could be ameliorated by rhodioloside. Conclusion: Our results identified the abnormal hepatic lipids in atherosclerosis progression that could efficiently improved by rhodioloside. These lipids contributed to biological understanding of atherogenic dyslipidemia in liver and could also served as sensitive indicators for drug target screening.