Lipid-lowering Effects And Molecular Mechanisms Of Fucoidan From The Seaweed Laminaria Japonaria In Apolipoprotein E-deficient Mice

Effective lipid-lowering treatment can reduce its morbidity and mortality.At present,accumulating data indicated that the synthesized and commercially available drugs,such as statins and fibrates,have side effects.Fucoidan(FUC)is a kind of highly sulfated polysaccharide,which is widely used in medical field because of its various biological activities.This study was designed to investigate the anti-atherosclerosis effect of the fucoidan from widely consumed brown seaweed Laminaria japonica(LFUC),and especially its underlying mechanisms of action.Twenty apoE-/-mice(10-11 weeks old,23±2 g)were purchased from Beijing HFK Bioscience Co.,Ltd.Mice were fed a high-fat diet.After acclimatization for 1 week,the mice were randomly divided into the model group,the LXR agonist group,the low-dose LFUC group and the high-dose LFUC group.Mice were weighted and plasma was sampled after overnight fasting.The plasma total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),apolipoprotein A1(apoA1),apolipoprotein B(apoB),nonesterified fatty acid(NEFA),lipoprotein lipase(LPL),alanine transaminase(ALT)and aspartate transaminase(AST)levels were measured using an automatic biochemical analyzer HITACHI Labospect 008AS.The aortic root sections were stained with Oil red O for histopathological analysis.Western blotting(WB)and real-time fluorescence quantitative PCR(RT-PCR)were used to detect the effects of LFUC on the expression of RCT(Reverse cholesterol transport)-related proteins and genes in liver and small intestine.Our results demonstrated that LFUC significantly attenuated atherosclerotic lesion and hyperlipidemia in a dose-dependent manner in apolipoprotein E-deficient(apoE-/-)mice fed a high-fat diet.Moreover,LFUC significantly decreased lipid deposition and increased the expression of scavenger receptor B type 1(SR-B 1),peroxisome proliferator-activated receptor(PPAR)α and∞,liver X receptors(LXR)and ATP-binding cassette transporter(ABC)transporters in the liver of the apoE-/-mice.Furthermore,LFUC significantly improved the expression of ABCG8 and reduced the expression of Niemann-Pick Cl-like 1(NPC1L1)in the small intestine of the apoE-/-mice.These results demonstrated that LFUC attenuates hyperlipidemia and atherosclerosis may partially by modulating RCT-related genes and proteins expression in apoE-/-mice.1),LFUC increased the lipid transfer from plasma to the liver by up-regulating SR-B1;2),it accelerated lipid metabolism in the liver by up-regulation of PPARα and β;3)it increased cholesterol excretion by up-regulating LXR/ABC transporters and decreased cholesterol absorption by down-regulating NPC1L1 in the small intestine.