Objective: Used low density lipoprotein receptor knockout(LDLR KO) hamster as the model similar to human dyslipidemia to observe the lipid-lowering effect of equol on heterozygotes.
Methods: With soy-free high cholesterol high fat diet, 12-week-old LDLR KO female heterozygous hamsters were randomly divided into negative control group(no addition), positive control group(add 0.004% ezetimibe), genistein group(add 0.1%), and low, medium and high-dose groups of equol(add 0.025%, 0.05%, 0.1% respectively). Body weight, food consumption and blood lipid were continuously monitored for 12 weeks after feeding each group. Finally, liver morphology and lipid metabolism related genes expressions were checked.
Results: There was no significant difference in body weight and average weekly food intake among the groups. The blood lipids in negative control group increased over time, and the cholesterol and triglyceride levels of LDLR KO heterozygous hamsters were significantly reduced by ezetimibe in the second week, while the high-density lipoprotein cholesterol was also significantly decreased. The lipid-lowering effects of genistein and equol were weaker than ezetimibe, and there was significant difference between the two groups after 12 weeks, but the decrease of HDL-c was not as significant as ezetimibe. Compared with genistein, the effect of medium and high dose equol was stronger. At 12 weeks, the liver weight ratio also decreased significantly, and the liver lipid accumulation was inhibited, especially in the high dose of equol. The expression of ApoAI, SREBP-2 and HMGCR were significantly up-regulated by equol and genistein.
Conclusion: Equol could reduce female LDLR KO hamster blood lipid. It may play a role in lipid lowering by inhibiting cholesterol absorption besides estrogen receptor pathway, but it is weaker than NPC1 L1 inhibitor. At the same time, up-regulation of ApoAI inhibits the decrease of high-density lipoprotein and reduces lipid accumulation in liver.
Keywords: equol; ezetimibe; gene knockout hamster; genistein; lipid metabolism; low density lipoprotein receptor.