Effect Of Niacin On The Gene Expressions Of Reverse Cholesterol Transport In Adipocytes And Its Mechanism Research

Background Atherosclerosis is one of the main diseases that harms to health of human beings. It is also the major causes of morbidity and mortality in patients with cardiovascular disease. Adipose tissue is the biggest energy storage organs, also is the largest free cholesterol "storage tank" in the body and takes part in the buffer role of the blood circulatory cholesterol metabolism. Adipocyte is in the form of triglyceride to main function of energy storage, and the metabolism of cholesterol efflux is great significative for maintaining cholesterol balance. Many transport bodys participate in cholesterol efflux, such as ATP-binding cassette transporter Al(ABCA1) which belongs a subtype of ATP binding cassette transporter genes in the family and takes participate in reverse cholesterol transportation and the initial step of HDL generation. Scavenger receptor B type I(SR-BI) is a receptor of high density lipoprotein (HDL), which can mediate selective absorption of cholesterol ester(CE). Caveolin-1(CAV-1) is a protein which maintains structure skeleton of caveolae. It is combined with the function of cholesterol carrier and promotes cholesterol efflux which plays an important regulatory role for maintaining normal cholesterol steady in the body. Cholesterol efflux may by the above transport bodys in adipocyte and increases plasma of HDL, involved in the cholesterol Reverse transportation(RCT), thus has the important role for anti-atherosclerosis.However, despite widespread use of statin therapy, residual cardiovascular risk remains. Therefore, it becomes one of tactics of anti-atherosclerosis treatment for us to keep looking for the auxiliary medicine which can optimize lipid profiles and reduce risk further. Niacin has got a lot of attentions because of its comprehensive and unique effect on lowering lipid and increasing HDL-C. Recent studies found that the "old drug" has an obvious anti-atherogenic effect and also can significantly reduce the incidence and mortality of coronary heart disease. The mechanism of anti-atherogenic effect of niacin so far hasn’t been completely confirmed yet. Apart from being related with pleiotropic role of niacin in lipid-lowering, but whether can take participation in this effect of RCT in adipose tissue or adipocytes, which is still being studied.Objective To investigate the effects of niacin on serum lipid levels and expressions of ABCA1、SR-BI and CAV-1in adipose tissue from experimental atherosclerosis rabbits, and the direct effect of niacin on ABCA1、SR-BI and CAV-1mRNA expression in primary rabbit adipocytes. More, we discusse the mutual relationship between ABCA1and CAV-1mRNA expression and clarify the effect of niacin on reverse cholesterol transport and its mechanism.Methods Sixteen New Zealand white rabbits were fed with high-fat diet for eight weeks, and then randomly divided into two groups:①hyperlipidemia group(n=8):maintained on high fat diet for six weeks;②niacin treatment group(n=8):the same fat diet plus niacin [200mg/(kg·d)] for six weeks. Control group (n=8) was fed with normal diet for fourteen weeks. We measured the blood lipid level and body weight before and at the the end of8th and14th week of experiment. At the end of the experiment, the rabbits were killed for taking out groin subcutaneous adipose tissue which saved in liquid nitrogen. In addition, we observe the direct effects of niacin on ABCAl、SR-BI and CAV-1mRNA expression in primary rabbit adipocytes was assayed, and the effects of niacin on ABCA1and CAV-1mRNA expression in primary rabbit adipocytes which are blocked by filipin. Then, the expressions of ABCA1、SR-BI and CAV-1in adipose tissue and adipoytes were detected by real-time fluorescence quantitative polymerase chain reaction (FQ-PCR).Results Compared with control group, the levels of total cholesterol, triglyceride and LDL-cholesterol of hyperlipaemia group were significantly increased(P<0.01), and the lower expressions of ABCA1、SR-BI mRNA(P <0.05)and CAV-1mRNA(.P<0.01); Compared with hyperlipaemia group, levels of total cholesterol, triglyceride and LDL-cholesterol of niacin group were reduced significantly(P<0.01), while HDL-Cholesterol was obviously increased (P<0.01), more expressions of ABCA1and CAV-1mRNA(P<0.01), but the effect of niacin on expression of SR-BI mRNA was not significant (P>0.05). Niacin could increase ABCA1and CAV-1mRNA expression in primary rabbit adipocytes(P<0.01), but had no effect on SR-BI mRNA expression(P>0.05). After filipin blocking, expressions of ABCA1and CAV-1mRNA are significantly reduced(P<0.05), but niacin could significantly increase ABCA1and CAV-1mRNA expression(P<0.05). Correlation analysis suggested that expression of ABCA1mRNA was positively correlated with expression of CAV-1mRNA(r=0.963, P=0.00).Conclusion ABCA1、SR-BI and CAV-1are highly expressed in adipocytes; Niacin can significantly improve the lipid profile and up-regulate ABCA1and CAV-1mRNA expression in adipocytes and adipose tissue, but has nothing with SR-BI mRNA expression; Niacin may regulate ABCA1mRNA expression via CAV-1gene.