Hypocholesterolemic effect based on molecular structure and gene expression

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First of all, I established RT-PCR method for estimation of hepatic mRNA expression of various proteins involved in lipid metabolism, by using densitograph AE-6915 and lane analyzer system (Atto Corp.Tokyo). The established proteins are apoA-I, apoC-II, apoC-III, apoE, acyl-CoA oxidase (ACO), cholesterol 7 α -hydroxylase, HMG-CoA reductase, microsomal triglyceride transferprotein (MTP), h-TGL, peroxisome proliferator-activated receptor (PPAR) α, acyl-CoA oxidase (ACO) fatty acid synthase (FAS), acyl-CoA synthetase (ACS) and uncoupling protein-2 (UCP-2).Next, I applied the RT-PCR method to elucidation of the lipid-regulating activity of Kabosu-juice residue, quinoa powder and natural oils such as harpseal oil, soybean oil and rapeseed oil, using spontaneously hypertensive rats (SHR) as an animal model.In the Kabosu-juice residue experiment, serum lipids of the experimental group were significantly decreased, which was due to decreases in all lipoprotein fractions. Serum apoA-I, apoA-IV … More and apoE were also significantly decreased, which was mainly due to decreases in the high-density lipoprotein (HDL) fraction. In addition, hepatic apoA-I mRNA expression of the experimental group was markedly decreased.In the natural oil experiment, serum HDL-cholesterol and apoA-I of rapeseed oil group increased significantly compared with the other groups (soybean and harpseal oils), while hepatic apoA-I mRNA expression remained unchanged. In the contrast, serum lipids of harpseal oil group rich in n-3 polyunsaturated fatty acids (PUFA) including DPA (Docosapentaenoic acid) decreased obviously compared with the other groups, which was mostly due to decreases in the all lipoprotein fractions. These changes were associated with significant decreases in serum apoA-I, apoB and hepatic apoA-I mRNA expression, suggesting that harpseal oil may decrease very low-density lipoprotein (VLDL), low-density llipoprotein (LDL) and apoA-I HDL.These effects of harpseal oil may be attributed to n-3 PUFA including DPA.However, it is difficult to discriminate the physiological function of DPA from that of the other n-3 PUFA.On the one hand, anti-oxidative activity of the LDL fraction was significantly low only in the rapeseed group, suggesting that LDL fraction of rapeseed oil group may be less resistant to oxidation.These two experiments indicate that the hypocholesterolemic effect of Kabosu-juice residue and harpseal oil may be mediated by PPAR α. Less