Effects of dietary alpha-linolenic, eicosapentaenoic and docosahexaenoic acids on hepatic lipogenesis and beta-oxidation in rats.

The effects of dietary alpha-linolenic, eicosapentaenoic and docosahexaenoic acids on the enzyme activities related to hepatic lipogenesis and beta-oxidation were compared under constant polyunsaturated/monounsaturated/saturated fatty acids and n-6/n-3 ratios of dietary fats in rats. Dietary fat containing linoleic acid as the sole polyunsaturated fatty acid (PUFA) was also given as a control. The concentration of serum triglyceride and phospholipid in the three n-3 PUFA groups was lower than in the linoleic acid group. The hepatic triglyceride concentration was lower and the phospholipid concentration was higher in the three n-3 PUFA groups than in the linoleic acid group. Cytosolic fatty acid synthase (FAS) activity was lower in the n-3 PUFA groups than in the linoleic acid group, the reduction being more predominant in the eicosapentaenoic acid and docosahexaenoic acid groups than in the alpha-linolenic acid group. The cytosolic activities of the NADPH-generating enzymes, glucose-6-phosphate dehydrogenase (G6PDH) and the malic enzyme, were lower in the three n-3 PUFA groups. The activity of carnitine palmitoyltransferase (CPT) in mitochondria was higher only in the eicosapentaenoic acid group than in the other groups. The activity of Mg(2+)-dependent phosphatidate phosphohydrolase (PAP) in microsomes and cytosol was lower in the eicosapentaenoic and docosahexaenoic acid groups than in the linoleic acid group, while there was no effect of dietary fats on the activities of diacylglycerol acyltransferase (DGAT) and glycerol-3-phosphate acyltransferase (G3PAT) in microsomes. The CTP: phosphocholine cytidylyltransferase (CT) activity in the homogenate was lower in the n-3 PUFA groups, the reduction being more prominent in the eicosapentaenoic and docosahexaenoic acid groups than in the alpha-linolenic acid group. The choline kinase (CK) activity in cytosol was lower in the eicosapentaenoic acid group than in the linoleic acid group. These results showed that dietary alpha-linolenic, eicosapentaenoic and docosahexaenoic acids differently influenced hepatic lipogenesis and the partition of fatty acid into oxidation or glycerolipid synthesis.

Association between hepatic triacylglycerol accumulation induced by administering orotic acid and enhanced phosphatidate phosphohydrolase activity in rats.

Orotic acid is known to cause fatty liver, but it is unclear whether this is caused partly by stimulation of the enzymes for triacylglycerol (TG) synthesis. To understand the change of hepatic TG metabolism in fatty liver induced by orotic acid, we determined the liver tissue TG level and phosphatidate phosphohydrolase (PAP) activity over time in rats fed on a diet containing orotic acid (OA). A dietary lipid content of 10% was achieved by using n-6 fatty acid-rich corn oil in experiment 1, and n-6 fatty acid-rich safflower oil (SO) and n-3 fatty acid-rich fish oil (FO) with the same polyunsaturated fatty acid/monounsaturated fatty acid/saturated fatty acid (P/M/S) ratio in experiment 2. In experiment 1, an increase in the hepatic TG level due to OA intake was observed from day 5 onwards, the level rising approximately 6-fold by day 10. The activity of hepatic microsomal PAP, the rate-limiting enzyme in TG synthesis, increased markedly from day 5 onwards, concurrent with the liver diacylglycerol concentration. A strong correlation (r = 0.974) was observed between the hepatic TG level and microsome-bound PAP activity. In experiment 2, we investigated the effects of dietary fatty acid on OA-induced fatty liver. Compared with the n-6 fatty acid-rich vegetable oil diet, the relative increase in hepatic TG was smaller with the n-3 fatty acid-rich FO diet, and hepatic PAP activity fell markedly to the level for an OA-free diet. In addition, the hepatic TG accumulation and serum TG concentration were lower in the FO group than in the SO group. Nevertheless, because the hepatic TG level was low, it seems that the inhibition of liver PAP activity by FO possibly had a strong influence on the accumulation of TG in the liver. In conclusion, enhanced TG synthesis mediated by changes in liver PAP activity was involved in the hepatic TG accumulation induced by OA administration, this change being markedly suppressed by dietary n-3 fatty acids.