Effect of hesperetin, a citrus flavonoid, on the liver triacylglycerol content and phosphatidate phosphohydrolase activity in orotic acid-fed rats.

The effect of dietary hesperetin on the hepatic lipid content and the enzyme activities involved in triacylglycerol (TG) synthesis in rats fed diets with or without 1% orotic acid (OA) was studied. Hepatic TG content was raised by approximately 5-fold after administration of OA for 10 days. The OA-feeding significantly increased the activity of hepatic microsomal phosphatidate phosphohydrolase (PAP), which is the rate-limiting enzyme for TG synthesis. Hepatic glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme activities were also increased. An addition of 1% hesperetin to the OA-supplemented diet resulted in the decrease of the hepatic TG content by 44% and of microsomal PAP activity. Dietary hesperetin alone neither affected liver TG content nor PAP activity significantly. OA-feeding caused an increased liver cholesterol level, whereas simultaneous addition of hesperetin and OA reduced its content to the control level. A slight reduction of hepatic cholesterol by hesperetin was also observed in the OA-free dietary group. The present study demonstrated that dietary hesperetin can reduce the hepatic TG accumulation induced by OA, and this was associated with the reduced activity of TG synthetic enzyme, PAP.

Effects of conjugated linoleic acid on serum leptin concentration, body-fat accumulation, and beta-oxidation of fatty acid in OLETF rats.

We investigated the efficacy of a 4-wk supplementation of conjugated linoleic acid (CLA) as free fatty acid (FFA) or triacylglycerol (TG) on serum leptin concentration, body-fat accumulation, and mitochondrial beta-oxidation in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. A significant reduction of serum leptin concentration (42%) and a decrease in the wet weights of perirenal, epididymal, and omental/visceral-adipose tissue in TG-CLA and FFA-CLA groups were found in comparison with the OLETF control group. Both forms of CLA supplementation produced a 5.2% decrease in body weight compared with the control even though food intake was similar in the OLETF groups. Moreover, both forms of CLA enhanced carnitine-palmitoyltransferase activity in brown adipose tissue, perirenal adipose tissue, red gastrocnemius muscle, and liver in comparison with the OLETF control group. Serum concentrations of non-esterified fatty acid and TG also were reduced in rats fed diets supplemented with TG-CLA and FFA-CLA.

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.

Inhibitory effects of oren-gedoku-to and its components on cholesteryl ester synthesis in cultured human hepatocyte HepG2 cells: evidence from the cultured HepG2 cells and in vitro assay of ACAT.

The pharmacological effects of Oren-gedoku-to (OGT), a Japanese-Chinese traditional herbal medicinal mixture on lipid biosynthesis were investigated in cultured human hepatocyte HepG2 cells. The addition of OGT (0.5 and 4.2 mg/ml), which had no effect on cell proliferation and cellular protein content, caused a marked decrease in the cellular cholesterol content, particularly cholesteryl ester content following 24 h incubation. The incorporation of 14C-oleate into cellular cholesteryl ester fraction was also reduced remarkably during incubation for 6 and 24 h. The effects of OGT, its components and its main active chemicals on acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity were studied in vitro to explore the mechanism by which OGT inhibits cholesteryl ester formation. The data confirmed that OGT, in a dose-dependent manner, and its components (Scutellaria baicalensis, Coptis japonica, Gardenia jasminoides and Phellodendron amurense) remarkably inhibit ACAT activity. Among the main active chemicals of OGT, baicalein, a kind of flavonoid, decreased ACAT activity in a dose-dependent fashion from the level of 10(-6)M. These results strongly suggest that OGT reduces the cholesteryl ester formation in human hepatocytes by inhibiting ACAT, and that baicalein may, in part, be responsible for ACAT inhibition.

Pharmacological effects of dai-saiko-to on lipid biosynthesis in cultured human hepatocyte HepG2 cells.

The pharmacological effects of Dai-saiko-to, a Japanese and Chinese traditional medicinal mixture (Kampohozai), on lipid biosynthesis were investigated in cultured human hepatocyte HepG2 cells. The addition of Dai-saiko-to (0.5 mg/ml), which had no significant effect on cell proliferation, caused a marked decrease in the intracellular triglyceride content with no significant changes in the other lipid fraction. At the same time, the incorporation of 14C-acetate or 3H-glycerol into the triglyceride or diglyceride fractions also decreased significantly. These results suggest that Dai-saiko-to decreases hepatic triglyceride biosynthesis, which might contribute to a reduction in plasma VLDL levels.

Dietary modifications of the biliary bile acid glycine:taurine ratio and activity of hepatic bile acid-CoA:amino acid N-acyltransferase (EC 2.3.1) in the rat.

Effects of dietary manipulations on the biliary bile acid glycine:taurine (G:T) ratio and the activity of hepatic bile acid-CoA:amino acid N-acyltransferase (EC 2.3.1) in the post-mitochondrial fraction of liver homogenates were examined in the rat. The G:T ratio in rats fed on the diet containing 100 g pectin/kg (2.18) was markedly higher than that in the animals fed on the diet containing 100 g cellulose/kg (0.09). The diets containing either 10 g cholesterol/kg or 5 g sodium cholate/kg, especially the latter, also increased the G:T ratio (0.77 and 2.33 respectively) compared with a control diet free of these steroids (0.34). When the saturating concentrations of taurine (20 mM) and glycine (100 mM) were the substrates, dietary pectin relative to cellulose significantly increased the activity of both taurine- and glycine-dependent bile acid-CoA:amino acid N-acyltransferase, but neither dietary bile acid nor cholesterol influenced it. In spite of the marked difference in the G:T ratio among the rats given various types of experimental diet, the bile acid-CoA:amino acid N-acyltransferase reaction produced taurine-but little glycone-conjugated bile acid when both taurine and glycine coexisted at physiological concentration ranges in the assay media. Dietary manipulations modified the hepatic taurine concentrations and the changes were inversely correlated with those in the G:T ratio. However, hepatic concentration of taurine (1.67-4.82 mumol/g) in rats given various types of experimental diet was comparable with or even higher than the reported Michaelis constant (Km) value of N-acyltransferase for this compound (0.8-2.5 mM).(ABSTRACT TRUNCATED AT 250 WORDS)

Smoking and health: a review prepared by the Smoking and Health Subcommittee of the Tobacco Industries Council, a council formed by the Minister of Finance of Japan.

Any definition of health is inevitably broad and contains various elements that may differ from one individual to another. Recent studies on the effects of smoking on physical and mental health have progressed remarkably and have great value in the fields of epidemiology, pathology, clinical medicine, and psychiatry. This report concludes that while smoking may have beneficial psychological effects on smokers, it may pose a risk to physical health.