Dietary acetic acid reduces serum cholesterol and triacylglycerols in rats fed a cholesterol-rich diet

To investigate the efficacy of the intake of vinegar for prevention of hyperlipidaemia, we examined the effect of dietary acetic acid, the main component of vinegar, on serum lipid values in rats fed a diet containing 1 % (w/w) cholesterol. Animals were allowed free access to a diet containing no cholesterol, a diet containing 1 % cholesterol without acetic acid, or a diet containing 1 % cholesterol with 0.3 % (w/w) acetic acid for 19 d. Then, they were killed after food deprivation for 7 h. Cholesterol feeding increased serum total cholesterol and triacylglycerol levels. Compared with the cholesterol-fed group, the cholesterol and acetic acid-fed group had significantly lower values for serum total cholesterol and triacylglycerols, liver ATP citrate lyase (ATP-CL) activity, and liver 3-hydroxy-3-methylglutaryl-CoA content as well as liver mRNA levels of sterol regulatory element binding protein-1, ATP-CL and fatty acid synthase (P<0.05). Further, the serum secretin level, liver acyl-CoA oxidase expression, and faecal bile acid content were significantly higher in the cholesterol and acetic acid-fed group than in the cholesterol-fed group (P<0.05). However, acetic acid feeding affected neither the mRNA level nor activity of cholesterol 7alpha-hydroxylase. In conclusion, dietary acetic acid reduced serum total cholesterol and triacylglycerol: first due to the inhibition of lipogenesis in liver; second due to the increment in faecal bile acid excretion in rats fed a diet containing cholesterol.     

Pancreatic enzyme and plasma cholesterol response to chronic ingestion of a nonabsorbable lipid in rats

Pancreatic enzyme activity and plasma and high density lipoprotein (HDL) cholesterol levels were measured in rats chronically fed a nonabsorbable lipid, sucrose polyester (SPE), to determine if the rat pancreas responds to SPE as a dietary lipid or a nonnutritive ingredient. Adult male rats were fed for 28 d a diet containing either 5% or 20% corn oil, 5% SPE, 16% and 4% hydrogenated palm oil (HPO), or 16% corn oil and 4% HPO. HPO is used to prevent anal leakage of unabsorbed oil when SPE is fed at high dietary levels. Since HPO and SPE are not absorbed, rats fed SPE derive their energy from protein and carbohydrate in the diet. The tissue levels of pancreatic enzymes in rats consuming high levels of SPE in the diet resemble those of rats eating a low fat diet in which energy is derived from carbohydrate and protein. Plasma and HDL cholesterol levels were lowest in the group consuming high levels of SPE, an observation that is consistent with previous reports. These data indicate that the pancreas responds to SPE as a nonnutritive ingredient rather than a digestible dietary lipid.     

Dietary glycemic load assessed by food-frequency questionnaire in relation to plasma high-density-lipoprotein cholesterol and fasting plasma triacylglycerols in postmenopausal women

BACKGROUND: In metabolic studies, both greater carbohydrate intakes and higher glycemic indexes (GIs) raise fasting triacylglycerol concentrations. In epidemiologic studies, dietary glycemic load (GL) is positively associated with risk of coronary artery disease and type 2 diabetes. OBJECTIVE: We examined both the physiologic relevance of GI and GL and the ability of dietary questionnaires to measure these variables. DESIGN: In the Nurses' Health Study, we measured plasma triacylglycerol concentrations in fasting blood samples from 185 healthy postmenopausal women and HDL-cholesterol concentrations in an additional 95 nonfasting samples. Dietary carbohydrate, GI, and GL were assessed by use of semiquantitative food-frequency questionnaires. The cross-sectional associations between these 3 variables and plasma triacylglycerol and HDL were assessed, with adjustment for potential confounding factors. RESULTS: For the lowest and highest quintiles of GL, the multivariate-adjusted geometric mean triacylglycerol concentrations were 0.98 and 1.75 mmol/L (87 and 155 mg/dL; P for trend < 0.001). Both overall GI (P for trend = 0.03) and carbohydrate (P for trend < 0.01) contributed independently to the strong positive association between GL and fasting triacylglycerol concentrations. GL was also inversely associated with HDL-cholesterol concentrations. For the lowest and highest quintiles of GL, the mean HDL-cholesterol concentrations were 1.50 and 1.34 micromol/L (58 and 52 mg/dL; P for trend = 0.03). The relation between GL and fasting triacylglycerol concentrations differed significantly by body mass index (BMI; in kg/m(2)) categories (P < 0.001 for interaction). For the lowest to the highest quintiles of GL, the mean triacylglycerol concentrations were 0.92 and 2.24 mmol/L (81 and 198 mg/dL) in women with BMIs > 25 (P for trend < 0.001) and 1.02 and 1.42 mmol/L (90 and 126 mg/dL) in women with BMIs < or = 25 (P for trend < 0.001). CONCLUSION: These data support the physiologic relevance of the GL as a potential risk factor for coronary artery disease in free-living women, particularly those prone to insulin resistance. These findings also document the ability of a semiquantitative food-frequency questionnaire to assess dietary GIs and GLs.     

Effects of methyl-group acceptors on the regulation of plasma cholesterol level in rats fed high cholesterol diets

The effects of methyl-group acceptors such as glycine, guanidinoacetic acid, and nicotinamide on cholesterol metabolism and phosphatidylcholine(PC) biosynthesis were investigated with rats fed a 25% casein diet containing cholesterol with or without methionine supplement. The effect of ethanolamine, an indirect methyl-group acceptor via phosphatidylethanolamine(PE) formation, was also compared with those of methyl-group acceptors. The methyl-group acceptors and ethanolamine decreased or tended to decrease plasma total cholesterol level when added to the 25% casein diet. These compounds also significantly depressed the methionine-induced enhancement of plasma cholesterol level. The activity of PE N-methyltransferase was decreased by the addition of glycine, guanidinoacetic acid, and nicotinamide, but not ethanolamine, to the reaction mixture when assayed using the postmitochondrial fraction of liver homogenate, suggesting that PE N-methyltransferase activity can be depressed by glycine N-methyltransferase, guanidinoacetic acid N-methyltransferase, and nicotinamide N-methyltransferase systems. The PE N-methyltransferase activity in liver microsomes, however, did not decrease in response to the dietary addition of methyl-group acceptors. The in vitro incorporation of [CH3-14C]methionine into PC of liver slices was also significantly inhibited by the addition of glycine and nicotinamide, but not guanidinoacetic acid and ethanolamine, to the incubation medium. It is suggested that methyl-group acceptors can decrease plasma cholesterol level at least in part through the depression of PC biosynthesis via PE N-methylation pathway, and that the mechanism for the plasma cholesterol-lowering effect of ethanolamine is different from that of methyl-group acceptors.     

Effects of methionine and related compounds on plasma cholesterol level in rats fed a high cholesterol diet

The comparative effects of methionine and its structurally and metabolically related compounds on plasma cholesterol level were investigated with rats fed a high cholesterol diet. The plasma cholesterol level was significantly enhanced by the dietary addition of methyl compounds such as L-methionine, D-methionine, choline and betaine. On the other hand, the intermediary metabolites of methionine such as homocystine, cysteine and 3-methylthiopropionate reduced plasma cholesterol. S-Methyl-L-cysteine and dimethylglycine had no significant effect. The plasma cholesterol-elevating effects of methionine, betaine and histidine were all prevented, more or less, by the concurrent addition of glycine to the diet, suggesting the existence of a common mechanism for their effects. The results support a possibility that the plasma cholesterol-elevating efficacy of methionine is attributable to its methyl group.     

Effect of individual amino acids on plasma cholesterol level in rats fed a high cholesterol diet

The effect of individual amino acids added to a cholesterol containing casein diet on the plasma cholesterol level of rats was systematically investigated with objective of confirming the possibility that specific amino acids are responsible for the regulation of plasma cholesterol level by dietary proteins. Half the amino acids tested were effective to some degree in influencing the plasma cholesterol level when amino acids were added singly to the diet at a 5% level. However, only sulfur containing amino acids had significant effects when added to the diet at a 1% level; Met enhanced and Cys reduced the plasma cholesterol level. In addition, the results of an experiment with amino acid mixture diets with different Met, Cys, and/or Gly contents indicated the importance of sulfur amino acids and also of Gly in plasma cholesterol regulation. The results obtained here support the notion that the plasma cholesterol level of rats can be influenced by specific amino acids or amino acid compositions of dietary proteins, at least under the experimental conditions used.     

Naringin time-dependently lowers hepatic cholesterol biosynthesis and plasma cholesterol in rats fed high-fat and high-cholesterol diet

The flavonoid naringin was investigated for its differential effects on hepatic cholesterol regulation when supplemented for 3 weeks and 6 weeks. Sprague-Dawley rats were fed a high-fat and high-cholesterol diet with or without 0.02% naringin supplement for 3 or 6 weeks. Supplementation with naringin resulted in a significant decrease in the plasma cholesterol and triglyceride concentrations in the 6-week trial. Although high-density lipoprotein (HDL)-cholesterol was not altered in either trial, the HDL-cholesterol/total cholesterol ratio (in percent) was significantly higher, and the atherogenic index was significantly lower in the naringin-supplemented groups in the 6-week trial. The hepatic cholesterol content was also lowered by naringin supplementation only in the 6-week trial. The hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity was lower in the rats supplemented with naringin for 6 weeks, while the hepatic acyl-coenzyme A:cholesterol acyltransferase activity was lower in both the 3-week and 6-week trials. Results indicate that supplementation with naringin for 3 weeks did not exhibit a hypolipidemic effect when given with a HFHC diet. Naringin can, however, be beneficial for lowering hepatic cholesterol biosynthesis and levels of plasma lipids when supplemented for 6 weeks in this animal model.     

Effect of green tea catechins on plasma cholesterol level in cholesterol-fed rats

Effects of tea catechins (tannins) on lipid metabolism were studied in male weanling rats fed a 25% casein diet containing 15% lard and 1% cholesterol for 28 days. Crude tea catechins prepared from green tea powder were supplemented at a 1% and 2% of the lard-cholesterol diet. The addition of 2% tea catechins slightly depressed growth but at the 1% level was without effect. Tea catechins decreased plasma total cholesterol, cholesterol ester, total cholesterol--HDL-cholesterol (VIDL-+LDL-cholesterol) and atherogenic index (VLDL-+LDL-cholesterol/HDL-cholesterol). Hematocrit and plasma glucose were not altered by the addition of tea catechins. The liver weight, liver total lipids and cholesterol concentrations in rats fed the lard-cholesterol diet increased more than in the control rats, but the addition of tea catechins to the lard-cholesterol diet decreased those parameters. Tea catechin supplementation increased fecal excretion of total lipids and cholesterol. The results demonstrate that tea catechins exert a hypocholesterolemic effect in cholesterol-fed rats.     

Effect of excess dietary L-histidine on plasma cholesterol levels in weanling rats

Supplementation of a closed formula, cereal based stock diet with excess L-histidine at a 5% or 8% level for 4 days reduced growth and induced hepatomegaly and an increase in plasma cholesterole levels in weanling rats. The enlargement of the liver was in part due to glycogen accumulation; plasma glucose concentration was unchanged. Feeding four different amino acids (L-phenylalanine, L-glutamic acid, glycine and L-tryptophan), at levels which caused reduction of growth comparable to the 5% and 8% L-histidine supplementation, did not effect liver weight or plasma cholesterol levels. L-Threonine added, at a 2% level, to the 8% L-histidine diet did not alleviate any of the histidine effects. Rats fed a diet containing 5% urocanic acid, the first metabolite of the histidine degradative pathway, grew at a normal rate but had higher plasma cholesterol levels compared to rats fed stock diet. When rats fed L-histidine-or urocanic acid-supplemented diets were returned to stock diet, a normal growth rate was resumed immediately and plasma cholesterol levels returned to normal within 6 days. These results suggest that L-histidine and/or urocanic acid induce a hypercholesterolemia which disappears several days after the supplementation ceases.     

Effect of dietary cholesterol on hepatic lipogenesis and plasma insulin and free fatty acid levels in rats.

In order to further investigate the metabolic alterations in the liver of cholesterol-fed rats, the following parameters were determined: (a) the activities of hepatic glucose-6-phosphate dehydrogenase, NADP-malate dehydrogenase, citrate cleavage enzyme, acetyl CoC carboxylase, and fatty acid synthetase; (b) the rate of hepatic fatty acids synthesis in vivo or in vitro; and (c) the concentration of immunoreactive insulin, free fatty acids, and glucose in the plasma. The experimental diets usually contained 1.5% cholesterol and 0.5% cholic acid. Cholesterol feeding resulted in a three- to fourfold decrease in the activities of hepatic glucose-6-phosphate dehydrogenase, NADP-malate dehydrogenase, and citrate cleavage enzyme and up to a two-fold decrease in the activities of acetyl CoA carboxylase and fatty acid synthetase. The rate of fatty acid synthesis was not sifnigicantly decreased when rats were fed the cholesterol-supplemented diets for only 2 to 4 weeks, despite marked decreases in the activities of the lipogenic enzymes. But when cholesterol feeding was continued for periods longer than 5 weeks, there was a significant decrease in the rate of fatty acid synthesis in the liver. Cholesterol feeding decreased the levels of circulating insulin and elevated plasma free fatty acid levels. Plasma glucose levels were not significantly changed. Cholesterol feeding can result in a wide range of metabolic alterations. These metabolic alterations may have some impact on the development of hypercholesterolemic-related metabolic disorders.     

Hypocholesterolemic effect of triterpene alcohols with soysterol on plasma cholesterol in rats

To identify the synergistic hypocholesterolemic substance found in soybean oil unsaponifiable matter, rats were fed diets containing various fractions of the unsaponifiable matter prepared by silicic acid column chromatography. The plasma cholesterol level of the group fed the alcohol fraction, which mainly consisted of triterpene alcohols, was significantly lower and the effect was synergistic with soysterol. So the effect of cycloartenol and 24-methylenecycloartanol, which are main constituents of triterpene alcohols in soybean oil unsaponifiable matter, was investigated. Both compounds were prepared from gamma-oryzanol (ferulate) and were added (0.05%) respectively to the experimental diet containing 0.5% cholesterol and 1% soysterol. It was observed that both cycloartenol and 24-methylenecycloartanol in combination with soysterol greatly reduced the plasma cholesterol and enhanced cholesterol excretion. This suggests that the hypocholesterolemic activity of dietary vegetable oils may account for not only their fatty acid compositions and sterol contents but also the synergistic hypocholesterolemic effect of triterpene alcohols.     

Tartary buckwheat sprout powder lowers plasma cholesterol level in rats

We examined the effects of different types of buckwheat sprouts on the plasma cholesterol concentration, fecal steroid excretion and hepatic mRNA expression related to cholesterol metabolism in rats. Rats were fed a cholesterol-free diet with 5 g of Kitawasesoba common buckwheat sprout powder (KS)/100 g, 5 g of Hokkai T no. 8 tartary buckwheat sprout powder (HS-8)/100 g or 5 g of Hokkai T no. 9 tartary buckwheat sprout powder (HS-9)/100 g of diet for 4 wk. Control rats were fed a diet with alpha-cornstarch instead of sprout powder for 4 wk. There were no significant differences in food intake, body weight, liver weight or cecal contents among the groups. Plasma total cholesterol concentrations in the HS-8 and HS-9 groups were significantly lower than in the control group, whereas there was no significant difference between the KS and control groups. Fecal bile acid excretion and cecal short-chain fatty acid concentrations in the KS, HS-8 and HS-9 groups were significantly greater than in the control group. Furthermore, fecal matter excretion in the KS, HS-8 and HS-9 groups tended to be increased compared to the control group, with that in the HS-8 group being significantly higher than in the control group. Hepatic cholesterol 7alpha-hydroxylase mRNA expression in the KS, HS-8 and HS-9 groups and hepatic HMG-CoA reductase mRNA expression in the HS-9 group were significantly higher than in the control group. The results suggest that tartary buckwheat sprout powder has a serum cholesterol-lowering function by enhancing fecal bile acid excretion through increased fecal matter excretion or the upregulation of hepatic cholesterol 7alpha-hydroxylase mRNA expression in rats.     

Effect of dietary methionine on plasma and liver cholesterol concentrations in rats and expression of hepatic genes involved in cholesterol metabolism

Methionine has been shown to increase plasma cholesterol in animals. In the present study, mechanisms were investigated by which methionine could alter cholesterol metabolism. In the first experiment, forty growing rats were fed four casein-based diets differing in methionine content (2.6, 3.5, 4.5 or 6.0 g/kg) for 14 d. In the second experiment, isolated rat hepatocytes were incubated in media supplemented with 50, 100 or 200 micromol/l methionine. Dietary methionine tended to increase plasma homocysteine concentrations in the rats (P=0.058). A weak positive correlation between circulating homocysteine and plasma cholesterol was observed (R2 0.27, P<0.01). Rats fed 3.5 g/kg or more of methionine had higher concentrations of cholesterol in their plasma, in lipoprotein fractions of density (rho; kg/l) 1.0061.063, and in liver than rats fed 2.6 g/kg methionine. Rats fed 6 g/kg methionine had a higher hepatic expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol-7alpha-hydroxylase than rats fed less methionine. The phosphatidylcholine:phosphatidylethanolamine ratio in rat liver increased with rising dietary methionine concentration; the relative mRNA concentrations of phosphatidylethanolamine N-methyltransferase and cystathionine beta-synthase remained unaffected. Hepatocytes incubated in media supplemented with 100 or 200 micromol/l methionine had a higher cholesterol synthesis than hepatocytes incubated in a medium supplemented with 50 micromol/l methionine; the LDL uptake in hepatocytes was independent of the methionine concentration of the medium. In conclusion, the present study suggests that dietary methionine induces hypercholesterolaemia at least in part via an enhanced hepatic cholesterol synthesis.     

Low levels of viscous hydrocolloids lower plasma cholesterol in rats primarily by impairing cholesterol absorption

Hydrocolloids have been proposed as cholesterol-lowering agents, but their viscosity limits their use in human nutrition. A low level (1 %) of hydrocolloids (guar gum, (GG); xanthan gum, (XG); and konjac mannan) was investigated in rats fed 0.2 g/100 g cholesterol diets. Food intake and body weight gain were not altered by the diets. Bile flow and cholesterol bile flux were not modified by diet, whereas the bile acid flux was greater in rats fed hydrocolloid diets. The cecal pool of bile acids was greater than control rats only in rats fed the XG diet (+71%, P<0.001). The fecal excretion of neutral sterols was stimulated in rats fed the hydrocolloid diets; cholesterol apparent digestibility (60% in controls) was reduced to 30-36% in rats fed hydrocolloids. Bile acid fecal excretion was not altered by diet treatment. As a result, apparent steroid balance was about +40 micromol/d in controls and only +10 to +20 micromol/d in rats fed hydrocolloids. Both plasma cholesterol and triglycerides were significantly lower than controls in rats fed XG, but only cholesterol was lower in rats fed the GG diet. These effects were essentially found in the d <1.040 kg/L fraction. Liver cholesterol content was significantly lower than in controls in rats fed the GG or XG diets. Liver HMG CoA reductase was not affected by the hydrocolloid diets. In conclusion, a low percentage of viscous hydrocolloids lowers plasma cholesterol in cholesterol-fed rats. Inhibition of intestinal cholesterol absorption may be the primary mechanism.     

Amino acid supplementation decreases plasma and liver triacylglycerols in elderly

ObjectiveHypertriglyceridemia is a risk factor for coronary heart disease. The aim of this study was to determine the effect of amino acid (AA) supplementation on plasma, liver, and muscle lipid concentrations and insulin sensitivity in the elderly.MethodsTwelve impaired glucose tolerant elderly (mean ± SD 67.0 ± 5.6 y of age, seven women and five men) ingested 11 g of essential AAs plus arginine twice a day for 16 wk, after a 7-wk control run-in. Diet and activity were not otherwise modified. Plasma lipid concentrations and oral glucose tolerance were measured every fourth week and tissue lipid concentrations (magnetic resonance spectroscopy) every eighth week.ResultsNo changes in plasma lipids were observed during the control run-in. AA supplementation lowered plasma triacylglycerol (TG; P < 0.001), total cholesterol (P = 0.048), and very low-density lipoprotein cholesterol (P < 0.001) concentrations. Plasma TG decreased ～20% from the initial value of 1.45 ± 0.18 mmol/L (mean ± SE, 128 ± 16 mg/dL), with the greatest decrease in the subjects starting out with the highest concentrations (r = ?0.83). Similarly, liver fat content (liver TG/Intralipid standard) decreased ～50% from the initial value of 0.34 ± 0.06 (P = 0.021, n = 8), with the greatest decrease in the subjects who initially had the highest values (r = ?0.86). Intramuscular fat content and insulin sensitivity did not change.ConclusionDiet supplementation with AAs lowers plasma TG, total cholesterol, and very low-density lipoprotein cholesterol concentrations and liver lipid content in impaired glucose tolerant elderly. AA supplementation may have a potential role in the treatment of hypertriglyceridemia or hepatic steatosis.