Correlation of suppressed linoleic acid metabolism with the hypocholesterolemic action of eritadenine in rats

The dose-dependent effects of dietary eritadenine on the metabolism of linoleic acid and on the plasma cholesterol concentration were investigated to clarify the mechanism of the hypocholesterolemic action of eritadenine in rats. Rats were fed control or eritadenine-supplemented (2 to 20 mg/kg) diets for 14 d. Eritadenine supplementation significantly decreased both the plasma cholesterol concentration and the 20:4n-6/18:2n-6 ratio of liver microsomal and plasma phosphatidylcholine (PC) in a dose-dependent manner. Eritadenine was also found to decrease the activity of delta 6 desaturase in liver microsomes; there was significant correlation between the delta 6-desaturase activity and the 20:4n-6/18:2n-6 ratio in the PC of liver microsomes (r = 0.989, P < 0.001) or plasma (r = 0.986, P < 0.001). Certain plasma PC molecular species, as represented by 16:0-18.2, were increased by eritadenine in a dose-dependent manner, and certain plasma PC molecular species, as represented by 18:0-20:4, were conversely decreased by eritadenine. There was a significant correlation between the plasma total cholesterol concentration and the proportion of the sum of plasma PC molecular species which contain 18:1 or 18:2 in the sn-2 position. These results support the idea that the suppression of linoleic acid metabolism by eritadenine might be associated with the hypocholesterolemic action of eritadenine.     

Cloning and expression of a chicken alpha-amylase gene

The effects of cabbage leaf protein concentrate (CLPC) on serum and liver lipid concentrations were determined in rats fed cholesterol-enriched and cholesterol-free diets. In rats fed the cholesterol-enriched diet with CLPC, total cholesterol, triacylglycerol and phospholipid concentrations in both the serum and liver, as well as the atherogenic index diet were significantly lower than those of the rats fed a casein diet. A supplement of methionine to the CLPC diet raised serum HDL-cholesterol and body weight gain, indicating that the addition of methionine to the CLPC diet is not only available to improve the nutritive value of CLPC but also to lower the atherogenic index. In rats fed the cholesterol-free diet, the liver total cholesterol and triacylglycerol concentrations of the CLPC-fed rats also showed lower values than those of the casein-fed rats, however, the serum total cholesterol concentration of the CLPC-fed rats did not differ from that of the casein-fed rats.     

Dietary stearic acid reduces plasma and hepatic cholesterol concentrations without increasing bile acid excretion in cholesterol-fed hamsters

Although there is general agreement that saturated fatty acids elevate plasma cholesterol concentrations, the relative effects of individual fatty acids on cholesterol and bile acid metabolism are less clear. In this study, cholesterol and bile acid responses to diets enriched in different saturated fatty acids were investigated in hamsters. The six diets examined were as follows: 5% fat (g/100 g) enriched in palmitic acid (16:0) with no cholesterol, 5% fat 16:0-enriched, 0.05% cholesterol (wt/wt), and four diets containing 0.05% cholesterol and 15% fat with each diet enriched in lauric (12:0), myristic (14:0), palmitic (16:0), or stearic acid (18:0). Total plasma cholesterol concentration was significantly greater in hamsters fed the 14:0-enriched diet relative to those fed the 18:0-enriched diet (P < 0.05). Both plasma and liver cholesterol concentrations of hamsters fed 18:0 did not differ from those of the group fed no dietary cholesterol. In all instances, differences in total plasma cholesterol were accounted for within the HDL fraction; no significant treatment differences in VLDL or LDL cholesterol were found. Total daily fecal bile acid excretion was higher in hamsters fed the 15% fat 16:0 diet compared with those fed no dietary cholesterol (P < 0.05), but not significantly different from other treatment groups. There was greater deoxycholic acid excretion (P < 0.05) from hamsters fed the 14:0 and 16:0 diets compared with those fed the 18:0-enriched diet. Small intestinal + gallbladder bile acids, an index of pool size, did not differ significantly among the groups. The observed relative hypocholesterolemic effect of stearic acid was not mediated by increased bile acid excretion.     

Lysine: arginine ratio of a protein influences cholesterol metabolism. Part 1--Studies on sesame protein having low lysine: arginine ratio

The effect of globulin fraction with a lysine: arginine (lys:arg) ratio 0.67, isolated from sesame (Sesamum Indicum) seeds on cholesterol metabolism was studied in rats fed cholesterol free and cholesterol containing diet and compared with casein (lys:arg ratio-2.0). Rats fed sesame seed globulin showed significantly lower concentrations of cholesterol in the serum and aorta. The decrease in serum was manifested in both HDL and LDL + VLDL fractions. There was increased cholesterogenesis in the liver as was evident from increased incorporation of labeled acetate into cholesterol and increased activity of 3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase. Increased hepatic diversion of cholesterol to bile acid synthesis and increased fecal excretion of bile acids and sterols were also observed in rats fed sesame seed globulins. Rats fed sesame globulins also showed significantly higher activity of lipoprotein lipase in the heart and adipose tissue and that of plasma Lecithin: cholesterol acyltransferase (LCAT). These studies suggest that low lysine: arginine ratios of a protein exert hypocholesterolemic effects.     

Soybean protein suppresses hepatic lipogenic enzyme gene expression in Wistar fatty rats

The effects of dietary soybean protein on lipogenic enzyme gene expression in livers of genetically fatty rats (Wistar fatty) have been investigated. When Wistar fatty rats and their lean littermates (7-8-wk old) were fed a casein or soybean protein isolate diet containing hydrogenated fat (4% hydrogenated fat plus 1% corn oil) or corn oil (5%) for 3 wk, the hepatic messenger RNA concentrations and activities of lipogenic enzymes were significantly lower in rats fed soybean protein than in those fed casein, regardless of genotype or dietary fat. The conversion rates of thyroxine to triiodothyronine by liver microsomes and plasma triiodothyronine concentrations were lower in the fatty rats than in the lean rats and were significantly greater in rats fed soybean protein than in those fed casein. Conversely, plasma and liver triacylglycerol concentrations were lower in soybean protein-fed fatty and lean rats than in those fed casein. The body weight was less in the fatty rats fed soybean protein than in those fed casein after 3 wk of feeding. Moreover, dietary polyunsaturated fatty acids suppressed lipogenic enzyme gene expression in the lean rats but did not in the fatty rats. Dietary soybean protein appeared to be useful for the reduction of obesity.     

Lipoprotein responses to fish, coconut and soybean oil diets with and without cholesterol in the Syrian hamster

Thirty-six young male Syrian hamsters were fed with test diets containing coconut oil, soybean oil or fish oil with and without 0.5% cholesterol for 6 weeks. Without dietary cholesterol supplementation, animals on the fish oil diet had significantly lower plasma total triglyceride (TG) and total cholesterol than those on the coconut oil or soybean oil diet. The decrease of TG was seen mainly in the very low density lipoprotein (VLDL) fraction. The degree of decrease in cholesterol was similar in all of the lipoprotein fractions. With 0.5% dietary cholesterol supplementation, there was no significant difference in plasma TG level among the three dietary groups. However, the fish oil group had significantly higher plasma cholesterol than the coconut oil and soybean oil groups. The increase of cholesterol was mainly in the VLDL and low density lipoprotein (LDL) fractions. In contrast to the plasma cholesterol level, the hepatic cholesteryl ester content was significantly lower in the cholesterol-supplemented fish oil group than in the coconut oil and soybean oil counterparts. The cholesterol-supplemented fish oil group showed higher liver microsomal acyl-coenzyme A:cholesterol acyltransferase activity than the other two groups, while there was no significant difference in the excretion of fecal neutral and acidic sterols among the three dietary groups.     

Effects of spinach leaf protein concentrate on the serum cholesterol and amino acid concentrations in rats fed a cholesterol-free diet

The effects of spinach leaf protein concentrate (SPPC) on serum and liver lipid concentrations and on serum free amino acid concentrations were examined in rats fed a cholesterol-free diet containing 2 and 10% fats. The serum total cholesterol, triacylglycerol and phospholipid concentrations in the rats fed an SPPC diet containing 2% corn oil were significantly lower than those of the rats fed a corresponding casein diet. When 10% corn oil or lard was used, the serum cholesterol-lowering effect of the SPPC became insignificant, but the serum and liver triacylglycerol concentrations were kept at significantly lower levels. Both the amounts of fecal neutral steroids and bile acids were significantly higher in the rats fed the SPPC than those of the casein-fed rats. The concentrations of serum threonine, serine, glutamine, glycine, cystine, and isoleucine were significantly higher in the rats fed the SPPC diet containing 2% corn oil compared with those of the control rats, but when the dietary fat was raised to 10%, only glycine showed a higher serum concentration. These results indicate that the SPPC has a stronger cholesterol-lowering effect at a lower dietary fat level, 2%, and the activity is partly due to the inhibition of intestinal absorption of cholesterol and bile acid, and partly due to an increase in the concentration of some of the serum amino acids.     

A comparison of hypocholesterolemic activity of beta-sitosterol and beta-sitostanol in rats

The hypocholesterolemic activity of beta-sitosterol and its hydrogenated product, beta-sitostanol (dihydrositosterol or stigmastanol) has been compared in young male rats. When cholesterol was included in the diet, sitostanol consistently exhibited significantly greater hypocholesterolemic activity than sitosterol. There were no apparent differences in the effects of the sterol and the stanol on the concentration of liver cholesterol and triglyceride. Increases in plasma triglyceride due to feeding sitosterol were not observed with sitostanol. Incorporation of dietary sitostanol into plasma, liver and other tissues was always negligible, and thus this stanol was almost completely recovered in feces, while there was considerable deposition of sitosterol (mean fecal recovery being 85% to 92%). The increase in fecal output of dietary cholesterol was significantly greater with the stanol than with sterol. There was no demonstrable negative effect on growth and weight of major visceral tissues in rats fed the sterol as well as the stanol. These observations together with those reported previously indicate that hydorgenation of phytosterols is a novel approach to enhance their hypocholesterolemic activities without influencing the relative safety of the initial sterols.     

Effect of S-adenosyl-L-methionine and dilinoleoylphosphatidylcholine on liver lipid composition and ethanol hepatotoxicity in isolated perfused rat liver

We investigated whether S-adenosyl-L-methionine (SAMe), dilinoleoylphosphatidylcholine (DLPC), or SAMe + DLPC influence liver lipid composition as well as acute ethanol hepatotoxicity in the isolated perfused rat liver (IPRL). SAMe (25 mg/kg intramuscularly three times a day) was administered for five consecutive days, while DLPC was administered intraperitoneally for five days. The liver was then isolated, perfused with taurocholate to stabilize bile secretion, and exposed to 0.5% ethanol for 70 min. SAMe, without changing total phospholipid (PL) content, induced an increase in the phosphatidylcholine/phosphatidylethanolamine (PC/PE) molar ratio in both liver homogenate and microsomes and a significant enrichment of 16:0-20:4 and 18:0-20:4 PC molecular species. DLPC induced a significant enrichment of PL in liver homogenate and microsomes due to a contemporary increase in PC and PE. The PC enrichment specifically involved 16:0-20:4 and 18:0-20:4 PC molecular species besides the HPLC peak containing the administered 18:2-18:2 PC species. DLPC + SAMe increased the concentration of PC in liver homogenate and microsomes due to a specific enrichment of 16:0-22:6, 16:0-20:4, and 18:0-20:4 PC molecular species, and the HPLC peak containing the administered 18:2-18:2 PC species. Ethanol acute exposure in the control IPRLs for 70 min induced a depletion of cholesterol in both liver homogenate and microsomes without significant changes in the composition of PL classes and PC molecular species. SAMe, DLPC, or SAMe + DLPC counteracted the cholesterol depletion induced by ethanol, indicating that phospholipid changes promoted by these treatments all induce a major resistance of liver membranes to the effect of ethanol. Ethanol administration in control IPRLs induced a fivefold increase of AST and LDH release in the perfusate, depletion of glutathione in homogenates and mitochondria, decreased oxygen liver consumption, and inhibition of bile flow. These effects of ethanol were significantly antagonized by SAMe. In contrast, DLPC alone only minimally attenuated enzyme release in the perfusate and the inhibitory effect of ethanol on bile flow, but it failed to influence the depletion of total and mitochondrial glutathione or the depressed oxygen consumption induced by ethanol. DLPC, administered together with SAMe, added nothing to the protective effect of SAMe against ethanol hepatotoxicity and cholestasis. In conclusion, this study demonstrates that both SAMe and DLPC induced marked modifications in the lipid composition of liver membranes with a similar enrichment of polyunsaturated PC molecular species. Only SAMe, however, significantly protected against the hepatotoxic and cholestatic effect of acute ethanol administration, an effect associated with maintained normal glutathione mitochondrial levels and oxygen liver consumption. This indicates that the protective effect of SAMe against ethanol toxicity is linked to multiple mechanisms, the maintenance of glutathione levels probably being one of the most important.     

Dietary soybean protein compared with casein retards senescence in the senescence accelerated mouse

The effects of replacing dietary casein with soybean protein on mean life span, mean life span of the last one-tenth of a group, grading scores of senescence and deposition of senile amyloid were investigated in senescence accelerated mice (SAM-P/1) compared with a control strain (SAM-R/1). SAM-R/1 mice fed the soybean protein-containing diet had mean life spans of 618 +/- 42 d (males) and 578 +/- 62 d (females), 58% (males) and 44% (females) longer than those of corresponding casein fed mice (P < 0.01). Similarly, in SAM-P/1 mean life-spans were 265 +/- 16 d (males) and 307 +/- 23 d (females) in the soybean diet group, 27% (males) and 30% (females) longer than in the casein diet groups (P < 0.01). The mean life span of the last one-tenth of each group fed soybean protein was significantly longer than the corresponding group fed casein. In SAM-R/1 mice, pathological studies revealed that severe secondary amyloid deposition (amyloid A protein) in the kidneys, spleen, stomach and liver was significantly suppressed, in males only, by replacing casein with soybean protein (P < 0.01). The occurrence of contracted kidneys caused by the infiltration of amyloid A protein was suppressed in SAM-R/1 mice fed the soybean protein-containing diet (P < 0.05). The deposition of senile amyloid in SAM-P/1 mice with aging was retarded by replacing casein with soybean protein (P < 0.01). These results indicate that dietary protein source is important in modulating the advance of senescence in SAM mice.     

Effects of diets containing tallow and soybean oil with and without cholesterol on hepatic metabolism of lipids and lipoproteins in the preruminant calf

The effects of long-chain fatty acids (230 g/kg of dietary DM) from tallow and from soybean oil, with or without cholesterol (10 g/kg of dietary DM), on hepatic lipid contents and on in vivo hepatic production rates of lipids and lipoproteins were investigated in 22 preruminant male calves fitted with chronic catheters and with electromagnetic blood flow probes implanted in the hepatic vessels. Diets containing soybean oil and soybean oil with cholesterol led to the development of triglyceride infiltration in the liver and to higher apparent hepatic secretion of very low density lipoproteins than did diets containing tallow or tallow with cholesterol. Addition of cholesterol to diets favored accumulation of low density lipoproteins in plasma and the net apparent secretion of these particles by the liver, especially for the diet containing soybean oil with cholesterol. Regardless of the diet, calf liver clearly removed large high density lipoproteins of type 1 that were rich in cholesteryl esters but secreted heavy high density lipoproteins that were rich in proteins. The intensity of removal of high density lipoproteins of type 1 by the liver depended on the plasma concentration of these particles, probably by mass action. This removal did not prevent the accumulation of high density lipoproteins of type 1 in plasma, such as it did in calves fed soybean oil.     

A rice protein isolate alters 7,12-dimethylbenz[alpha]anthracene-induced mammary tumor development in female rats

The effects of a rice protein isolate (RPI) on 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced mammary tumor progression were investigated in female Sprague-Dawley rats. At 6 weeks of age, rats were fed a casein, RPI or soybean protein isolate (SPI) diet, respectively. After 1 week, DMBA was administered orally at the dose of 30 mg/kg body weight. The mean tumor number per tumor-bearing rat at autopsy was significantly lower only in rats fed RPI than in those fed casein. Palpable tumors at the mid point of the experiment were significantly lower in rats fed RPI and SPI than in those fed casein. Serum estradiol-17 beta concentrations were lower in rats fed the SPI (but not in those fed RPI) than in those fed casein. In a further experiment, no differences were found in hepatic microsomal DMBA-arylhydrocarbon hydroxylase activity after 7 days of feeding the respective diets. These results suggest that RPI exerts its inhibitory effect on DMBA-induced mammary tumorigenesis irrespective of changes in circulating estrogens or modulation of hepatic DMBA metabolism.     

Soy protein has no hypocholesterolemic action in mice because it does not stimulate fecal steroid excretion in that species

We compared the effects of dietary soy protein isolate (SPI) and casein on plasma cholesterol level and fecal steroid excretion in rats, mice and hamsters. In rats, compared with casein, SPI significantly stimulated fecal steroid excretion in 9 out of 12 experiments with or without dietary cholesterol, whereas it suppressed plasma cholesterol level in 5 experiments and tended to suppress that, though not significantly, in 4 experiments. In mice, on the contrary, no significant difference was observed between the effects of casein and SPI on either the fecal steroid excretion or plasma cholesterol level in most of 12 experiments in which three different strains were tested. High-molecular-weight fraction of undigested residue of SPI exhibited marked hypocholesterolemic and steroid excretion-stimulating effects in rats and hamsters, whereas it showed only mild effects in mice. The species-dependent difference indicated the existence of inverse correlation between fecal steroid excretion and plasma cholesterol level and supported the view that in species like rat and hamster, but not mice, SPI lowers plasma cholesterol level by stimulating fecal steroid excretion.     

Tetradecylthioacetic acid incorporated into very low density lipoprotein: changes in the fatty acid composition and reduced plasma lipids in cholesterol-fed hamsters

The mechanism behind the hypolipidemic effect of tetradecylthioacetic acid (CMTTD, a non-beta-oxidizable 3-thia fatty acid) was studied in hamsters fed a high cholesterol diet (2%), which resulted in hyperlipidemia. Treating hyperlipidemic hamsters with CMTTD resulted in a progressive hypocholesterolemic and hypotriacylglycerolemic effect. Decreased plasma cholesterol was followed by a 39% and 30% reduction in VLDL-cholesterol and LDL-cholesterol, respectively. In contrast, the HDL-cholesterol content was not affected, thus decreasing the VLDL-cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios. 3-Hydroxy-3-methylglutaryl- (HMG) CoA reductase activity and its mRNA level were unchanged after CMTTD administration. Also, the LDL receptor and LDL receptor-related protein (LRP-4) mRNAs were unchanged. The decrease in plasma triacylglycerol was accompanied by a 45% and 56% reduction in VLDL-triacylglycerol and LDL-triacylglycerol, respectively. The hypolipidemic effect of CMTTD was followed by a 1.4-fold increase in mitochondrial fatty acid oxidation and a 2.3-fold increase in peroxisomal fatty acid oxidation. CMTTD treatment led to an accumulation of dihomo-gamma-linolenic acid (20:3n-6) in liver, plasma, very low density lipoprotein, and heart. Noteworthy, CMTTD accumulated more in the heart, plasma, and VLDL particles compared to the liver, and in the VLDL particle alpha-linolenic acid (18:3n-3) decreased whereas eicosatetraenoic acid (20:4n-3) increased. In addition, linoleic acid (18:2n-6) and the total amount of polyunsaturated fatty acids decreased, the latter mainly due to a decrease in n-6 fatty acids. The present data show that CMTTD was detected in plasma and incorporated into VLDL, liver, and heart. The relative incorporation (mol%) of CMTTD was heart > VLDL > liver. In conclusion, CMTTD causes both a hypocholesterolemic and hypotriacylglycerolemic effect in hyperlipidemic hamsters.     

Comparison of the kinetics of pancreatic secretion and gut regulatory peptides in the plasma of preruminant calves fed milk or soybean protein

Exocrine secretion from the pancreas and concentrations of cholecystokinin, gastrin, secretin, and somatostatin in plasma were measured in relation to feeding in 70- to 120-d-old preruminant calves fed either a milk diet or a soybean diet. Pancreatic fluid was continuously collected, measured, and reintroduced in catheterized calves. Blood samples were withdrawn for measurements of gut regulatory peptide concentrations in plasma. A slight increase in outflow of pancreatic fluid was observed 30 min before the milk diet was introduced but not before the soybean diet was fed. In contrast, concentrations and outflows of protein and trypsin immediately after feeding were higher when calves were fed the soybean diet. Overall, during the first 5 h postfeeding, the outflow of pancreatic fluid was 40% higher when the milk diet was fed than when the soybean diet was fed. No difference in outflow of protein was observed, but that of trypsin was 82% higher when the soybean diet was fed. This enhanced enzyme secretion could have been related to the increased plasma concentrations of gastrin and cholecystokinin after the soybean diet was fed. Secretin release was less in calves fed the milk diet that in calves fed the soybean diet during the first 2 h postfeeding, suggesting that this gut peptide along with gastrin and cholecystokinin, contributed to the stimulation of enzyme secretion. Plasma gut regulatory peptides could be influenced by the soybean diet, which does not coagulate in the stomach, inducing faster gastric emptying of protein and fat, and by the chemical form of protein from the soybean diet and the lower susceptibility of these proteins to protease compared with casein. However, the resulting enhancement of pancreatic trypsin secretion and activity seemed to be insufficient to increase the digestibility of soybean protein up to a level similar to that of milk.     

Growth is compromised in rats fed ozone-treated casein

Modified casein containing few phenylalanine residues and no other aromatic amino acid residues was obtained by ozonolysis of casein. Although 68% of phenylalanine was decomposed by ozonolysis of casein, ozonolysis caused alterations beyond the destruction of aromatic amino acid residues. Nearly the same degree of decomposition of amino acid residues was observed in casein ozonated after predigestion by pepsin. Rats were fed diets containing 8% casein supplemented with methionine and aspartic acid (8C-AA), 8% ozonated casein supplemented with methionine and free amino acids lost by ozonolysis (8OC-AA), 8% casein ozonated after predigestion by pepsin supplemented with methionine and free amino acids lost during preparation (8POC-AA) or 7.6% amino acid mixture. The growth of rats fed the 8OC-AA diet was significantly lower than that of those fed 8C-AA or 7.6AA diets. The growth of rats fed the 8POC-AA diet was comparable to growth of those fed 8OC-AA. The biological values of the 8OC-AA and 8POC-AA were comparable to that of 8C-AA, but true digestibility of 8OC-AA was significantly lower than that of 8C-AA. True digestibility 8POC-AA was significantly improved relative to 8OC-AA, but the growth of rats fed 8POC-AA was not improved relative to that of those fed 8OC-AA. Kidney and cecum weights of rats fed 8OC-AA and 8POC-AA were significantly heavier than those of the 8C-AA-fed group, although histopathological examination of kidneys showed no deterioration compared to that of the 8C-AA-fed group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Different degrees of moderate iron deficiency modulate lipid metabolism of rats

Severe iron deficiency affects lipid metabolism. To investigate whether moderate iron depletion also alters lipid variables-including lipid levels in serum and liver, hepatic lipogenesis, and fatty acid composition indicative of an impaired desaturation-we carried out experiments with rats fed 9, 13, and 18 mg iron/kg diet over a total of 5 wk. The study also included three pair-fed control groups and an ad libitum control group, fed with 50 mg iron/kg diet. The iron-depleted rats were classified as iron-deficient on the basis of reduced serum iron, hemoglobin concentration, and hematocrit. All moderately iron-deficient rats had significantly lower cholesterol concentrations in liver and serum lipoproteins than their pair-fed controls. Rats with the lowest dietary iron supply had higher concentrations of hepatic phosphatidylcholine (PC) and phosphatidylethanolamine (PE), lower activities of glucose-6-phosphate dehydrogenase, malic enzyme and fatty acid synthase, and higher triacylglycerol concentrations in serum lipoproteins than the corresponding pair-fed control rats. Moderate iron deficiency also depressed the serum phospholipid level. Moreover, several consistent significant differences in fatty acid composition of hepatic PC and PE occurred within moderate iron deficiency, which indicate impaired desaturation by delta-9 and delta-6 desaturases of saturated and essential fatty acids. We conclude that lipid variables, including cholesterol in liver and serum lipoproteins as well as fatty acid desaturation, reflect the gradations of iron status best and can be used as an indicator of the degree of moderate iron deficiency.     

Hepatic and adrenal changes in rabbits associated with hyperlipidemia caused by a semi-synthetic diet

Several investigators have reported that feeding a semi-synthetic diet of casein and dextrose to New Zealand White (NZW) rabbits will increase total serum cholesterol concentration, principally through an increase in the beta-lipoprotein fractions, thereby creating a useful model for atherosclerosis research. Although there is evidence to suggest that the dextrose/casein diet alters low-density lipoprotein receptor and bile acid clearance of cholesterol, the underlying mechanism is not completely understood. The effects of the diet on the overall physiology of the rabbit have received little attention. In this study feeding a diet of casein and dextrose of male NZW rabbits for 4 weeks resulted in changes in the serum lipid concentrations. During that time the rabbits fed the dextrose/casein diet gained less weight than did control rabbits. In the test diet rabbits, liver aspartate and alanine transaminase activities were increased from baseline values of 27 +/- 2 U/L and 89 +/- 9 U/L respectively to 112 +/- 21 U/L and 281 +/- 34 U/L respectively, then returned to the high end of the reference range. Necropsy findings included hepatomegaly caused by vacuolar hepatopathy in 19 or 20 experimental rabbits; rabbits fed the control diet had no hepatic lesions. Ultrastructural analysis revealed that enlargement of the liver cells was due to glycogen deposition. Adrenal glands from animals fed the experimental diet had a minimal change in the size of the adrenocortical cells consisting of slight ballooning and rarefaction of the cytoplasm. In a second study the level of dietary fiber was doubled. This resulted in a three-fold increase in lipid concentrations, compared with the fivefold increase in the first study. The liver enzyme activities were increased to the same extent as in the first study. Histologic changes were comparable to those in the first study. The activity of hepatic cholesterol 7alpha-hydroxylase was 3.7 +/- 0.4 pmol/min/mg of protein, compared with the control value of 7.7 +/- 1.1 pmol/min/mg of protein (P < 0.05) in the second study. The improved rate of weight gain and the lesser increase in total serum cholesterol concentration in the second study with increased dietary fiber suggest that two separate activities may be involved. Although the level of dietary fiber may be related to weight gain and total serum cholesterol values, the relation to the decrease in liver transaminase activities in study 1 was probably coincidental. It appears that the dextrose/casein diet causes decreased activity of hepatic cholesterol 7alpha-hydroxylase, which could cause a decrease in the biliary excretion of cholesterol.     

Diet modification alters plasma HDL cholesterol concentrations but not the transport of HDL cholesteryl esters to the liver in the hamster

These studies were undertaken to investigate the mechanism whereby diet modification alters the plasma concentration of high density lipoprotein (HDL) cholesteryl ester and apoA-I and to determine whether diet-induced alterations in circulating HDL levels are associated with changes in the rate of reverse cholesterol transport. Rates of HDL cholesteryl ester and apoA-I transport were measured in hamsters fed a control low-cholesterol, low-fat diet or the same diet supplemented with soluble fiber (psyllium) or with cholesterol and triglyceride (Western-type diet). The Western-type diet increased the plasma concentration of HDL cholesteryl ester by 46% compared to the control diet and by 86% compared to the psyllium-supplemented diet; nevertheless, the absolute rates of HDL cholesteryl ester transport to the liver were identical in the three groups. Diet-induced alterations in circulating HDL cholesteryl ester levels were due to changes in the rate of HDL cholesteryl ester entry into HDL (whole body HDL cholesteryl ester transport) and not to regulation of HDL cholesteryl ester clearance mechanisms. The Western-type diet increased the plasma concentration of HDL apoA-I by 25% compared to the control diet and by 45% relative to the psyllium-supplemented diet. Diet-induced alterations in plasma HDL apoA-I concentrations were also due entirely to changes in the rate of apoA-I entry into HDL (whole body HDL apoA-I transport). These studies demonstrate that the absolute flux of HDL cholesteryl ester to the liver, which reflects the rate of reverse cholesterol transport, remains constant under conditions in which plasma HDL cholesteryl ester concentrations are altered over a nearly 2-fold range by diet modification.     

Resistant proteins alter cecal short-chain fatty acid profiles in rats fed high amylose cornstarch

The objective of this study was to examine the physiologic importance of undigested protein on cecal fermentation in rats fed a low (LAS) and high (HAS) amylose cornstarch. In Experiment 1, rats were fed diets containing LAS (655 g/kg diet) with one of four protein sources: casein, rice (RP), potato (PP) or soybean protein (SP) at 250 g/kg diet for 15 d. Apparent digestibilities of casein, RP, SP and PP were 96, 94, 93 and 92%, respectively. In rats fed the LAS diet with casein, acetate, propionate and succinate were the major cecal organic acids. The succinate pools in rats fed RP or SP were significantly lower than in those fed casein, whereas butyrate did not differ. Butyrate was significantly higher in rats fed PP, but succinate was the same as in rats fed casein. In Experiment 2, rats were fed diets containing HAS (200 g/kg diet) with one of the four protein sources at 250 g/kg diet for 10 d. HAS was substituted for the same amount of LAS. In rats fed the HAS diet, succinate was the major acid in rats fed casein; in rats fed RP or PP, however, the pools of this acid were significantly lower than in those fed casein, whereas butyrate was significantly higher in rats fed RP or PP. Fecal starch excretion was significantly lower in rats fed RP or PP than in those fed casein. In Experiment 3, rats were fed the casein-HAS diet with graded levels of PP (0, 10, 30, 50, 100 and 250 g/kg diet) for 14 d. The PP was substituted for the same amount of casein. Cecal butyrate was low in rats fed up to 100 g of PP/kg diet and then rose with 250 g of PP/kg diet. In Experiment 4, ileorectostomized rats were used and fed the same diets described in Experiment 3 for 9 d. The ileal starch/nitrogen ratio declined with increasing dietary PP, due solely to greater nitrogen excretion, whereas starch excretion was unaffected. In Experiment 5, rats were fed the casein-HAS diet with or without 60 g of artificial resistant protein/kg diet for 10 d. The resistant protein (apparent digestibility, 63%) was substituted for the same amount of casein. Rats fed the casein-HAS diet with resistant protein had significantly greater cecal butyrate and lower succinate than those fed the casein-HAS diet. These data show that large bowel fermentation of starch is altered by dietary protein. They support the hypothesis that nondigested protein, namely, resistant protein, may control fermentation efficiency as well as the fermentation profile of HAS, possibly as a result of a change in microflora through the change in the ratio of starch to nitrogen in the cecum.