Influence of maternal cholestyramine treatment on cholesterol and bile acid metabolism in adult offspring

To reduce ileal reabsorption of bile acids and to deplete hepatic cholesterol pools, female rats were fed a diet containing 5% (wt/wt) cholestyramine from 4 days prior to mating. Control rats were fed the same diet without cholestyramine. In one group on day 20 of gestation diet-fed dams and their fetuses were investigated. Additional pups were raised in litters of eight and nursed by their mothers for 30 days at which time they were weaned to the control diet. All dams were given the control diet from day 14 of lactation; at no time did neonates have access to cholestyramine. Offspring were raised until 3 months of age then fed the control, cholestyramine or a high fat, high cholesterol diet for 5 days. Maternal cholestyramine produced significant elevation of fetal hepatic 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase; fetal 7 alpha-hydroxylase (7 alpha-OH) activity, plasma cholesterol and triglyceride levels, however, were not significantly altered. The elevated HMG-CoA reductase activity persisted in liver and in addition was present in jejunum of 3-month-old male offspring challenged with the control or cholestyramine diet for 5 days. When challenged with the high fat, high cholesterol diet, male offspring from cholestyramine-treated dams had significantly higher plasma cholesterol levels but HMG-CoA reductase and 7 alpha-OH activity similar to controls. Maternal treatment had no apparent effect on plasma triglyceride or hepatic 7 alpha-OH in 3-month-old male offspring.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatic cholesterol and fatty acid synthesis in pregnant and fetal rats: effect of maternal dietary fat and cholestyramine.

Previous studies from this laboratory have demonstrated that 20% rather than 5% (wt/wt) safflower oil or addition of 5% (wt/wt) cholestyramine to the diet of pregnant rats leads to an increase in the activity of 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme of cholesterol synthesis, in the fetal liver. Total cholesterol, however, was not altered in fetal plasma or liver. The effect of these diets on cholesterol and fatty acid synthesis in vivo was therefore studied in fetal and maternal liver. In fetuses of rats fed a reference nonpurified diet, rates of hepatic cholesterol and fatty acid synthesis decreased from gestation d 20 to 21. In contrast, total and active 3-hydroxy-3-methyl-glutaryl CoA reductase activity increased. Adding cholestyramine to the diet or modifying the quantity of safflower oil fed had no effect on fetal hepatic lipogenesis. Maternal hepatic cholesterol synthesis was greater in rats fed cholestyramine, whereas fatty acid synthesis was lower in the dams fed the diet containing 20% compared with 5% safflower oil. The results suggest near-term fetal liver 3-hydroxy-3-methylglutaryl CoA reductase activities do not reflect fetal cholesterol synthesis in vivo.     

Changes in plasma cholesterol density distribution of young adult male rats fed a high fat and cholesterol diet following maternal cholestyramine treatment

The effects of feeding cholestyramine to pregnant rats, which has been shown to increase the fetal hepatic rate-limiting enzyme in cholesterol synthesis, HMG CoA reductase, on the plasma cholesterol density distribution was studied in the young adult male rat offspring before and after feeding a diet high in fat and cholesterol. As in previous studies, offspring of rats fed cholestyramine during pregnancy had a plasma total cholesterol level similar to controls when fed a low fat and cholesterol diet, but higher than controls when fed a 20% (wt/wt) fat plus 5% (wt/wt) cholesterol diet. Analyses of the plasma cholesterol density distribution by continuous gradient ultracentrifugation showed that, compared to control rats, rats born to dams fed cholestyramine had more cholesterol in the higher density regions of plasma before and after a 7-d high fat and cholesterol diet challenge. After a 4- or 7-d diet challenge, rats fed cholestyramine had 2-3 times more cholesterol in the d less than or equal to 1.006 g/ml range of plasma compared to the control offspring. The results suggest that long term changes in cholesterol metabolism due to early nutrition in the rat may include altered plasma or intestinal lipoprotein metabolism, rather than an effect specific to hepatic cholesterol synthesis.     

Effect of dietary fat content and composition during pregnancy on fetal hepatic HMG CoA reductase activities and lipids in rats

The effects of diets containing 20% (wt/wt) safflower, olive or palm oil or 5% (wt/wt) safflower oil when fed throughout gestation on hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity and on plasma and liver lipids were studied in fetal rats at d 21 of gestation. Hepatic total and active HMG CoA reductase activity, plasma free cholesterol and liver triglyceride and phospholipid 18:2(n-6) levels were higher in fetuses of rats fed 20% than in those of rats fed 5% safflower oil. Fetuses of rats fed olive oil had higher active HMG CoA reductase levels than fetuses of rats fed 20% safflower or palm oil; their total reductase activity was similar to that of the safflower oil group and higher than that for the palm oil group. Fetal liver and plasma cholesterol and triglyceride, as well as liver phospholipid concentrations, were not altered by the type of oil fed. The diets containing safflower oil resulted in higher 18:2(n-6) and lower 18:1 levels in fetal liver phospholipid and triglycerides than did the diets containing palm or olive oil. These studies demonstrate that fetal liver HMG CoA reductase activity is influenced by the maternal diet fat content and composition although the effect of specific fatty acids is unknown.     

Low arachidonic acid rather than alpha-tocopherol is responsible for the delayed postnatal development in offspring of rats fed fish oil instead of olive oil during pregnancy and lactation

This study was designed to compare in rats the effects of dietary fish oil and olive oil during pregnancy and lactation on offspring development, fatty acid profile and vitamin E concentration. From d 0 of pregnancy, female Sprague-Dawley rats were divided into two groups that were fed purified diets that differed only in their nonvitamin lipid components. One diet contained 10 g fish oil/100 g diet (FOD), whereas the other contained 10 g olive oil/100 g diet (OOD). At d 20 of gestation, maternal adipose tissue fatty acid profile did not differ between rats fed the two diets, whereas both maternal and fetal plasma and liver arachidonic acid (AA) contents were proportionally lower and eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid contents were higher in the FOD group than in the OOD group. alpha-Tocopherol concentration was lower in maternal and fetal plasma, liver and brain in the FOD group than in the OOD group. The postnatal increase in body weight and length was less and body and psychomotor maturation indices were delayed in pups from FOD-fed dams compared with those from OOD-fed dams. This difference was maintained when pups were cross-fostered at birth, with the delay in postnatal development present in the pups suckling dams fed FOD during lactation. At age 21 d, pups suckling dams fed FOD had lower AA and higher EPA and DHA concentrations in brain phospholipids. Although alpha-tocopherol in plasma and liver was lower in pups suckling dams fed FOD rather than OOD, brain alpha-tocopherol concentrations did not differ. Milk yield and milk alpha-tocopherol and AA concentrations were lower and EPA and DHA were higher in the milk of dams fed FOD compared with those fed OOD. Postnatal development indices and the proportion of plasma, liver and brain AA concentrations, although not plasma, liver and brain alpha-tocopherol concentrations, recovered to the values found in dams fed OOD when the FOD was supplemented with gamma-linolenic acid. However, postnatal development indices were not recovered when the FOD was supplemented with sufficient exogenous vitamin E to increase plasma and liver alpha-tocopherol concentrations above those in dams fed OOD. Thus, although feeding FOD during pregnancy and lactation decreases both alpha-tocopherol and AA concentrations, the latter deficiency rather than the former seems to be responsible for delayed postnatal development of rat pups.     

Effects of diets rich in fermentable carbohydrates on plasma lipoprotein levels and on lipoprotein catabolism in rats

This study was conducted to examine the effects of a combination of several dietary fibers (5% guar gum, 5% apple pectin, 15% wheat bran, 22% soybean fiber) and crude potato starch (23%) on plasma lipids and lipoproteins and on liver lipid concentration in rats fed a diet containing either 15% lard or 5% oil with or without dietary cholesterol/cholic acid. Male Wistar rats ate the test diets for 3 wk. The incorporation of fiber and crude potato starch into the diet resulted in a significant enlargement of the cecum; it also increased the concentration of volatile fatty acids and the pool of acetate, propionate and butyrate. Feeding this fermentable carbohydrate decreased plasma cholesterol and triglyceride levels in rats given a low fat diet and prevented the expected rise in plasma cholesterol and triglycerides in rats fed cholesterol/cholic acid or lard. Further studies of high density lipoprotein (HDL) composition, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoA reductase) activity and 125I-labeled human low density lipoprotein (LDL) turnover were done in the group fed the low fat diet without added cholesterol/cholic acid. The study of the HDL fraction in rats fed a diet rich in fermentable carbohydrates demonstrated a decrease in the HDL1 subpopulation and in the proportion of apolipoprotein E. Plasma clearance of intravenously injected 125I-labeled LDL was faster in rats fed this diet than in rats fed the fiber-free diet. In the liver, cholesterol and triglyceride levels were depressed whereas the activity of HMG-CoA reductase was increased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Maternal dietary fat type influences the growth and fatty acid composition of newborn and weanling rats

To determine whether the long-term consumption of different amounts or types of fat by female rats affects the growth and development of their progeny, Wistar rats were fed from weaning either a low fat diet (4.5% by weight) or one of three high fat (32%) diets containing predominantly beef tallow (high saturated fat), corn oil (high polyunsaturated fat) or equal portions of tallow and corn oil (high mixed fat). Offspring were killed at birth or weaning. Weight of newborn pups was lower with maternal consumption of high polyunsaturated fat diets. Carcass composition of newborn pups and body weight of weanling rats was unaffected by maternal diet. The percentage of carcass lipid was greater in weanling rats from all high fat-fed dams. In both newborn pups and weanling rats, percent composition in carcass lipids of 16:0, 16:1 and 18:1 fatty acids generally decreased and 18:2 increased as the high fat maternal diet became more unsaturated. The consumption of diets high in polyunsaturated fatty acids prior to and throughout gestation thus seemed to have a transitory effect on reducing fetal growth in rats.     

Regulation of cholesterol and lipoprotein metabolism in guinea pigs mediated by dietary fat quality and quantity.

The effects of dietary fat quality and quantity on regulation of cholesterol and lipoprotein metabolism were measured in guinea pigs. The animals were fed 7.5 or 15% (wt/wt) fat diets containing either polyunsaturated corn oil (CO), monounsaturated olive oil (OL) or saturated lard as the fat source. Dietary fat quality had a number of significant effects: animals fed the CO-based diet had lower plasma LDL levels and LDL particles of higher density with decreased ratios of core-to-surface components. Apoprotein B/E receptor-mediated binding of LDL to hepatic membranes was twofold higher for animals fed the CO-based diet. Animals fed the OL-based diet had lower hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity and increased levels of hepatic cholesterol. Hepatic cholesteryl ester levels were lowest for animals fed the lard-based diet. Increasing dietary fat quantity resulted in increased plasma LDL levels and hepatic cholesterol, HMG-CoA reductase activity and receptor affinity for LDL. No changes were observed in LDL binding. These data demonstrate that, independent of dietary fat quantity, CO-based diets lower plasma LDL levels, modify LDL composition and increase hepatic apoprotein B/E receptor number.     

Maternal and perinatal magnesium restriction predisposes rat pups to insulin resistance and glucose intolerance

According to the fetal programming hypothesis, impaired intrauterine development results in insulin resistance and associated metabolic disturbances. Recently, we reported increased body fat, a forerunner of insulin resistance, in the pups of mineral-restricted rat dams. To identify the causative mineral(s), the effect of magnesium restriction was assessed. Female weanling WNIN rats (n = 21) consumed ad libitum for 9 wk a 70% magnesium-restricted diet or were pair-fed a control (C) diet (n = 7). After 9 wk, they were mated with control males. Control dams and pups were fed the control diet throughout, whereas 7 Mg-restricted dams were switched to the control diet at parturition and their pups weaned onto the control diet (RP). Pups of the remaining 14 restricted dams were weaned onto the control diet (RW) or the Mg-restricted diet (R). All groups had 8 male pups from weaning. Pups were studied on postnatal d 90 and 180. R pups weighed less than C pups at weaning, but both RP and RW pups caught up with controls by d 90. At this time, R pups were neither insulin resistant nor glucose intolerant, but had a higher percentage of body fat and plasma triglycerides and lower lean body and fat-free mass than C pups. These variables were partially corrected in both RP and RW pups. On postnatal d 180, R, RP, and RW pups were insulin resistant and had a lower insulin response to a glucose challenge than C pups; however, glucose tolerance was impaired only in RW pups. Thus, maternal magnesium restriction irreversibly increases body fat and induces insulin resistance in pups by 6 mo of age, whereas additional perinatal Mg deficiency impairs glucose tolerance.     

Vitamin A during lactation: relationship of maternal diet to milk vitamin A content and to the vitamin A status of lactating rats and their pups

We have investigated the effects of maternal vitamin A intake during pregnancy and lactation or during lactation alone on the concentration of vitamin A in rat's milk and on vitamin A levels in plasma and liver of dams and their pups. Groups of Sprague-Dawley rats were fed diets having either a high vitamin A content [15 retinol equivalents (R.E.)/g diet] or a low vitamin A content (0.6 R.E./g) for 42 d, including 7-8 d prior to pregnancy, pregnancy, and for 14 d of lactation. The concentration of vitamin A in milk on d 14 of lactation was significantly greater on the high vitamin A diets [114 +/- 16 micrograms/dl (mean +/- SEM; n = 8) versus 52 +/- 7.3 micrograms/dl (n = 11), P less than 0.005]. However, milk vitamin A concentration on d 1 of lactation did not vary with maternal vitamin A intake during pregnancy. In a second study in which supplementation with vitamin A (30 R.E./g diet) was begun on d 1 postpartum, the milk vitamin A content increased progressively with duration of lactation. Maternal plasma vitamin A concentrations did not differ between rats fed the higher or lower vitamin A diets. However, liver vitamin A concentrations both of dams and of their 14-d-old pups were significantly higher when dams were fed the higher vitamin A diets during pregnancy and/or lactation. The results of these studies indicate that the transfer of vitamin A from mother to offspring by milk and the vitamin A status of dams and their suckling neonates is influenced by maternal vitamin A intake during lactation.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of taurine on the cholesterol metabolism in rats fed diets supplemented with cholestyramine or high amounts of bile acid

The effects of taurine on serum cholesterol levels and hepatic cholesterol 7alpha-hydroxylase activity (CYP7A1) were studied in rats fed cholestyramine or high amounts of sodium cholate in order to alter the intestinal pool of bile acids. Rats were fed a diet supplemented with 1% cholesterol and 0.25% sodium cholate (high cholesterol, control; C), and C supplemented with 4% cholestyramine (CH) or 0.75% sodium cholate (BA) for 14 d. Taurine groups were fed the diet supplemented with 3% taurine (CT, CHT and BAT). Compared to rats fed C and BA diets, serum cholesterol levels were significantly reduced in rats fed CT and BAT diets, but a significant reduction of serum cholesterol by taurine feeding was not observed in the CHT group as compared to the CH group. An increase in hepatic CYP7A1 activity due to taurine intake was observed in the CT and BAT groups. However, the simultaneous administration of cholestyramine and taurine (CHT group) did not increase hepatic CYP7A1 activity compared the intake of cholestyramine only (CH group). A significant increase in fecal bile acid excretion due to taurine intake was found only in rats fed the CT diet. In conclusion, it is suggested that taurine facilitates hepatic CYP7A1 activity regardless of the enlarged intestinal pool of bile acids due to increased intake of exogenous bile acid, and then reduces the serum cholesterol concentration.     

Conjugated linoleic acid is a growth factor for rats as shown by enhanced weight gain and improved feed efficiency

We studied the effect of conjugated linoleic acid (CLA) on rat development and growth. Primigravid female Fischer rats were fed control or CLA-supplemented (0.25% or 0.5% CLA) diets during gestation and/or lactation. Conjugated linoleic acid was incorporated into milk fat and tissue lipids proportional to the level of CLA fed and the duration of CLA feeding. Conjugated linoleic acid was incorporated into fetal and neonatal tissues; it did not affect litter size nor induce apparent abnormalities. To the contrary, feeding CLA to the dams during gestation and lactation improved the postnatal body weight gain of pups (P < 0.05), measured on d 10 of lactation. Pups that continued to receive the CLA-supplemented diet after weaning had significantly greater body weight gain and improved feed efficiency relative to control animals (P < 0.05).     

Dietary fat dependence of intestinal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity in rats

The effects of dietary fats on intestinal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity were studied in rats. Animals were fed experimental diets ad libitum for 7-13 d then killed in the morning for the determination of the reductase activity in an epithelial cell homogenate. When corn oil was the source of dietary fat, the specific activity of jejunal reductase depicted a biphasic pattern in response to dietary fat level with a peak activity when the diet contained 10% fat (by weight) whereas the specific activity of ileal reductase was independent of the fat level. Reductase activities were apparently independent of the degree of saturation of dietary fat (safflower oil, olive oil, lard and tallow) when each was fed as 10% of the diet. Both jejunal and ileal reductase activities were higher when trilaurin was fed than when other saturated fats (tricaprylin, trimyristin, tripalmitin and tristearin) were fed. The jejunum synthesized more cholesterol than the ileum. There was no significant correlation among the reductase activity, cholesterol content of the epithelial cells and the rate of fat absorption, suggesting a complex regulatory mechanism.     

A high dietary lipid intake during pregnancy and lactation enhances mammary gland lipid uptake and lipoprotein lipase activity in rats.

Rats fed a diet with high fat concentration produce larger amounts of milk with a higher lipid concentration than rats fed a lower fat diet. This investigation was designed to study the relationship between dietary fat intake, mammary gland lipid uptake and lipogenesis in rat dams fed, during pregnancy and lactation, one of two purified diets, with equal energy density, containing 2.5 (LL) or 20 g fat/100 g diet (HL). Milk lipid concentration and fatty acid composition were determined at d 14 of lactation. Mammary gland lipogenesis, lipoprotein lipase (LPL) activity and the uptake of [1-(14)C]triolein by the mammary gland and its transfer to the pups was measured. The intestinal absorption of oral (14)C-lipid, (14)CO(2) production and the amount of (14)C-lipid transferred to the pups (milk clot + pups carcass) were significantly higher in the HL group than in the LL group (P < 0.05). Mammary gland lipogenesis was 75% lower and LPL activity was 30% higher in the HL group (P < 0.05). Medium-chain fatty acids (C6-C14) excretion was 46% lower and that of long-chain fatty acids was 142% (P < 0.001) higher in the HL group than in the LL group. The higher milk lipid excretion in the rats fed a high-fat diet resulted from a larger uptake of dietary lipid by the mammary gland, indicated by a larger transfer of (14)C-lipid to the pups and by a higher LPL activity in the mammary gland.     

Marginal maternal Zn intake in rats alters mammary gland Cu transporter levels and milk Cu concentration and affects neonatal Cu metabolism

Marginal zinc intake is common and leaves women particularly vulnerable to Zn deficiency due to increased demand for Zn as a consequence of reproduction. Zn deficiency during pregnancy and lactation has been associated with secondary affects on copper metabolism in the offspring; however, the underlying mechanisms are unknown. The effects of marginal maternal Zn intake on maternal and neonatal Cu metabolism were determined in rats. Plasma, milk and tissue Cu and Zn concentrations and plasma and milk ceruloplasmin (Cp) activity were measured in dams fed a control (CON, 25 mg Zn/kg diet) or a marginal Zn diet (ZD, 10 mg Zn/kg diet) and their suckling pups. There was no effect on maternal tissue Cu or Zn or milk Zn concentration; however, plasma Cp activity was higher in dams fed ZD, suggesting that Cp activity may be a useful marker for identifying marginal Zn status. Rats fed ZD had high mammary gland Ctr1, Atp7A and Atp7B levels, milk Cp activity and Cu concentration. Immunostaining and differential centrifugation indicated that ZD also altered Ctr1 and Atp7A localization in the mammary gland. Pups from dams fed ZD had higher small intestine Cu and lower plasma Cu than CON pups. These results suggest that marginal maternal Zn intake during pregnancy and lactation increase mammary gland Cu transporter levels and alter their localization, resulting in high milk Cu levels, possibly in response to transiently elevated plasma Cu levels. The combination of high milk Cu concentration and immature neonatal Cu transport exposes the suckling neonate to excess Cu; however, whether this occurs in humans is not yet known.     

Postnatal selenium repletion protects lungs of neonatal rats from hyperoxia.

We reported previously that Se-adequate neonatal rat pups born to Se-adequate dams were resistant to lung damage by hyperoxia. To assess whether early postnatal Se repletion could also protect developing pups reared under hyperoxia, female Sprague-Dawley rats (n = 20) were bred and fed a Se-deficient (0.04 microgram/g) diet during pregnancy. On d 1 postpartum, dams were divided into two groups and fed either a Se-deficient diet or a Se-repleted (0.5 microgram/g) diet. On d 4 postpartum, litters in each group were randomly assigned to either air or high oxygen (greater than 95% O2) environments. Histologic evaluation of lungs from d-8 pups indicated that Se repletion significantly reduced the incidence of lung lesions caused by hyperoxia. Selenium-repleted pups also had significantly greater lung volumes and internal surface areas. The 7-d period of Se repletion resulted in significantly elevated maternal milk Se concentrations compared with a Se-deficient group, which was reflected in the pups by elevated plasma and hepatic Se concentrations and Se-dependent glutathione peroxidase (SeGPx) activities. Pulmonary glutathione concentration and SeGPx activity in pups were affected by oxygen exposure only, not by Se nutrition. Therefore, early postnatal Se repletion can protect the developing lung from oxygen-induced injury, a protection that is not entirely due to the effects of Se on pulmonary SeGPx activity and glutathione concentration.     

Dietary fat-dependent changes in hepatic cholesterogenesis and the activity of 3-hydroxy-3-methylglutaryl-CoA reductase in fasted-refed rats.

Effects of various dietary fats on the activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and sterol and fatty acid synthesis from [1-14C]acetate and [2-14C]mevalonate were examined in the liver from fasted-refed rats. Rats fasted for 2 days were refed a fat-free diet or diets containing various fats (tricaprylin, trilaurin, trimyristin, tristearin, camellia oil, or safflower oil) at the 10% level for 1, 3, or 7 days. The activity of HMG-CoA reductase was restored to about one-half of the pre-fasting levels in all groups after refeeding for 1 day and increased to above the pre-fasting levels after 3 days, with the exception of safflower oil, the rise was especially noticeable when fat-free, tricaprylin, and tristearin diets were fed. After 7 days, the activity of HMG-CoA reductase, except for rats refed tristearin, was decreased to levels that were far below those observed after 1 day-refeeding. This was particularly marked with tricaprylin, trilaurin, and camellia oil. The response of sterogenesis resembled that of the reductase. Dietary fat-dependent modification of fatty acid synthesis from [1-14C]acetate was first demonstrated after 7 days. Hepatic esterified cholesterol tended to accumulate and the deposition was marked after 3 days of refeeding. However, fat-dependent alterations of this parameter were remarkable on day 7. The concentration of plasma cholesterol also showed dietary fat-dependent changes after refeeding. Dietary fats appear to play an important role not only in the regulation of hepatic HMG-CoA reductase and sterol synthesis, but also in the overall processes of cholesterol dynamics.     

Influence of dietary fiber on lipid metabolism in meal-fed rats

The effects of the four major components of dietary fiber--cellulose, hemicellulose, pectin and lignin--on lipid metabolism were studied in meal-fed Wistar rats maintained on a cholesterol-free semipurified diet for 21 days. Transit time was decreased and fecal weight increased compared to rats fed a fiber-free diet. Rats fed cellulose or lignin gained significantly less weight than rats fed hemicellulose or pectin. The fibers had no effect on serum cholesterol levels, but serum triacylglycerol levels were significantly higher in rats fed cellulose. Liver cholesterol levels were higher in cellulose-fed rats but liver triacylglycerol levels were highest in rats fed hemicellulose or pectin. Hepatic cholesterol 7 alpha-hydroxylase and HMG-CoA reductase activities were highest in rats fed cellulose and pectin, respectively. Epididymal fat cell size was similar in all groups but fat cell number was highest in pectin-fed rats. Perirenal fat cell size was greatest in rats fed cellulose or lignin and fat cell number in rats fed cellulose or hemicellulose. Lipoprotein lipase activity (per 10(6) cells) was elevated in epididymal fat of rats fed pectin and in perirenal fat of rats fed hemicellulose. Carcass lipid accumulation was highest in rats fed cellulose or lignin. Rats fed cellulose accumulated significantly higher levels of carcass cholesterol and triacylglycerol. Of the fibers fed, cellulose led to an accumulation of serum, liver and carcass lipid. The four fibers fed represent purified and altered forms of cellular components and the observed effects cannot be extrapolated to diets containing foods rich in one or another of these components.     

The hypocholesterolemic effect of high amylose cornstarch in rats is mediated by an enlarged bile acid pool and increased fecal bile acid excretion,not by cecal fermented products

Sham-operated and cecectomized rats were fed for 21 d a cholesterol-free purified diet containing (200 g/kg) either normal cornstarch (CS) or high amylose cornstarch (HACS). In both types of rats, those fed the HACS diet had a significantly lower plasma total cholesterol concentration and a significantly larger intestinal bile acid pool than those fed the CS diet. In cecectomized rats, those fed the HACS diet had significantly lower plasma HDL and LDL cholesterol concentrations, a significantly greater fecal bile acid excretion and a significantly lower hepatic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase mRNA concentration than those fed the CS diet. The plasma triglyceride concentration and LDL-receptor mRNA concentration were not affected by the diet or cecectomy. In sham-operated rats, the propionate concentration in the cecal contents was significantly greater in those fed the HACS diet than in those fed the CS diet. Compared with sham-operated rats, cecectomized rats had significantly enhanced cholesterol 7alpha-hydroxylase activity. In intact rats, biliary bile acid flux into the small intestine was significantly greater in those fed the HACS diet than in those fed the CS diet. Thus, the hypocholesterolemic effect of HACS appears to be mediated by accelerated fecal excretion of bile acids and increases in the intestinal pool and biliary flux of bile acids, and not by cecal fermentation products.     

Effects of litter size and diet composition on the development of some lipogenic enzymes in the liver and brown adipose tissue of the rat

Male Sprague-Dawley rats were reared in litters of nine (normal litters) or 18 pups, and the dams were fed either a low fat (control) or a high fat diet. Offspring from each litter size and diet group were separated from the mothers on postnatal d 30, subdivided into two groups each, and fed either the control or the high fat diet until postnatal d 77. Hepatic glucose-6-phosphate dehydrogenase, malic enzyme and ATP-citrate lyase activities in the offspring from large litters were elevated during the early stages of weaning but later lagged behind enzyme activity of the normal litters. Brown adipose tissue enzymes also surged earlier in rats from large litters but did not fall below the values attained by the normal litters until postnatal d 32. Enzyme activities on postnatal d 77 revealed that large litter size and high fat feeding during or after weaning were associated with diminished hepatic enzyme activities. Hepatic glucose-6-phosphate dehydrogenase and ATP-citrate lyase activities also showed significant positive interaction between litter size and diet composition after weaning. Large litter size was also associated with diminished brown adipose tissue enzymes in the mature rats, but the composition of the weaning diet did not independently exert long-lasting changes in this tissue. Nevertheless, there was a positive interaction between litter size and diet composition during and after weaning. The data suggest that neonatal undernourishment can exert a long-term influence on the metabolic profiles of the animal, and that diet plays a role in modulating this influence.