The dependence of the rate of BP metabolism in the rat small intestinal mucosa on the composition of the dietary fat

We studied the effects that dietary fat has on the capacity of preparations of rat small intestinal mucosal cells to metabolize benzo[a]pyrene (BP) in vitro and on the composition of fatty acids in the endoplasmic reticulum of the intestinal mucosa. When rats were fed diets containing different types of fat, there were significant changes in the incorporation of fatty acids into the endoplasmic reticulum of the mucosal cells of the small intestine: the proportions of polyunsaturated fatty acids in the endoplasmic reticulum reflected the amounts of these fatty acids in the dietary fat. The rate of BP oxidation in the intestinal mucosa was dependent on the amount and composition of the dietary fat, but the range and proportions of the metabolites produced were not affected. Dietary C_18:2 was particularly important in elevating the rate of BP oxidation, but dietary C_20:5 and C_22:6 also effectively increased the rate of BP oxidation. The rate of BP oxidation in the small intestine of rats fed different diets was positively correlated with the proportion of polyunsaturated fatty acids in the endoplasmic reticulum of the mucosal cells.     

The TCDD receptor in rat intestinal mucosa and its possible dietary ligands

Induction of aryl hydrocarbon hydroxylase (AHH) by poly cyclic aromatic hydrocarbons and other inducers such as 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) is known to occur following binding of the inducer to a soluble receptor protein similar to steroid hormone receptors. This receptor is usually called the TCDD receptor, since TCDD has the highest affinity of all known ligands for the receptor. In the present paper, a receptor for TCDD in cytosol from rat intestinal mucosa has been studied, using isoelectric focusing in polyacrylamide gel. This receptor's biochemical properties were found to be similar to those of the TCDD‐receptor in rat liver cytosol. The dissociation constant (Kd) of the ³H‐TCDD‐receptor complex in rat intestinal mucosa was 0.7–3.1 nM, and it was present at a concentration of 70–80 fmol/mg protein. Starvation did not significantly increase the receptor level. The affinities of some potential dietary ligands for the TCDD receptor in rat intestinal mucosa were also studied. Indole‐3‐carbinol had 1/2,600 of the affinity of TCDD for the receptor protein. Bu‐tylated hydroxyanisole (BHA), transstilbene oxide and quercetinpentamethylether competed even more weakly with ³H‐TCDDfor binding to the receptor. The biological significance of the occurrence of low‐affinity ligands of dietary origin for the TCDD receptor is uncertain at the present time.     

The impact of dietary fat and fiber on intestinal carcinogenesis

The effect of dietary fiber on intestinal carcinogenesis in animals is controversial. Some find that the addition of wheat bran or cellulose inhibits intestinal cancer in rats, while others report no effect. Such mixed results often are due to differences in the design of experiments. One important aspect in this regard is the amount of fat in the diet. Some fiber supplements inhibit cancer formation when the fat content is normal but not when it is high. However, a recent epidemiological study in Scandinavia showed a lower cancer incidence in a rural population compared with an urban area, in spite of the fact that the dietary fat content was high in both regions. There was a modest difference in the amount of fiber, and this may not have accounted completely for the variation in cancer incidence. Other dietary factors might have added inhibitory response to help overcome the promotional effect of an excessive amount of fat. The interaction among dietary components must be considered when designing animal experiments to assess the effect of fiber on cancer development.     

Effects of dietary pectin and fat on the small intestinal contents and exocrine pancreas of rats

The effects of dietary pectin and fat level on digestive enzyme activities in the pancreas and small intestine and on intestinal bile acid levels were investigated. In unfed rats, dietary pectin did not influence the pancreatic enzymes studied, but a higher level of corn oil in the diet lowered the amylase activity in the pancreas, increased pancreatic lipase activity and slightly lowered the chymotrypsin and trypsin activities. Diet did not change the dry weight of the pancreas. In the fed rats, dietary pectin increased the dry weight of the small gut wash plus the mucosal scraping. Dietary pectin increased the small intestinal lipase and chymotrypsin levels and at the low level of fat only, increased amylase and trypsin activities in the small intestine of fed rats. Intestinal lipase levels were higher and amylase levels lower in rats consuming the high level of corn oil. These results indicate that changes in dietary fat level led to changes in the amylase and lipase content of secreted pancreatic juice and that differences in absorption associated with diets containing pectin could be the result of increased material in the small intestine.     

Effect of dietary fat composition on rat colon plasma membranes and fecal lipids

The present study was designed to examine the effect of dietary fat composition on the structure of colon mucosal plasma membranes and fecal lipids. Rats were fed a purified diet containing 14% of either highly saturated fat (beef fat or butterfat) or highly polyunsaturated oil (safflower) in addition to 2% corn oil for 4 wk. Colon mucosal membranes were prepared and examined for lipid composition and protein pattern. Saturated fatty acid feeding resulted in the loss of some protein bands from plasma membranes compared to feeding polyunsaturated fatty acids. Within the saturated fatty acid--rich fats, feeding beef fat caused a greater loss than did feeding butterfat. Dietary fat composition had no effect on membrane content of phospholipid and cholesterol. Saturated fatty acid feeding resulted in an increase in the percentage of 18:1 in plasma membrane lipids compared to feeding safflower oil. The observed changes in the structure of colon mucosal membrane of animals fed the saturated fats were associated with an increase in fecal free fatty acids. There was a 4-fold and 2-fold increase in fecal free fatty acids with feeding the beef fat and butterfat diets, respectively, compared to the safflower oil diet. Alterations in fecal bile acid and free fatty acid composition were also noticed with feeding saturated fatty acids. The results obtained suggest that feeding saturated fatty acids as the main source of fat in the diet could influence the structure of colon mucosa, and this could be mediated through fecal free fatty acids.     

The influence of dietary fat on mammary tumor metastasis in the rat

Young, virgin female Fischer 344 rats bearing the 13762 transplantable mammary tumor were fed diets containing either 5% (low-fat group) or 23% (high-fat group) corn oil for five weeks before and six weeks after tumor implantation. Animals in the two diet groups gained weight at comparable rates throughout the experiment. There was no significant difference between the low-fat and high-fat groups with respect to average tumor diameter measured twice per week for six weeks. At the time of death (6 weeks after tumor implantation), the lungs of all rats in both diet groups contained some metastatic tumor deposits; the volume of the metastases in the lungs varied widely in both groups. Numbers of metastases to regional lymph nodes and kidneys appeared unaffected by the fat content of the diet. Thus, both growth of the 13762 mammary tumor itself and metastatic spread from the tumor were comparable whether the young rats were fed a high-fat or a low-fat diet.     

The influence of dietary fat on mammary tumor metastasis in the rat

Young, virgin female Fischer 344 rats bearing the 13762 transplantable mammary tumor were fed diets containing either 5% (low‐fat group) or 23% (high‐fat group) corn oil for five weeks before and six weeks after tumor implantation. Animals in the two diet groups gained weight at comparable rates throughout the experiment. There was no significant difference between the low‐fat and high‐fat groups with respect to average tumor diameter measured twice per week for six weeks. At the time of death (6 weeks after tumor implantation), the lungs of all rats in both diet groups contained some metastatic tumor deposits; the volume of the metastases in the lungs varied widely in both groups. Numbers of metastases to regional lymph nodes and kidneys appeared unaffected by the fat content of the diet. Thus, both growth of the 13762 mammary tumor itself and metastatic spread from the tumor were comparable whether the young rats were fed a high‐fat or a low‐fat diet.     

Interactions between hemolytic saponins, bile salts and small intestinal mucosa in the rat

The interaction between bile salts and saponins from Gypsophylla was investigated in vitro, using changes in transmural potential difference across isolated lengths of rat jejunum as an index of the capacity of the saponin to affect the permeability of intestinal mucosal cells. The addition of saponin (ca. 5 mM) to taurocholic acid in buffered saline (pH 7.4) led to a significant increase in viscosity, indicating the formation of a polymer. The viscosity of the solution was highest at low molar ratios of bile salt to saponin (0.5-2.0). Under these conditions there was an inhibition of the permeating effect of saponins on the gut, as judged by the rate of decline in transmural PD. There was no evidence of inflammation or functional damage to the jejunal mucosa of rats fed a diet containing Gypsophylla saponin (ca. 1.5% w/w) for 7 d but changes in villus morphology were observed. There was also evidence of an increased rate of mucosal cell proliferation. Serum cholesterol levels were significantly lower in saponin-fed rats than in controls, while the cholesterol content of the cecal contents was increased. These results suggest that despite the protective effect of bile salts, Gypsophylla saponins interact with the mucosa of the proximal small intestine in vivo, but at the dietary level used in this study the mucosa was protected by an enhanced rate of cell replacement. The loss of cholesterol via exfoliated mucosal cells may contribute to the hypocholesterolemic effect of saponins in rats.     

Influence of dietary fat quantity and composition on insulin binding to rat intestine.

It is presently recommended that the general US population reduce the consumption of dietary lipid in order to reduce the risk of several chronic diseases, although the mechanism(s) through which dietary factors alter cellular function remain unclear. Dietary lipid composition has been shown to alter the plasma membrane lipid composition of adipocytes, muscle and other tissues. These changes in membrane lipid composition have been correlated with altered insulin receptor binding and signal transduction. Insulin receptors are present on mucosal cells of the intestinal tract, although their role in this tissue is not fully understood. We have fed rats diets containing 6, 31.4 or 76% of calories from lard (Protocol 1) and found insulin binding to be increased in the duodenum and decreased in the colon of rats fed the high-fat diet. Additionally, we compared diets containing either 12 or 37.6% of calories from beef tallow (saturated fatty acids or SFA) or corn oil (polyunsaturated fatty acids or PUFA; Protocol 2) and found insulin binding in the jejunum to be significantly decreased by a low SFA or high PUFA diet relative to the low PUFA diet. These results suggest that intestinal insulin receptors are responsive to dietary lipid quantity and quality which may have implications as to the role of dietary factors in modifying nutrient transport and/or risk of intestinal disease.     

The influence of dietary fat on fat metabolism and body fat deposition in meal-feeding and nibbling rats.

1. An experiment was done with rats (body-weight 160 g) to study the effects on fat metabolism and body composition of low (10 g/kg)- or high (140 g/kg)- fat diets fed as one meal for one 4 h period/d (meal-feeders) or as six spaced meals/d (nibblers). The daily energy intake/unit metabolic body-weight (body-weight 0.73) was the same for all four groups, and this level of intake was about 80% of that consumed by rats allowed unrestricted access to the low-fat diet. The experimental period was 76 d. 2. Rats given the high-fat diet deposited more body fat/d and, as a result, grew faster and were energetically more efficient than rats given the low-fat diet depressed de novo lipogenesis from glucose in epididymal and perirenal fat pads, whose fatty acid composition resembled that of the diet. 3. For both diets meal-feeders had greater stomach plus small intestine weights than nibblers and had higher plasma free fatty acid levels, when they were killed 15 h after their last meal. 4. Meal-feeders given the low-fat diet had the greatest rate of lipogenesis for fat pads. 5. Meal-feeders given the high-fat deposited less of the main dietary fatty acids in their fat pads. 6. There was no evidence that meal-feeders eating a high-fat diet adapt their metabolism completely that they become more efficient utlizers than those nibbling this diet. Meal-feeders eating the low-fat diet became no fatter than nibblers of this diet, possibly because they were eating less than their daily ad lib. intake.     

Effect of dietary lactose on salt-mediated changes in mineral metabolism and bone composition in the rat

The effects of salt (sodium chloride) supplementation of rat diets (80 g/kg diet), with or without lactose (150 g/kg), were studied in weanling rats over 14 d. Dietary salt increased water intake and reduced weight gain and food conversion efficiency, but these variables were unaffected by lactose. Salt-supplemented rats exhibited a three- to fivefold increase in urinary calcium excretion and a small increase in urinary magnesium and phosphorus excretion, irrespective of dietary lactose content. In addition, salt supplementation reduced plasma alkaline phosphatase (EC 3.1.3.1) activity. Lactose increased urinary Ca and Mg excretion and plasma Ca and P concentrations. Salt reduced tibia mass but not tibia mass expressed relative to body-weight, but neither variable was affected by lactose. Both tibia Mg content and concentration were reduced by salt but unaffected by lactose, and neither tibia P content nor concentration was affected by salt or lactose. Tibia Ca content was reduced by salt but this was prevented by lactose. Tibia Ca concentration was unaffected by salt or lactose, although there was a reduction (not significant) in tibia Ca concentration in animals fed on the lactose-free diet. These results show that lactose had no independent effect on bone and that reduced accretion of bone mass and mineral content in rats fed on the high-salt diets was due, at least in part, to reduced growth. Failure to offset sodium-induced hypercalciuria by a compensatory increase in net Ca absorption may have contributed to reduced bone Ca accretion. The protective effect of lactose against reduced bone Ca accretion may be due to increased Ca absorption.     

The effect of moderately and severely restricted dietary magnesium intakes on bone composition and bone metabolism in the rat

Forty 3-week-old male rats, Wistar strain, average weight 59 g, were randomized by weight into five groups of eight rats each. Three groups were fed ad libitum on a semi-purified diet containing (per kg) 400 (adequate), 200 (moderately Mg-restricted) or 20 (severely Mg-restricted) mg Mg for 3 weeks while two groups were pair-fed with the Mg-adequate diet in the same quantities as those consumed by the two Mg-restricted groups respectively. While weight gains and food conversion efficiency values for the Mg-restricted groups were similar to those of the corresponding pair-fed control groups, serum and kidney Mg, and femoral dry weight were reduced by 70, 7 and 9% respectively in the severely Mg-restricted group and were unaffected in the moderately Mg-restricted group. Significant reductions were observed in urinary pyridinoline (Pyr) (by 44 and 34%) and deoxypyridinoline (Dpyr) levels (by 40 and 33%) (markers of bone resorption), serum osteocalcin levels (by 46 and 28%) (marker of bone formation), femoral Mg levels (by 52 and 14%) and osteocalcin mRNA levels (by 46 and 22%) compared with the corresponding pair-fed controls, in the severely and moderately Mg-restricted groups respectively, and these reductions, except for those in urinary Pyr and Dpyr, were more marked in the severely Mg-restricted group. Femoral Ca and P concentrations were unaffected by dietary Mg restriction. These results show that not only severe but also moderate dietary restriction of Mg over 21 d results in qualitative changes in bone (i.e. reduced Mg concentration) as well as in aberrant bone turnover in young growing rats (i.e. severely depressed rates of bone formation and bone resorption), which may impair bone development and bone strength.     

矿物质元素和维生素对膳食诱导肥胖大鼠代谢的影响

目的　探讨矿物质元素钙、镁、锌、铁、铬和维生素A、B1、B2、C、D、E对膳食诱导肥胖大鼠代谢影响。方法　利用高能饲料诱导大鼠肥胖模型后 ,观察部分矿物质营养素钙、镁、锌、铁、铬和维生素A、B1、B2、C、D、E对肥胖大鼠代谢的影响。血糖采用试纸法测定 ;应用酶法测定血脂 ;放射性免疫法测定胰岛素、瘦素的含量。结果　B组体重和脂体比显著高于其它各组 ,D组和E组体重增加的趋势明显降低 ,二者较接近且略高于A组 ,C组在实验中后期体重的持续下降可能与机体必需的矿物质元素和维生素长期摄入不足有关 ,而非生理状态下的减重 ,其各项代谢指标均出现下降 ;无论血糖、血脂、胰岛素还是瘦素 ,与E组相比 ,D组都有更明显的降低趋势。结论　膳食矿物质元素钙、镁、锌、铁、铬和维生素A、B1、B2、、C、D、E对肥胖大鼠体重和体脂含量没有更明显的减低作用 ,但可以有效地降低肥胖大鼠的高血糖和高血脂 ,改善高胰岛素血症和高瘦素血症 ,纠正了肥胖大鼠物质和能量代谢的失衡     

The effect of vitamin D3 and dietary calcium level on the cadmium-induced morphological and biochemical changes in rat intestinal mucosa.

The effect of vitamin D3 and dietary calcium level on the cadmium-induced changes was observed in the duodena of rats raised on various diets differing in vitamin D and calcium levels. Observation with scanning electron microscopy revealed that vitamin D and dietary calcium were required for normal intestinal villi and microvilli formation. The damaged cells were observed in the intestinal villi of cadmium-exposed rats. Furthermore, dietary cadmium reduced the enzyme activities in microvilli. Especially, alkaline phosphatase activity was reduced in the cadmium-exposed groups, even though it was still responsive to vitamin D3. These effects with cadmium were modulated by vitamin D3 and dietary calcium level. That is, in the presence of vitamin D3 and calcium, the effect of cadmium on intestinal villi and microvilli was reduced.     

Rat small intestinal morphology and tissue regulatory peptides: effects of high dietary fat.

Sprague-Dawley rats (3 weeks old) were fed on isoenergetic diets in which 40% of the total energy was provided as fat either in the form of butter (high saturated fat), olive oil (high monounsaturated fat) or maize oil (high polyunsaturated fat), with one group on low-fat (10% of total energy) standard diet as a control. Animals were killed after 8.4 (se 0.8) weeks by cardiac puncture. Similar pieces of jejunum and ileum were prepared for morphometric studies. Extracts of tissue from the proximal and distal segments of the whole small intestine from four animals per group were assayed using established techniques for enteroglucagon, motilin, neurotensin, somatostatin, substance P and vasoactive intestinal peptide (VIP). We found that maize oil and olive oil increased villus height: crypt depth ratio in both jejunum and ileum. Maize oil increased tissue concentrations of somatostatin (P less than 0.05) and substance P (P less than 0.005) in the proximal segment. Both maize oil and olive oil increased tissue concentrations of neurotensin and substance P (P less than 0.005) in the distal segments. These observations may explain the improvement of intestinal absorption of fluid following supplementation with polyunsaturated fat.