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Kinetics of viral replication in experimental rotavirus infection: effects of high dietary fat.

Epidemiological studies suggest that dietary fat can affect the frequency and severity of diarrhoeal illnesses in childhood. To study the effects of dietary fat on the kinetics of rotavirus antigen, 3-week-old mice of rotavirus-seronegative mothers were fed isocaloric diets with 40% of the total calories as fat [either butter (high saturated fat), olive oil (high monounsaturated fat), or corn oil (high polyunsaturated fat)] with one group on low fat (10% of calories) standard diet as controls. Seven-day-old mice from the first litter were killed and their stomach contents (milk) analyzed for total fatty acids. Seven-day-old mice from the second litter were inoculated with EDIM rotavirus, and some were killed at 48 h and others at 120 h postinoculation. The stool was removed from the distal colon of each mouse and examined for evidence of diarrhoea. The small intestine was removed, the contents washed, and the intestine divided into equal thirds. All stool and tissue samples were made to 10% (wt/vol), homogenised, and tested for rotavirus antigen by ELISA. We found that (a) dietary fat markedly altered the fatty acid profile of milk, (b) high saturated dietary fat (butter) delayed the onset of diarrhoea, reduced the excretion of rotavirus antigen in stool, and reduced mucosal antigen in the lower third of the small intestine at 120 h compared to 48 h postinoculation, (c) high polyunsaturated dietary fat initially increased the frequency of diarrhoea and viral antigen in the middle and lower segment at 120 h, followed by a reduction in rotavirus excretion in stool.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dietary fats modulate the regulatory potential of dietary cholesterol on cholesterol 7 alpha-hydroxylase gene expression.

Cholesterol 7 alpha-hydroxylase (cyp7) is the rate-limiting enzyme in bile acid biosynthesis. Previously, dietary cholesterol was shown to induce cyp7 gene expression. However, recent studies have produced data that are inconsistent with this observation, suggesting the possibility that other factors in the diet are also important in the regulation of cyp7 by dietary cholesterol. The effect of dietary fats on the ability of dietary cholesterol to regulate cyp7 activity and mRNA abundance was assessed. High fat diets composed primarily of polyunsaturated (PUFA), monounsaturated (MUFA), or saturated (SFA) fatty acids induced hypercholesterolemia regardless of whether cholesterol was present or not. However, the effects of each diet on bile composition and hepatic cholesterol content were variable. Microsomal fatty acid profiles reflected the fatty acid composition of the diets. Addition of cholesterol to the PUFA diet increased cyp7 mRNA abundance and activity, analogous with the results observed in mice fed a chow plus cholesterol diet. On the other hand, addition of cholesterol to diets high in MUFA or SFA caused a significant reduction of cyp7 mRNA abundance and activity. Addition of cholesterol to all the diets caused the expected changes in low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA abundance but was not correlated with the changes in cyp7 mRNA abundance. The relationship between cyp7 mRNA abundance and hepatic total cholesterol content or hepatic microsomal cholesterol content was evident, suggesting that cholesterol status does not necessarily determine cyp7 mRNA abundance. The results of this study illustrate that the type of dietary fat is important in elaborating the regulatory potential of dietary cholesterol on cyp7 gene expression and suggest that the regulation of cyp7 gene expression does not involve the classical sterol-mediated pathway.

Animals↗

Dietary fat consumption and health.

Dietary Guidelines have emerged over the past 30 years recommending that Americans limit their consumption of total fat and saturated fat as one way to reduce the risk of a range of chronic diseases. However, a low-fat diet is not a no-fat diet. Dietary fat clearly serves a number of essential functions. For example, maternal energy deficiency, possible exacerbated by very low-fat intakes (< 15% of energy), is one key determinant in the etiology of low birth weight. The debate continues over recommendations for limiting total fat and saturated fatty acid intake in children. Recent evidence indicates that diets with adequate energy providing less than 30% of energy from fat are sufficient to promote normal growth and normal sexual maturation. More attention needs to be devoted to the effect of dietary fat reduction on the nutrient density of children's diets. The association between dietary fat and CHD has been extensively studied. Diets high in saturated fatty acids and trans fatty acids increase LDL cholesterol levels, and in turn, the risk of heart disease. The relationship between high-carbohydrate/low-fat diets and CHD is more ambiguous because high-carbohydrate diets induce dyslipidemia in certain individuals. Obesity among adults and children is now of epidemic proportions in the United States. High-fat diets leading to excessive energy intakes are strongly linked to the increasing obesity in the United States. However, the prevalence of obesity has increased during the same time period that dietary fat intake (both in absolute terms and as a percentage of total dietary energy) has decreased. These trends suggest that a concomitant decrease in total dietary energy and modifications of other lifestyle factors, such as physical activity, also need to be emphasized. Obesity is also an independent risk factor for the development of diabetes. The current availability of fat-modified foods offers the potential for dietary fat reduction and treatment of the comorbidities associated with diabetes. However, to date, few studies have documented the effectiveness of fat-modified foods as part of a weight loss regimen or in reduction in CHD risks among individuals with diabetes mellitus. The association between total dietary fat and cancer is still under debate. While there is some evidence demonstrating associations between dietary fat intake and cancers of the breast, prostate, and colon, there are serious methodologic issues, including the difficulty in differentiating the effects of dietary fat independent of total energy intake. Reported total fat and saturated fatty acid intakes as a percentage of total energy have been declining over the past 30 years in the United States. Despite this encouraging trend, the majority of individuals--regardless of age--do not report consuming a diet that meets the levels of fat and saturated fatty acids recommended by the Dietary Guidelines for Americans. On a relative basis, saturated fat intake has gone down less than has total fat intake. Individuals of all ages who report consuming a diet with < or = 30% of energy from fat consistently have lower energy intakes. Given the increasing rates of obesity in the United States at an earlier and earlier age, dietary fat reduction may be an effective part of an overall strategy to balance energy consumption with energy needs. In each of the age/gender groups reporting consumption of < or = 30% of energy from fat and less than 10% of energy from saturated fatty acids, fat-modified foods play a more important role in their diets than for people who are consuming higher levels of fat and saturated fat. The data are clear than fat-modified foods make a more significant contribution to diets of consumers with low-fat intakes. While one cannot argue cause and effect from the results presented, the patterns of fat-modified foods/low-fat intakes are consistent. The focus on overall diet quality is often lost in the national obsession with lowering fat inta

Adult↗

How much dietary fat in therapeutic nutrition?

Dietary fat has a less prominent role in realimentation than the alternate source of energy, carbohydrate. Presently available therapeutic diets, in typical feeding routines, provide only 3 to 120 g of fat per day. Three major factors contribute to fat underutilization: long-standing belief that fat is to blame for various vague symptoms of indigestion, misconception that daily fecal fat in excess of 7 g represents bowel dysfunction, and fear of fat-induced atherogenesis. None of these apply to refeeding starved and malnourished patients. The small intestine has a vastly underutilized capacity for fat absorption, and at the habitual fat intake of 100 g per day absorption is complete in the proximal one fifth of the gut. In patients requiring vigorous realimentation, the remaining small intestine should also be utilized. Dietary fat is well tolerated, and daily intakes of 500 g of polyunsaturated fat in a complete diet have not been associated with important side effects, while there was a significant improvement in body stores of fat and protein. Compared to diets high in carbohydrate, adequate intake of fat results in better nutrient utilization, less CO2 production and decreased lipogenesis and insulin requirements. Diets higher in fat are also better tolerated because of their lower volume and osmolality. The result is more effective absorption of calories and a faster nutritional recovery. Increased adipose tissue and protein reserve benefits patients who are in stress, immunocompromised, or debilitated. Adequate dietary fat should be considered for malnourished subjects with intact gastrointestinal function, and when intestinal absorptive capacity is reduced by surgery or disease.

Dietary Fats↗

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.

Administration, Oral↗

Effect of 347-serine mutation in apoprotein A-IV on plasma LDL cholesterol response to dietary fat.

Lipid response to dietary fat and cholesterol is, to a large extent, genetically controlled. Apoprotein (apo) A-IV has been related to fat absorption and to the activation of some of the enzymes involved in lipid metabolism. One mutation has been described in the apo A-IV gene that causes substitution of Ser for Thr at position 347. To study the influence of this mutation on the plasma LDL cholesterol (LDL-C) response in diets of various fat content and fatty acid saturation, 41 healthy male subjects were studied, 25 of whom were homozygous for the Thr allele (347Thr) and the rest who were either homozygous (n = 2) or heterozygous carriers of the Ser allele (347Ser). They consumed three consecutive diets, each of 4 weeks' duration: one rich in saturated fat (SFA diet: 38% fat, 20% saturated), a National Cholesterol Education Program (NCEP) type 1 diet (28% fat, 10% saturated), and a third rich in monounsaturated fat (MUFA diet; 38% fat, 22% monounsaturated). Carriers of the 347Ser allele presented a greater decrease in total cholesterol (-0.7 vs -0.44 mmol/L, P < .034), LDL-C (-0.62 vs -0.31 mmol/L, P < .012), and apo B (-14 vs -8 mg/dL, P < .01) levels when they were switched from the SFA to the NCEP type 1 diet than homozygous carriers of the 347Thr allele. The change from the NCEP type 1 to the MUFA diet resulted in a greater increase in total cholesterol (0.18 vs -0.05 mmol/L, P < .028) and apo B (5 vs -1 mg/dL, P < .006) levels in the 347Ser than in the 347Thr individuals. In a previous study, we demonstrated that the G-->A polymorphism at position -76 of the gene promoter of apo A-I affects the LDL-C response to dietary fat. We therefore decided to study the effect of the interaction between these mutations on this response. We found that both mutations have an additive effect on total cholesterol, LDL-C, and apo B dietary-induced changes. Our results suggest that total cholesterol and LDL-C response to dietary fat is influenced by the 347Ser mutation of apo A-IV.

Adult↗

Clinical trials of altering dietary fat intake.

Alterations of dietary fat that reduce serum cholesterol are beneficial to people who have the highest risk of death from coronary heart disease (CHD). For other people the benefits are less clear; there is a suggestion (hotly disputed) that cholesterol-lowering by drugs, and possibly by diet, increases the risk of non-CHD death, for reasons that are not understood. Furthermore, fat intake interacts with other dietary and non-dietary factors. The consequences of altering dietary fat seem to be more complex and uncertain than have hitherto been supposed.

Cholesterol↗

The postingestive consequences of fat condition preferences for flavors associated with high dietary fat.

To investigate whether children acquire conditioned preferences for flavors associated with high dietary fat content, 27 3- and 4-year-old children participated in a series of 12 conditioning or mere exposure sessions. Following an overnight fast, children who participated in conditioning trials consumed fixed quantities of a flavored yogurt drink that on half the days was high in fat and energy (954 kJ, 18 g fat/150 g serving) or contained no fat (277 kJ, 0 g fat/150 g serving). Children in the conditioning group consumed 150 g servings, children in the mere exposure group tasted 16 g or less of these same stimuli. Preferences were assessed before and after conditioning when the children were hungry and also postconditioning when the children were satiated. Results provided evidence for conditioned preferences based on the postingestive consequences of dietary fat. Children in the conditioning group learned to prefer the high-density paired flavor over the low-density paired flavor, and increased their preference for the high-density paired flavor from pre- to postconditioning. Children in the mere exposure group showed positive shifts in preference for both the fat-free and the high-fat paired flavors. In the conditioning group, preferences for the high-fat flavor was depressed by satiety, whereas the preference of the mere exposure group did not vary with hunger state. Conditioned flavor preferences, based on the postingestive consequences of fat intake, may contribute to children's preferences for foods high in dietary fat.

Association Learning↗

Dietary fats and cancer.

Evidence relating dietary fat to cancer at sites such as the breast and colon is provided by experiments showing that animals fed high-fat diets develop cancer at these sites more readily than do animals fed low-fat diets and by epidemiological data from different countries showing strong positive correlations between cancer incidence and mortality, and level of dietary fat. Experiments on animals have indicated that polyunsaturated vegetable oils promote cancer more effectively than do saturated fats or polyunsaturated fish oils, whereas in the epidemiological data, total dietary fat correlates with cancer incidence and mortality at least as well as does any particular type of fat. Case-control and cohort studies have not shown strong indications of a relationship between dietary fat and cancer, perhaps because of methodological difficulties inherent in such studies. The weight of evidence continues to indicate that long-term adherence to a low-fat diet can reduce the risk of some common types of cancer.

Animals↗

Insulin action in rats is influenced by amount and composition of dietary fat.

The chronic influence of dietary fat composition on obesity and insulin action is not well understood. We examined the effect of amount (20% vs 60% of total calories) and type (saturated vs polyunsaturated) of fat on insulin action and body composition in mature male rats. Six months of feeding a high fat (HF) diet led to obesity and impaired insulin action (determined by a euglycemic-hyperinsulinemic clamp), neither of which were reversed by a subsequent 6 months of feeding a low fat (LF) diet. Within HF fed rats, type of fat did not affect body composition or insulin action. Six months of feeding a low fat diet led to only a slight decline in insulin action, with no difference due to type of dietary fat. From 6-9 months, insulin action became more impaired in LF rats fed the saturated diet than in LF rats fed the polyunsaturated diet. By 12 months, all groups were obese and had a similar impairment in insulin action. The amount and type of fat in the diet did not influence the overall degree of impairment in insulin action but did affect the time course. Both feeding a high fat diet and feeding a low fat saturated diet accelerated the impairment in insulin action relative to rats fed a low fat polyunsaturated fat diet.

Adipose Tissue↗

The influence of dietary fat on insulin resistance.

Dietary fat has been implicated in the development of insulin resistance in both animals and humans. Most, although not all, studies suggest that higher levels of total fat in the diet result in greater whole-body insulin resistance. Although, in practice, obesity may complicate the relationship between fat intake and insulin resistance, clinical trials demonstrate that high levels of dietary fat can impair insulin sensitivity independent of body weight changes. In addition, it appears that different types of fat have different effects on insulin action. Saturated and certain monounsaturated fats have been implicated in causing insulin resistance, whereas polyunsaturated and omega-3 fatty acids largely do not appear to have adverse effects on insulin action. Given the importance of insulin resistance in the development of diabetes and heart disease, establishing appropriate levels of fat in the diet is an important clinical goal.

Dietary Fats↗

Proliferative activity of murine mammary epithelium as affected by dietary fat and calcium.

Dietary fat and calcium have been found to affect significantly the proliferative status of the mammary glands. Female mice (3-week-old C57BL/6J) were given either a low or high corn oil diet (3 or 30% by weight). One, 2, or 4 weeks after the dietary intervention the animals were given injections of [3H]thymidine and/or colchicine; 2 h later their thoracic mammary glands were removed and processed for histology and autoradiography. Animals on the high corn oil diet had an increased labeling index of both terminal ducts and mature ducts compared to the control group at each time (i.e., 10.1 +/- 2.1 versus 4.8 +/- 0.9% at 2 weeks). This effect of a high corn oil diet was evident on the mammary glands of animals at various ages. Animals on a high beef tallow diet also had a high labeling index. This effect of a high fat diet appeared to be reduced by dietary calcium. The labeling index for terminal ducts of animals on high corn oil diet decreased from 14.1 +/- 3.8, 11.9 +/- 3.4 to 8.5 +/- 1.8 and high beef tallow from 13.6 +/- 3.6, 11.4 +/- 0.7 to 9.5 +/- 1.3 for calcium levels of 0.1, 0.5, and 1.0%, respectively. Mitotic indices followed the same trend. These studies demonstrate that a high fat diet affects the proliferative status in the mouse mammary glands in a short period of time and that this effect can be reduced by dietary calcium.

Age Factors↗

Lipid accumulation and body fat distribution is influenced by type of dietary fat fed to rats.

The amount of fat in the diet is known to influence body weight and body composition, but it is not clear whether dietary fat composition can affect body composition independently. We studied the effects of six months of feeding diets containing lard (L), corn oil (CO), fish oil (FO) or medium chain triglycerides (MCT) on body weight and body composition in adult male Wistar rats. Although FO fats ate slightly less total energy than the other groups, there were no differences among groups in body weight at any time during the study. However, body composition, the composition of depot triglyceride, body fat distribution and insulin resistance were all influenced by the type of fat in the diet. FO rats had less total body fat, less intra-abdominal fat, and less insulin resistance than all other groups. Although some of these metabolic effects may have been secondary to a slightly lower energy intake, we believe these data demonstrate the potential impact which dietary fat composition can have on metabolism and body weight regulation.

Adipose Tissue↗

Serum estrogens and estrogen responsiveness in 7,12-dimethylbenz[a]anthracene-induced mammary tumors as influenced by dietary fat.

The effect of dietary fat on mammary tumor incidence, estrogen-binding capacity as related to the hormone dependency of the tumors, and circulating estrogen levels in Sprague-Dawley rats given an oral dose of 7,12-dimethylbenz[a]anthracene (DMBA) was investigated. Rats were fed diets consisting of 0.5, 5, or 20% corn oil starting at weaning and were administered 5 mg DMBA at 50 days of age. Tumor incidences were 13, 46, and 75% for the groups given 0.5, 5, and 20% fat, respectively, when the experiment was terminated 20-22 weeks later. Serum estradiol, measured at proestrus at 50 days of age and at the end of the experiment, was slightly depressed at both time points in rats fed the 0.5% fat diet but was similar in the other 2 groups. Serum estrone levels were not significantly different at either time point. Estrogen receptor levels in the tumor were the same in the groups given 5 and 20% fat but were lower in the group given 0.5% fat. No difference was detected in the progesterone receptor concentrations. Furthermore, most (approximately 70%) of the tumors in all 3 dietary groups regressed in response to ovariectomy, which suggested that dietary fat has very little influence on the estrogen dependence of the tumor. This observation suggested that fat intake does not result in any intrinsic difference in the biochemical action of estrogen.

9,10-Dimethyl-1,2-benzanthracene↗

Regulation of hamster hepatic microsomal triglyceride transfer protein mRNA levels by dietary fats.

The effect of dietary fat on hepatic microsomal triglyceride transfer protein(MTP) large subunit mRNA levels in the hamster was examined. Increasing the dietary fat concentration from 11.7 energy % to 46.8 energy % caused a 60% increase in hepatic MTP mRNA; this increase was shown to be dose-dependent (r = 0.688 p = 0.0023). MTP mRNA levels correlated significantly with several plasma lipoprotein cholesterol parameters. No significant relationship was observed between MTP mRNA and either plasma or VLDL triglyceride. The nature of the dietary fatty acids also influenced MTP mRNA levels, with trimyristin and tripalmitin enriched diets significantly elevating MTP mRNA relative to diets enriched in triolein and trilinolein.

Animals↗

[Contamination and secondary reactions in the processing of dietary fats].

The contamination of dietary fats and oils can have various origins: contamination of the raw materials that could not be eliminated by the industrial process; refining completely eliminates this type of contamination; contamination with one of the processing aids can occur if the process is not properly conducted; contamination with packaging materials will increase with the storage duration of the finished product (in the case of vinyl chloride monomer and styrene contamination); only the strict control and adequate choice of the materials and packaging conditions will allow complete elimination of this contamination type. The presence of small amounts of another fat (in vegetable margarines for instance) should also be mentioned although it is not a real contamination. The secondary reactions that may occur during the processing of dietary fats are primarily due to unwanted chemical reactions leading to the formation of fatty acid or native glyceride isomers (e.g. formation of geometric isomers during deodorization, formation of position isomers during hydrogenation). In the present stage of knowledge, it is fairly easy to avoid secondary reactions during deodorization, those that take place during hydrogenation are not yet under control, however.

Chemical Phenomena↗