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Effect of varying proportions of dietary fat on the development of N-nitrosomethylurea-induced rat mammary tumors.

The influence of diets varying in their relative proportions of dietary fat on N-nitrosomethylurea (NMU)-induced mammary tumorigenesis, was assessed. Animals were initiated on day 50 of age with 25 mg/kg NMU and then placed on casein-based AIN-76A diets containing 5, 10, 16 and 23% corn oil (wt/wt). There were 30 animals/group and the experiment was terminated 22 weeks post-NMU. It was found that animals fed diets containing 16 and 23% corn oil exhibited tumor incidences between 2 and 3 times that of animals fed diets containing 5 and 10% corn oil. No differences in tumor incidence could be detected between the 5 and 10% groups or the 16 and 23% groups, suggesting that a threshold occurs at some point between 10 and 16% fat (or 20 and 33% of total calories as fat). The results of this study suggest that the tumor-promoting effects of dietary fat are manifested in terms of a threshold, rather than a linear dose-response effect.

Animals↗

Down-regulation of PLK3 gene expression by types and amount of dietary fat in rat colon tumors.

Epidemiological studies suggest that high intake of dietary fat rich in saturated fatty acids increases the colon cancer risk whereas dietary fish oil high in omega-3 fatty acids reduces the colon cancer risk. Previously, we reported that consumption of omega-6 fatty acid rich diets such as corn oil strongly promotes azoxymethane (AOM)-induced colon carcinogenesis in rats as compared to ingestion of a diet with equivalent amount of fat containing fish oil (HFFO) or low-fat diet (LFCO). Expression of PLK3 (Polo-like kinase-3, previously named Prk) is negatively correlated with the development of certain cancers. Ectopic expression of human PLK3 results in cell cycle arrest or induces apoptosis. To understand the role of PLK3 in colon carcinogenesis and to study the effect of types and amount of dietary fat on the expression levels of PLK3 in colon tumors, we analyzed the colon tumors and mucosa of rats administered the diets containing fish oil and corn oil for PLK mRNA expression. Here we report that expression of PLK3 was down-regulated in rat colon tumors. Quantitative polymerase chain reaction demonstrated that PLK3 mRNA levels were significantly lower in carcinogen (azoxymethane)-induced rat colon tumors than their uninvolved normal colonic mucosa. Among the normal mucosa isolated from rats fed on diets with various levels of fat (LFCO, or high fat diet with corn oil, HFCO, or supplemented with fish oil, HFFO), no significant changes in PLK3 mRNA expression was detected. Tumors isolated from rats fed with HFCO diet contained a very low level of PLK3 mRNA expression. Interestingly, tumors from rats fed the HFFO diet did not exhibit as dramatic down-regulation of PLK3 as the tumors of animals fed the HFCO diet. Furthermore, our results also indicate that the ectopic expression of a kinase active PLK3 construct induced apoptosis in HT-29 colon carcinoma cells. These observations suggest for the first time that a decreased activity of PLK3 may play a key role in colon tumor development as well as in HFCO-induced colon tumorigenesis.

Animals↗

Augmentation of dietary fat preference by chronic, but not acute, hypercorticosteronemia.

Numerous studies have documented a role for corticosterone in appetitive behavior, including caloric intake and dietary fat preference. In the present study, we have examined the mechanism(s) underlying modulation of dietary fat preference by corticosterone. The results of these studies show a) an increased fat preference with increased basal urinary output, or decreased stimulation of corticosterone output on fasting, b) elevation of fat preference following chronic, but not acute, hypercorticosteronemia produced by exogenous corticosterone administration, and c) emergence of hypercorticosteronemia prior to the development of increased fat preference in developing rats. These observations have led us to suggest that increased fat preference after chronic hypercorticosteronemia may be secondary to changes in the levels or actions of agents known to affect fat intake.

Animals↗

Sensory acceptability of meat and dairy products and dietary fat in male collegiate swimmers.

This study was undertaken to determine whether high-level training alters food choice behavior with regard to meat and dairy products because of their high fat content. Twenty male collegiate swimmers were compared to 20 male sedentary students for dietary fat intake, nutrition knowledge, and liking of meat and dairy products. There was no significant difference between the two groups for restraint, energy intake, dietary fat intake, and energy derived from fat. Nutrition knowledge, energy derived from saturated fat, and cholesterol intake, however, were significantly higher in the athletes. The two groups did not differ in their hedonic ratings of flavor or in their overall degree of liking of the meat and dairy products, and the athletes actually liked the appearance and texture of the products significantly more than did the sedentary students. This study shows that the sensory appeal of fat-containing animal products is not affected in male swimmers by a high level of exercise.

Adult↗

Studies in man of partially absorbed dietary fats.

A saturated long-chain triglyceride (SLCT) has been prepared by esterification with glycerol of the saturated long-chain fatty acid fraction of coconut oil, isolated by molecular distillation of the hydrolyzed oil. The resultant SLCT is comprised principally of stearate (89%) and palmitate (11%). The intestinal absorption of SLCT in man was compared with that of corn oil or a 1:1 mixture of SLCT and corn oil. Each fat or the mixture was incorporated in isocaloric amounts into a complete formula diet deriving 30% of its caloric content from fat, 55% from carbohydrate (dextrose), and 15% from protein (casein). The formula diets were administered in sequential feeding periods as the sole source of food. The results indicate that SLCT was poorly absorbed (31 to 39%) compared with virtually complete absorption of corn oil (98%). Fat absorption was improved when the dietary fat was an equal mixture of SLCT and corn oil. The poor absorption of SLCT was ascribed to its high melting point and related to impaired emulsification and micellar solubilization in the small intestine.

Dietary Fats↗

Effect of dietary fat and lactation status on insulin binding to bovine milk fat globule membranes.

Lactating cows were used to examine the relationship between lactation status and insulin binding to milk fat globule membranes. Variables evaluated were daily milk yield, stage of lactation, breed, age, lactation number, daily milk fat and protein yields, milk fat and protein percentages, breeding status, body weight, body weight.75, and mammary health. Milk yield was correlated with insulin binding and accounted for 20% of the binding variability. No other variables were related to insulin binding. Insulin binding to milk fat globule membranes increased with supplemental dietary fat up to 4% added fat in the diet dry matter. Milk fat globule membranes may provide a useful model for assessing insulin receptor regulation in the mammary gland. Sources of variation in insulin binding to mammary membranes remain to be identified.

Animals↗

Interactions of dietary fats and proteins on fatty acid composition of immune cells and LTB4 production by peritoneal exudate cells of rats.

The interaction of dietary fats and proteins on lipid parameters of rats was studied using safflower oil (linoleic acid-rich), borage oil (gamma-linolenic acid-rich) or perilla oil (alpha-linolenic acid-rich) in combination with casein or soybean protein. The experiment was focused on the fatty acid composition of immune cells and the leukotriene B4 production by peritoneal exudate cells. Serum total cholesterol, triglyceride, and phospholipid levels were low in perilla oil-fed or soybean protein-fed rats. Fatty acid compositions of serum and liver phospholipids reflected those of dietary fats. However, feeding borage oil resulted in a marked increase in the proportion of dihomo-gamma-linolenic acid in phospholipids of peritoneal exudate cells, spleen lymphocytes, and mesenteric lymph node lymphocytes in relation to those of liver and serum. It is suggested that activities of metabolic n-6 polyunsaturated fatty acids are different between immune and other tissues. In addition, the magnitude of the reduction of the proportion of linoleic acid of perilla oil in immune cells was considerably more moderate than serum and liver, indicating a different degree of interference of alpha-linolenic acid with linoleic acid metabolism. Leukotriene release from peritoneal exudate cells was in the order of safflower oil > borage oil > perilla oil groups as reflecting the proportion of arachidonic acid, and tended to be lower in soybean protein-fed groups. These suggest an anti-inflammatory property of gamma-linolenic acid as well as alpha-linolenic acid tended to be strengthened when they were combined with soybean protein than with casein.

Animals↗

Dietary fat and incidence of type 2 diabetes in older Iowa women.

OBJECTIVE: To examine the associations between reported intakes of dietary fat and incident type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied the relation between dietary fatty acids and diabetes in a prospective cohort study of 35,988 older women who initially did not have diabetes. Diet was assessed with a food frequency questionnaire at baseline, and 1,890 incident cases of diabetes occurred during 11 years of follow-up. RESULTS: After adjusting for age, smoking, alcohol consumption, BMI, waist-to-hip ratio, physical activity, demographic factors, and dietary magnesium and cereal fiber, diabetes incidence was negatively associated with dietary polyunsaturated fatty acids, vegetable fat, and trans fatty acids and positively associated with omega-3 fatty acids, cholesterol, and the Keys score. After simultaneous adjustment for other dietary fat, only vegetable fat remained clearly related to diabetes risk. Relative risks across quintiles of vegetable fat intake were 1.00, 0.90, 0.87, 0.84, and 0.82 (P = 0.02). Diabetes risk was also inversely related to substituting polyunsaturated fatty acids for saturated fatty acids and positively correlated to the Keys dietary score. CONCLUSIONS: These data support an inverse relation between incident type 2 diabetes and vegetable fat and substituting polyunsaturated fatty acids for saturated fatty acids and cholesterol.

Age Factors↗

Plasma factor VII is activated by postprandial triglyceridaemia, irrespective of dietary fat composition.

Nine adults took two 7-day diets of standardised energy and total fat content, but with a dietary polyunsaturated/saturated fat ratio of less than 0.3 and greater than 3.0 respectively, while adhering to their daily routine. Blood was drawn on 6 occasions between 09.00 and 22.45 h on the final day of each dietary period for factor VII activity (VIIc), factor VII antigen (VIIag) and lipoprotein lipid concentrations. Diurnal variation was described for each variable in terms of its deviation from the individual's daily mean value at each time point across the day. Plasma triglyceride remained low until after the midday meal, whereafter a marked rise was sustained into the later evening. Plasma VIIc declined until early afternoon, but showed a marked rise in the late afternoon. Plasma VIIag showed no significant diurnal variation. Changes in plasma triglyceride concentration during the day were related positively to changes in VIIc about 160 min later, but not to VIIc at other time points. This effect of postprandial triglyceridaemia on VIIc persisted after allowance for the effect of VIIag on VIIc. Dietary fat composition did not influence VIIc or VIIag. The results suggested an acute but evanescent effect of triglyceride-rich lipoproteins on the reactivity of factor VII, irrespective of their lipid core composition.

Antigens↗

Two new immunogenetic polymorphisms of the apoB gene and their effect on serum lipid levels and responses to changes in dietary fat intake.

In previous studies, apoB polymorphisms have been shown to modify serum lipid responses to changes in dietary fat intake. The functionally important apoB DNA change or changes underlying these effects have, however, remained unknown. Using a single-strand conformation polymorphism analysis-based screening method, we identified two previously unreported apoB polymorphisms located close to each other in the 5' region of apoB gene exon 26. This DNA segment corresponds to the binding site of monoclonal anti-apoB antibody D7.2. The two A-->G changes at apoB cDNA nucleotides 5869 and 5896 produced an Asn-->Ser change at amino acid 1887 and a His-->Arg change at amino acid 1896. In the Finnish population, allele frequencies of the rare alleles of the apoB 1887 (Asn-->Ser) and apoB 1896 (His-->Arg) polymorphisms were .02 and .11, respectively. Both polymorphisms were shown to have an independent effect on the binding affinity of LDL with monoclonal antibody D7.2. The effect of these polymorphisms on serum lipid levels and responses to changes in dietary fat intake in 102 healthy free-living subjects was assessed. The apoB 1896 Arg allele was associated with a higher serum LDL cholesterol level during a low-fat, low-cholesterol diet in men.

Alleles↗

Combined effects of dietary fat and birth weight on serum cholesterol concentrations: the Hertfordshire Cohort Study.

BACKGROUND: Blood cholesterol responses to the manipulation of dietary fat vary widely between persons. Although epidemiologic evidence suggests that prenatal growth and nutrition influence adult cholesterol homeostasis, whether prenatal growth modifies the association between dietary fat intake and serum cholesterol concentration in adults is unknown. OBJECTIVE: The aim was to examine the relation between fat intake and serum cholesterol concentrations in men and women whose birth weights were known. DESIGN: We studied a cohort of men and women aged 59-71 y. Diet was assessed with a food-frequency questionnaire. Total, HDL-, and LDL-cholesterol concentrations and the ratio of HDL to LDL cholesterol were measured in fasting blood samples from 574 men and 562 women who did not have coronary heart disease. RESULTS: Total and saturated fat intakes were not associated with serum cholesterol concentrations in men or women. However, subdivision by birth weight showed associations in men but not in women. High intakes of total and saturated fat were associated with reduced HDL-cholesterol concentrations in men with birth weights < or =3.2 kg (7 lb) but not in men with higher birth weights. Similar effects on the HDL-to-LDL cholesterol ratio were observed (P for interaction = 0.02 for total fat and 0.01 for saturated fat). When 32 men taking cholesterol-lowering medication were excluded, the interactions were strengthened (P = 0.008 and 0.006, respectively). CONCLUSION: The adverse effects of high intakes of total and saturated fat on serum cholesterol concentrations in men may be confined to those with lower birth weights.

Aged↗

Dietary fat, adipose tissue composition, and the development of carcinoma of the colon.

Dietary fat and plasma lipids have been implicated in the development of carcinoma of the colon. Because of the difficulties in obtaining accurate dietary histories, subcutaneous adipose tissue fatty acids were analyzed to compare fat intake in 3 groups of patients undergoing colonoscopy: patients with carcinoma of the colon (n = 53; average age, 64 yr; 47% male), patients with neoplastic polyps (n = 34; age 63 yr; 71% male), and patients with normal findings (controls; n = 68; age 58 yr; 40% male). The groups were similar with regard to body mass index and coffee and egg consumption. One-way analysis of variance of the plasma total cholesterol, triglycerides, high-density lipoprotein cholesterol, 9 adipose fatty acids, groups of polyunsaturated fatty acids (vegetable origin), saturated fatty acids (animal origin), or the ratio of polyunsaturated to saturated fatty acids did not show any significant differences across the 3 groups. The quality of dietary fat does not appear to be associated with the development of carcinoma of the colon or of neoplastic polyps in this population.

Adipose Tissue↗

Are dietary recommendations for dietary fat reduction achievable?

Despite several sets of dietary guidelines aimed at reducing fat intakes in the UK populations the actual fat intake in the UK has remained remarkably constant over the last decade. It is therefore of utmost importance to understand why the advice of the 1980s was not taken on board by the nation, to enable the achievement of current nutritional targets for dietary fat set for 2005. The nature of the diets of those individuals in the UK who have low fat intakes in line with the dietary goals are considered here, with the aim to increase our understanding of how the goals can be achieved in the free-living population. This paper postulates that a low fat diet will be easier to achieve, more palatable and hence more acceptable to the consumer if the dietary fat is replaced with a mixture of energy from sugar and starch. Further research is required to gain a greater understanding of what type of dietary composition will enable the free-living population to achieve a reduction in their dietary fat intake. This in turn will allow the dissemination of appropriate nutritional advice in the future and inform product development initiatives in the food industry.

Attitude to Health↗

Effect of dietary fats differing in degree of unsaturation on gene expression in rat adipose tissue.

To test the possibility that the type of dietary fat affects the expression of proteins involved in adipose tissue metabolism, levels of mRNA for lipoprotein lipase, leptin, glucose transporter 4, and uncoupling protein in adipose tissues were compared among rats fed a low-fat diet (2% safflower oil), and high-fat diets containing 20% saturated fat (palm oil) or unsaturated fat rich in linoleic acid (safflower oil) for 3 weeks. High-fat diets decreased the lipoprotein lipase mRNA level in epididymal but not in perirenal white adipose tissue, but increased it in brown adipose tissue. Leptin gene expression in perirenal white adipose tissue was significantly higher in rats fed high-fat diets than in those fed a low-fat diet. High-fat diets failed, however, to alter this parameter in epididymal white adipose tissue and interscapular brown adipose tissue. mRNA levels of glucose transporter 4, both in epididymal and perirenal white adipose tissues, were lower in rats fed high-fat diets than in those fed a low-fat diet. Uncoupling protein gene expression in interscapular brown adipose tissue was 2-3 times higher in rats fed high-fat diets than in those fed a low-fat diet. The abundance of mRNAs for lipoprotein lipase, leptin, glucose transporter 4 and uncoupling protein was, however, comparable between rats fed diets high in safflower and palm oil. We concluded that the high-fat diet influences gene expression of adipose tissue in a site-specific manner. The difference in the degree of unsaturation of dietary fats is rather irrelevant in modifying the level of mRNAs for proteins related to energy metabolism and expenditure in adipose tissue.

Adipose Tissue↗

Effect of dietary fat on diabetes-induced changes in liver microsomal fatty acid composition and glucose-6-phosphatase activity in rats.

Experimental diabetes may manifest itself in a defect in liver microsomal fatty acid desaturation and increased activity of glucose-6-phosphatase (G-6-Pase). The present study was designed to determine whether these changes could be normalized by a change in the dietary fat consumed. Control and streptozotocin-induced diabetic rats were fed nutritionally adequate diets which varied in fatty acid composition. Fatty acid analysis of liver microsomal phospholipids revealed that non-diabetic control animals fed saturated fat (beef tallow) or a diet high in omega 3 fatty acids (fish oil) exhibited a significantly higher level of 18:2 omega 6 and a lower level of 20:4 omega 6 in the phosphatidylcholine and phosphatidylethanolamine fractions compared with diabetic animals. Control and diabetic animals fed the high linoleic acid diet had similar levels of 18:2 omega 6 in the microsomal phosphatidylcholine and phosphatidylserine fractions. Microsomal G-6-Pase activity was higher in diabetic than in control animals. Activity of G-6-Pase was lower in microsomes of control animals fed the soybean oil or the fish oil diet, but was not significantly reduced in diabetic animals fed high polyunsaturated fats. Blood glucose levels were similar in control groups fed the different diets, but the plasma hemoglobin Alc level was lower in diabetic animals fed the soybean oil diet. Cholesterol and triglyceride levels were lower in diabetic animals fed the fish oil-based diet. The results suggest that dietary fat manipulation has the potential to change at least some of the abnormalities in the microsomal membrane in experimental diabetes.

Animals↗

Dietary fat mediates hyperglycemia and the glucogenic response to increased protein consumption in an insect, Manduca sexta L.

Many insects display non-homeostatic regulation over blood sugar level. The concentration of trehalose varies dramatically depending on physiological and nutritional state. In the absence of dietary carbohydrate, blood trehalose in larvae of the lepidopteran insect Manduca sexta is maintained by gluconeogenesis and is dependent on dietary protein consumption. In the present study, the effect of dietary fat on the glucogenic response of insects to increased dietary protein was examined by NMR analysis of (2-13C)pyruvate metabolism. Last instar larvae were maintained on a carbohydrate-free chemically defined artificial diet having variable levels of casein with and without corn oil. Gluconeogenic flux, the ratio of the rate of gluconeogenesis to the rate of glycolysis, was estimated from the 13C distribution in trehalose arising by gluconeogenesis and the 13C enrichment of alanine due to pyruvate cycling. Insects grew well on carbohydrate-free diets and growth increased with increasing dietary protein level. At all dietary protein levels, larvae grew better on diets with fat. Without dietary fat, larvae were glucogenic but displayed low blood trehalose concentrations, <30 mM, regardless of protein consumption. When fat was included in the diet, however, gluconeogenic flux and blood trehalose level increased sharply in response to increased dietary protein level, with trehalose concentrations >50 mM at higher levels of protein consumption. When offered a choice of a high carbohydrate and a high protein diet, larvae maintained on diets with fat displayed a food preference related to blood sugar level. Those with low blood sugar fed on carbohydrate, while those with high blood sugar preferred protein. Trehalose synthesized from (2-13C)pyruvate exhibited asymmetry in the 13C distribution in individual glucose molecules, indicating a disequilibrium at the triose phosphate isomerase-catalyzed step of the gluconeogenic pathway. In trehalose from larvae on diets with fat, the asymmetric 13C distribution was higher than in trehalose from insects on diets lacking fat. This may partially result from isotopic disequilibrium when unenriched glycerol is metabolized to dihydroxyacetone phosphate following fat hydrolysis. The asymmetry in 13C distribution, however, also occurred in insects on diets without fat and decreased with increased gluconeogenic flux suggesting that true disequilibrium between the triose phosphates is the principal reason for the asymmetry.

Animals↗

Dietary fat intake and risk of type 2 diabetes in women.

BACKGROUND: The long-term relations between specific types of dietary fat and risk of type 2 diabetes remain unclear. OBJECTIVE: Our objective was to examine the relations between dietary fat intakes and the risk of type 2 diabetes. DESIGN: We prospectively followed 84204 women aged 34-59 y with no diabetes, cardiovascular disease, or cancer in 1980. Detailed dietary information was assessed at baseline and updated in 1984, 1986, and 1990 by using validated questionnaires. Relative risks of type 2 diabetes were obtained from pooled logistic models adjusted for nondietary and dietary covariates. RESULTS: During 14 y of follow-up, 2507 incident cases of type 2 diabetes were documented. Total fat intake, compared with equivalent energy intake from carbohydrates, was not associated with risk of type 2 diabetes; for a 5% increase in total energy from fat, the relative risk (RR) was 0.98 (95% CI: 0.94, 1.02). Intakes of saturated or monounsaturated fatty acids were also not significantly associated with the risk of diabetes. However, for a 5% increase in energy from polyunsaturated fat, the RR was 0.63 (0.53, 0.76; P < 0.0001) and for a 2% increase in energy from trans fatty acids the RR was 1.39 (1.15, 1.67; P = 0.0006). We estimated that replacing 2% of energy from trans fatty acids isoenergetically with polyunsaturated fat would lead to a 40% lower risk (RR: 0.60; 95% CI: 0.48, 0.75). CONCLUSIONS: These data suggest that total fat and saturated and monounsaturated fatty acid intakes are not associated with risk of type 2 diabetes in women, but that trans fatty acids increase and polyunsaturated fatty acids reduce risk. Substituting nonhydrogenated polyunsaturated fatty acids for trans fatty acids would likely reduce the risk of type 2 diabetes substantially.

Adult↗

Dietary fat promotes mammary tumorigenesis in MMTV/v-Ha-ras transgenic mice.

The purpose of this study was to investigate the influence of dietary fat on mammary tumorigenesis in MMTV/v-Ha-ras transgenic mice. Female MMTV/v-Ha-ras transgenics were fed diets providing 0, 5 or 25% of calories from corn oil (CO). The mammary tumor incidence was 7% (0% CO), 36% (5% CO) and 52% (25% CO). Ras mRNA levels were increased in mammary tumors in the 25% CO group. The ras transgene was hypomethylated in mammary tumors, but not in liver or nontransformed mammary tissue. Mammary tumors expressed apolipoprotein E mRNA. Alterations in gene structure and expression in transgenic mice may suggest mechanisms by which dietary fat promotes mammary tumors.

Animals↗