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Olestra ingestion and dietary fat absorption in humans.

The effect of olestra, a zero-calorie fat replacement, on the absorption of dietary fat was determined with a dual-isotope technique in 67 healthy male subjects. After a 30-d adaptation period in which they consumed potato chips which delivered either 10 g/d olestra or 10 g/d triglyceride under free-living conditions, the subjects were housed in a metabolic ward and given 0, 8, 20 or 32 g olestra in potato chips. The chips were eaten as part of a breakfast containing about 38 g of fat, about 0.16 mg of 14C-triolein, and a nonabsorbable marker, 51CrCl3. Feces were collected for 7 d, and aliquots of the two daily collections containing the highest levels of 51Cr were oxidized. The CO2 was collected, and 14C content was determined by liquid scintillation spectrometry. The fractional absorption of 14C-triolein was calculated from the average ratios of 14C/51Cr dosed and measured in the feces. Olestra had a slight but significant dose-response effect on triglyceride absorption: the highest olestra dose (32 g) reduced absorption by 1.2%. This effect is not nutritionally significant with respect to either availability of essential fatty acids or energy intake.

Adult↗

Effect of dietary fat on the initiation of hepatocarcinogenesis by diethylnitrosamine or 2-acetylaminofluorene in rats.

The purpose of this study was to determine if increasing dietary fat, either as saturated fat or polyunsaturated fat, would alter initiation of hepatocarcinogenesis by diethylnitrosamine (DEN) or 2-acetylaminofluorene (AAF). Rats were fed one of three purified diets: a low-fat (LF) diet (containing 5% of calories as safflower oil), a high saturated fat (HSF) diet (containing 48% of calories as palm oil) and a high polyunsaturated fat (HPUF) diet (containing 48% of calories as safflower oil). Four weeks later, all rats were subjected to partial hepatectomy (PH). Rats were then divided into four groups and received no carcinogen, DEN (10 mg/kg, p.o., 24 h after PH) or AAF (25 or 100 mg/kg, p.o., 12 h after PH). Five days later, all rats were fed an unrefined diet, and 9 weeks later, all rats were fed phenobarbital in the diet for 26 weeks as a tumor promoter. In rats initiated with DEN, the number of gamma-glutamyl transpeptidase-positive and ATPase-negative foci was higher in the rats fed the HPUF diet, but not the HSF diet, as compared to rats fed the LF diet. The incidence of neoplastic nodules, the mean focal volume and the volume fraction, however, were not significantly altered by dietary fat in DEN-injected rats. The dietary fat content of the diet did not affect the induction of altered hepatic foci or neoplastic nodules in rats initiated with AAF or receiving no initiation. This study shows that initiation of hepatocarcinogenesis can be influenced by dietary fat, but that the effect may be carcinogen-specific.

2-Acetylaminofluorene↗

Dietary fat content alters insulin-mediated glucose metabolism in healthy men.

BACKGROUND: A high dietary fat intake is involved in the pathogenesis of insulin resistance. OBJECTIVE: The aim was to compare the effect of different amounts of dietary fat on hepatic and peripheral insulin sensitivity. DESIGN: Six healthy men were studied on 3 occasions after consuming for 11 d diets with identical energy and protein contents but different percentages of energy as fat and carbohydrate as follows: 0% and 85% [low-fat, high-carbohydrate (LFHC) diet], 41% and 44% [intermediate-fat, intermediate-carbohydrate (IFIC) diet], and 83% and 2% [high-fat, low-carbohydrate (HFLC) diet]. Insulin sensitivity was quantified by using a hyperinsulinemic euglycemic clamp (plasma insulin concentration: approximately 190 pmol/L). RESULTS: During hyperinsulinemia, endogenous glucose production was higher after the HFLC diet (2.5 +/- 0.3 micromol x kg(-1) x min(-1); P < 0.05) than after the IFIC and LFHC diets (1.7 +/- 0.3 and 1.2 +/- 0.4 micromol x kg(-1) x min(-1), respectively). The ratio of dietary fat to carbohydrate had no unequivocal effects on insulin-stimulated glucose uptake. In contrast, insulin-stimulated, nonoxidative glucose disposal tended to increase in relation to an increase in the ratio of fat to carbohydrate, from 14.8 +/- 5.1 to 20.6 +/- 1.9 to 26.2 +/- 2.9 micromol x kg(-1) x min(-1) (P < 0.074 between the 3 diets). Insulin-stimulated glucose oxidation was significantly lower after the HFLC diet than after the IFIC and LFHC diets: 1.7 +/- 0.8 compared with 13.4 +/- 2.1 and 19.0 +/- 2.1 micromol x kg(-1) x min(-1), respectively (P < 0.05). During the clamp study, plasma fatty acid concentrations were higher after the HFLC diet than after the IFIC and LFHC diets: 0.22 +/- 0.02 compared with 0.07 +/- 0.01 and 0.05 +/- 0.01 mmol/L, respectively (P < 0.05). CONCLUSION: A high-fat, low-carbohydrate intake reduces the ability of insulin to suppress endogenous glucose production and alters the relation between oxidative and nonoxidative glucose disposal in a way that favors storage of glucose.

Adult↗

Potentiation of triamcinolone-induced cleft palate in mice by maternal high dietary fat.

This study investigated whether the current range in dietary fat levels, which has arisen partly in response to some major health concerns, would affect frequency of congenital anomalies if continued into the period of early pregnancy. The effect of 5.6%, or 48% of calories from fat in the maternal diet, was tested on pregnant strain CD-1 mice injected with triamcinolone in doses of 0.01 mg, 0.02 mg, 0.04 mg, or 0.06 mg per day on days 11 through 14 of gestation. Frequency of cleft palate increased with increasing doses of triamcinolone, with clefts of the palate being rare at the two lower doses. No clefts appeared without triamcinolone on either diet. In combination with triamcinolone treatment, 226 fetuses exposed to a maternal low fat diet had normal palates and 86 had cleft palates. With exposure to high fat, 186 fetuses had normal palates and 101 had cleft palates, which was a significant increase in clefting (p < 0.05). Also, the latter group showed a greater degree of retardation in palate development (p < 0.05). Thus both a greater frequency and a more severe form of clefting support the conclusion that high dietary fat potentiated the cleft palate-producing effects of triamcinolone in mice.

Animals↗

Influence of supplemental dietary fat on the relative proportions of three classes of lipid in the epiphyseal cartilage of dwarf and non-dwarf chicks.

One hundred and forty-four day-old chicks were allotted to six groups in a 2 x 3 factorial design involving two strains (dwarf, dw and non-dwarf, Dw+) and three levels of supplemental dietary fat (none, moderate and high). The birds were killed at four weeks of age. The overall weight gain and the total lipid content, amount of neutral lipids, glycolipids and phospholipids in the epiphyseal cartilage of the tibia were examined. Supplemental dietary fat resulted in improved weight gain, with the non-dwarfs showing a greater increase. There was no change in total lipid in epiphyseal cartilage with different levels of dietary fat. Increase in dietary fat elicited, in both strains of birds, an increase in the proportion of glycolipids and a concomitant decrease in the proportion of neutral lipids and no change in that of phospholipids. That the stimulatory effect of dietary fat on growth was exerted through an increase in glycolipids at the site of calcification is suggested.

Animals↗

Dietary fats and arterial thrombosis: effects and mechanism of action.

Dietary fats have a pronounced effect on arterial thrombosis: in rats, long-chain saturated fatty acids are thrombogenic, oleic acid is neutral, and linoleic acid is anti-thrombotic. These effects are likely to be mediated, at least in part, by changes in platelet fatty acid composition and--consequently--platelet function. Blood coagulability and differences in vitamin E intake seem of no (or minor) importance. In man, dietary linoleic acid inhibits platelet aggregation and other parameters of platelet activation. Dietary fat effects on vascular prostacyclin formation have not yet been found.

Animals↗

Trafficking of dietary fat in obesity-prone and obesity-resistant rats.

The trafficking of dietary fat was assessed in obesity-prone (OP) and obesity-resistant (OR) male and female rats. Test meals containing [1-(14)C]palmitate were delivered through gastric feeding tubes while rats consumed a high-carbohydrate diet (HCD) or after 5 days of a high-fat diet (HFD). Over the subsequent 24 h, the appearance of (14)C was followed in the GI tract, skeletal muscles (SM), liver, adipose tissues (AT), and expired CO(2). There was no difference in the production of (14)CO(2) between OP and OR rats consuming a HCD. However, after 5 days on HFD, OR rats produced significantly more (14)CO(2) after the test meal than OP rats (P < 0.001 females, P = 0.03 males). The differential oxidation of dietary fat between OP and OR rats on HFD was not due to differences in absorption but rather was associated with preferential disposition of tracer to AT in OP rats. Measurements of lipoprotein lipase in part explained increased tracer uptake by AT in OP rats but were not consistent with increased SM tracer uptake in OR rats. Surprisingly, female rats oxidized more tracer than male rats irrespective of phenotype or diet. These results are consistent with the notion that differences in the partitioning of dietary fat between storage in AT and oxidation in SM and liver that develop shortly after the introduction of a HFD may in part underlie the differential tendency for OR and OP rats to gain weight on this diet.

Adipose Tissue↗

Chronic food restriction and reduced dietary fat: risk factors for bouts of overeating.

The purpose of this study was to determine the effect of chronic food restriction and reduced dietary fat on feeding behavior and body weight. Young female rats were fed ad lib or food restricted on a low-fat (LF) or a fat-free (FF) diet for 4 weeks. Rats then received 24-h free access to 2 diets, the maintenance diet (LF or FF) plus a novel high-fat (HF) diet (24-h intake test). After the test, all the rats were allowed chronic free access to the HF diet until body weight was stable. During the 24-h test, the restricted groups ate significantly more calories than the ad lib groups, and the FF-restricted rats ate significantly more total food, carbohydrate and protein than the LF-restricted rats; there were no differences between the two ad lib groups. During chronic free access to the HF diet, the formerly restricted rats achieved and defended lower body weights than the formerly non-restricted rats. Throughout the experiment, the ad lib groups had more body fat than the restricted groups independent of the dietary subgroup. Hence, a history of chronic food restriction predisposes to consuming more food in acute feeding situations, particularly when dietary fat is reduced, and lowers the level of body weight maintained and defended. Chronic food restriction accompanied by reduced dietary fat may increase risk for bouts of overeating.

Animals↗

Dietary fat saturation and chain length modulate guinea pig hepatic cholesterol metabolism.

The effects of dietary fat saturation and saturated fatty acid composition on plasma lipoprotein concentrations and hepatic cholesterol metabolism were investigated in guinea pigs. Animals were fed semipurified diets containing 15 g fat/100 g diet, as palm kernel, palm oil, beef tallow, lard, olive oil or corn oil. Plasma lipoprotein concentrations were significantly altered by the type of dietary fat. The LDL cholesterol concentration was highest in animals fed the diet with palm kernel and lowest in animals fed the diet with corn oil, whereas HDL cholesterol was lowest in beef tallow-fed guinea pigs (P < 0.01). Hepatic cholesteryl ester concentrations were 100% higher in animals fed diets containing polyunsaturated corn oil and monounsaturated olive oil compared with animals fed any of the saturated fat diets (P < 0.01). Hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity varied in the different dietary fat groups independent of hepatic cholesterol pools or plasma LDL concentrations. In contrast, hepatic acyl-CoA: cholesterol acyltransferase (ACAT) activity was significantly correlated with plasma LDL cholesterol across all dietary groups (r = 0.63, P < 0.001). These data demonstrate that regulation of hepatic HMG-CoA reductase activity is relatively independent of changes in plasma lipoprotein levels, whereas hepatic ACAT activity exhibits a positive correlation with plasma LDL cholesterol concentrations.

Animal Nutritional Physiological Phenomena↗

Effect of dietary fat composition on biliary cholesterol saturation index in dogs.

In dogs, the effect of dietary fat on bile cholesterol saturation index and the evolution of molar percentages of biliary lipids have been studied in both fasting and postprandial periods after a long-term adaptation period to diets which only differ in their lipidic source (olive oil and sunflower oil). It has been observed that for similar bile cholesterol saturation indexes in both groups, dietary fat altered differently biliary lipid composition through a double mechanism which involved bile acids and phospholipids. Dietary fat is postulated to affect differently the lipidic composition of bile as well as the biliary tree motility both during interdigestive and postprandial periods.

Adaptation, Physiological↗

Mechanisms by which dietary fat may stimulate mammary carcinogenesis in experimental animals.

Evidence drawn from epidemiological and experimental studies suggests that dietary fat is an important determinant of breast cancer risk and, in addition, that dietary fat acts as a modulator rather than an initiator of breast carcinogenesis. At present, however, it is not known how dietary fat exerts its tumor-promoting effects. A variety of mechanisms, some involving direct action by fat at the target organ and others involving host-mediated responses, have been proposed. The present status of one of these, namely, a mechanism based on mediation by the endocrine system, and the hormone prolactin in particular, is described. Further studies in laboratory animals are required to determine the precise cellular and molecular events which underlie the fat effect.

Animals↗

Erythrocyte membrane phospholipid composition as a biomarker of dietary fat.

BACKGROUND/AIMS: In a cross-sectional study, we investigated the relationship between erythrocyte membrane phospholipid fatty acid composition and dietary fat; we also investigated roles of menopausal status, age, body mass index (BMI) and waist-to-hip ratio (WHR) in interindividual variation of the biomarker. METHODS: Study participants were 204 women, aged 39-65 years, drawn from the ORDET cohort and selected as controls in a study of breast cancer. Membrane composition was assessed using capillary gas chromatography. Dietary fat composition was evaluated using a food frequency questionnaire. RESULTS: In pre- and postmenopausal women, erythrocyte membrane phospholipid levels of linoleic acid, oleic acid, and mono-unsaturated fatty acids were significantly associated with corresponding dietary measures (partial correlation coefficients: 0.23 and 0.39; 0.45 and 0.47; 0.40 and 0.48; respectively, in pre- and postmenopausal women). Among postmenopausal women, membrane poly-unsaturated fatty acids were correlated with the corresponding dietary measure (r=0.39, p<0.001). Membrane eicosapentanoic and docosahexanoic acid levels were significantly correlated with intake of fish/shell fish : r=0.21 and r=0.43 (premenopausal), and r=0.41 and r=0.44 (postmenopausal). Age, BMI and WHR had independent effects on membrane lipid composition. Age was associated with delta-6 desaturase activity in postmenopausal women (r=0.25, p<0.05). BMI was negatively associated with delta-9 desaturase activity in both pre- and postmenopausal women (r=-0.29, p=0.01 and r=-0.22, p<0.01, respectively). WHR was negatively associated with delta-5 desaturase activity in pre-menopausal women (r=-024, p<0.05). CONCLUSIONS: Erythrocyte membrane levels of some specific fatty acids can be used as biomarkers of these fatty acids as proportions of dietary fat.

Adult↗

Dietary fat and risk of chronic disease: mechanistic insights from experimental studies.

The primary nutritionally linked diseases are coronary heart disease, stroke and cancers of the stomach, colon, pancreas, prostate, breast, ovary, and endometrium. Dietary fats operate through a promoting mechanism. An S-shaped dose-response curve with a threshold has been demonstrated in models of breast and colon cancer in which the standard Western fat intake of 40% of energy yields a high level of promotion, and reduction of fat to 10% to 20% of energy (the traditional Japanese fat intake) has a low promoting action. In models of breast and colon cancer, saturated fats such as beef fat or lard, and monounsaturated oils, such as olive oil, display only a weak promoting effect, with the incidence of induced tumors being similar at intake levels of 40% and 10% of energy. On the other hand, the n-6-polyunsaturated oils display a strong promoting effect. Such findings may have a parallel in the low but definitely increasing slope of postmenopausal breast cancer incidence in the past 30 years as the American public decreased saturated fat intake to avoid heart disease and increased use of the n-6-polyunsaturated oils. Mechanisms underlying the cancer-promoting effect in the colon stem from increased hepatic production of bile acids, which are transferred to the intestinal tract via the bile. Ingestion of 40% fat calories yields higher concentrations of bile acids in the colon than lower levels of dietary fat ingestion. Cancer in the mammary gland is promoted through higher concentrations of fats and phospholipids in the gland as well as increased levels of estrogen secondary to production by the ovary and other endocrine tissues that, in turn, affect the generation of pituitary hormones such as prolactin and growth hormone. The n-3-fats, as found in fish and fish oils, have a pronounced inhibitory effect in models of colon and breast cancer, presumably through their shifting of prostaglandin metabolism to the generation of prostaglandins, which lower cell proliferation potential and, thus, decrease promotional effects. The role of dietary fat as a promoter can be modified by other nutritional components. Finally, one of the best pieces of evidence for an enhancing effect of many dietary fats in the nutritionally linked cancers is the current increase in the incidence of these diseases in Japan as the nutritional habits of people in that country become more Westernized.

Animals↗

Dietary fat intake and risk of epithelial ovarian cancer.

BACKGROUND: Evidence exists that dietary fat may be a contributory factor in the development of hormone-related cancers such as ovarian cancer. Previous studies have demonstrated significantly higher circulating-estrogen levels among nonvegetarian women than among vegetarian women; the increase correlated directly with consumption of saturated fat. However, the contribution that dietary fat plays in the development of hormone-related cancers remains unresolved. PURPOSE: Our purpose was to evaluate whether saturated fat intake increases the risk of ovarian cancer development. METHODS: Population-based sampling was used to acquire cases and controls over a 3-year period from the study area, which included the highly populated region surrounding the western end of Lake Ontario, Canada. From the Ontario Cancer Registry, all histologically confirmed, primary malignant or borderline malignant epithelial ovarian tumors first diagnosed from November 1989 through October 1992 among study-area residents aged 35-79 years were determined. In total, 631 eligible case subjects were identified, of whom 450 (71.3%) were interviewed concerning reproduction and diet; 564 randomly selected population control subjects were similarly interviewed. From the quantitative diet-history information, average daily intakes of macronutrients and micronutrients were calculated. Unconditional continuous logistic regression methods were used for analysis, with adjustment for age at interview, number of full-term pregnancies, years of oral contraceptive use, and total daily caloric intake. RESULTS: Saturated fat consumption was associated with increasing risk of ovarian cancer (odds ratio [OR] = 1.20 for each 10 g/day of intake; 95% confidence interval [CI] = 1.03-1.40; one-sided P = .0082). No relationship was seen with intake of unsaturated fats. Egg consumption also appeared related to increased risk (OR = 1.42 for each 100 mg of egg cholesterol per day; 95% CI = 1.18-1.72; two-sided P = .0002), though this association may have resulted from disease-related changes in the dietary practices of case subjects prior to diagnosis. Consumption of vegetable fiber (but not fruit or cereal fiber) was associated with decreased risk (OR = 0.63 for each 10 g/day; 95% CI = 0.49-0.80; two-sided P = .0001). All three nutrients (saturated fat, egg cholesterol, and vegetable fiber) remained statistically significant when included in the same regression model. CONCLUSION: Diet may contribute to risk of ovarian cancer development. IMPLICATION: If confirmed in further studies, this association may allow women to appreciably lower their risk of ovarian cancer through dietary modifications: reducing the intake of saturated fats and eating more vegetables.

Adult↗

Dietary fat reduction behaviors in college students: relationship to dieting status, gender and key psychosocial variables.

The primary objectives were to assess dietary fat reduction/avoidance behaviors within a sample of college students, and to assess the strength of the relationship between self reported fat avoidance and a number of variables including body mass index (BMI), self-esteem, and responses to the Eating Disorder Inventory (EDI) and Eating Attitudes Test (EAT). A total of 210 female and 114 male undergraduate students were administered a food habits questionnaire (which assessed four dietary fat reduction behaviors), the EDI, the dieting subscale of the EAT, and the Coopersmith Self-Esteem Inventory. Measured heights and weights were used to compute BMI. Thirty-eight percent of the females and 13% of the males reported that they had dieted with the express purpose of losing weight in the past 12 months. The finding that females in general and female dieters in particular, scored higher on the EAT dieting subscale, and relied on three of the four dietary fat reduction behaviors to a greater extent than did males, supports the assertion that women rely heavily on dietary fat avoidance as a method to reduce caloric intakes. In females, the finding that a greater degree of fat avoidance was associated with significantly lower levels of self-esteem and higher scores on the EAT and on six of the eight EDI subscales suggested that fat avoidance may be a predictor of eating pathology and/or psychosocial problems in college-aged women.

Adolescent↗

The effect of accuracy of perceptions of dietary-fat intake on perceived risk and intentions to change.

Consumption of excess fat increases risk for many health problems and diseases. In the present study, 188 undergraduate students were studied to understand self-perceptions of dietary-fat intake and the impact of those perceptions. Findings indicated that the majority of participants had inaccurate perceptions about the amount of fat in their diets. Further, compared to people who overestimated dietary-fat intake, people who underestimated fat intake had lower perceived risk of cancer, had lower intentions to change, and demonstrated less knowledge about the dietary-fat content of many foods. Findings suggest that this unrealistic underestimation of fat intake is a cognitive barrier to dietary change and people who underestimate dietary fat intake may require more intensive intervention to change their diets.

Adolescent↗