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Effects of diet type on incidence of spontaneous and 2-acetylaminofluorene-induced liver and bladder tumors in BALB/c mice fed AIN-76A diet versus NIH-07 diet.

Diet is a major influence on the responses of experimental animals to drugs, toxins, and carcinogens. Two diets used widely in toxicological and/or nutritional studies, and considered to be nutritionally adequate, were compared with respect to their influence on growth, body weight, lifespan, spontaneous neoplasia, and neoplastic responses to 2-acetylaminofluorene (2-AAF). Both sexes of weanling BALB/c mice were fed either a purified diet (AIN-76A) or a nonpurified, natural ingredient diet (NIH-07), with or without 2-AAF for up to 2 years. Dosages of 2-AAF were administered to males at 0, 20, 40, or 60 ppm in each diet and to females at 0, 100, 125, or 150 ppm. Each group consisted of 96 mice. In most instances, males and females fed purified diet (AIN-fed) gained weight more rapidly, attained higher maximum body weights, and died earlier than their non-purified diet (NIH-fed) counterparts. 2-AAF inhibited weight gain significantly only in AIN-fed females. Thus, females receiving 150 ppm 2-AAF gained little more than their NIH-fed counterparts. At the dosages used in males, 2-AAF did not induce liver neoplasia but the AIN diet was clearly associated with a higher spontaneous frequency of liver neoplasia than the NIH diet. Although 2-AAF induced liver tumors in females fed either diet at all dosages, a higher frequency and earlier appearance of liver tumors among AIN-fed females than their NIH-fed counterparts was apparent mainly at the lowest dosage. 2-AAF induced bladder neoplasia in both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Acetylaminofluorene

The effects of continuous naltrexone infusions on diet preferences are modulated by adaptation to the diets.

Two groups of male rats were placed on a feeding regimen in which a fat/protein diet and a carbohydrate/protein diet were available ad lib. Naltrexone was infused via osmotic minipumps either at the time the diets were introduced or after one week of adaptation to the diets. In rats adapted to the diets, naltrexone caused a decrease in the intakes of fat/protein and carbohydrate/protein diets. Relative preferences for the two diets were generally unchanged. In contrast, when naltrexone was infused at the time of introduction of the diets, a polarization phenomenon was observed: rats tended to consume nearly all of their daily calories from either one diet or the other. Six rats (out of 10) showed a stronger preference for the carbohydrate/protein diet than did any of the saline-treated rats, while 3 showed a stronger preference for the fat/protein diet than did any of the saline-treated rats. Thus, the effect was not diet- or macronutrient-specific. These preferences became significantly less extreme after termination of naltrexone infusions. Conditioned aversions and naltrexone-induced reductions in exploratory behavior are discussed as potential explanations for this polarization effect. These results indicate that naltrexone has differential effects on the development versus the maintenance of diet preferences. Further, they emphasize the importance of examining individual differences as well as baseline preferences in studies on the control of intake and diet selection.

Adaptation, Psychological

Influence of quantity of diet on protein synthesis of rats force-fed a threonine-devoid diet.

The influence of the quantity of diet on protein synthesis of rats force-fed a complete diet or one free of threonine for 3 days. Protein synthesis was studied. The results revealed that rats force-fed an adequate amount (6.5 gm. per day) of threonine-devoid diet demonstrated increased hepatic and cardiac protein synthesis and decreased skeletal muscle and splenic protein synthesis in comparison to the results with rats force-fed the complete diet. In contrast, rats force-fed one-half the quantity (3.25 gm. per day) of the diets revealed no or small differences in protein synthesis of the liver, heart, gastrocnemius muscle, and spleen between the rats force-fed the complete and the threonine-devoid diets, although both of the one-half quantity groups had values which were decreased in comparison to those of rats force-fed the adequate quantity of complete diet. The tube feeding of L-threonine (60 mg.) to rats force-fed one-half the quantity of the complete or threonine-devoid diet on the 4th morning 2 hours before killing did not influence the results of organ protein synthesis. Protein synthesis was studied in vivo by measuring 14C-leucine incorporation into organ proteins and in vitro by measuring 14C-leucine incorporation into proteins by using postmitochondrial supernatants or microsomes of livers. Sucrose density gradients of hepatic polyribosomes were studied and revealed that there were more aggregated polyribosomes in rats force-fed adequate quantities of the experimental diets than in those force-fed the control diets. Rats force-fed one-half quantity of the complete and threonine-devoid diets revealed similar polyribosomal patterns which revealed more disaggregation than those in rats ofrce-fed the adequate quantity of complete diet.

Animals

Comparative effects of a recommended lipid-lowering diet vs a diet rich in monounsaturated fatty acids on serum lipid profiles in healthy young adults.

This crossover study investigated the effects of two fat-reduced diets, one rich in monounsaturated fatty acids (MUFAs), the other rich in polyunsaturated fatty acids (PUFAs), on serum lipid profiles in 38 healthy young adults initially on a typical western diet. After being randomly assigned to two groups, the subjects received the MUFA or PUFA diet for 3-wk and then the other diet for 3 wk. Both test diets led to significant reductions in serum cholesterol, LDL cholesterol, and HDL cholesterol (P less than 0.001). Both reduced apolipoprotein B (P less than 0.001) and apolipoprotein A-I concentrations (P less than 0.01 for the MUFA, P less than 0.001 for the PUFA diet). Apolipoprotein A-I was significantly higher on the MUFA than on the PUFA diet. The ratio of apolipoprotein A-I to B significantly increased on both diets. Thus, a low-fat, MUFA-rich diet is as effective as a low-fat, PUFA-rich diet in lowering total and LDL cholesterol, but both also lowered HDL cholesterol concentrations. The MUFA-rich diet may be more advantageous than the PUFA-rich one because it does not lower apolipoprotein A-I concentrations as much as the PUFA-rich diet.

Adult

The effect of a shift from a mixed diet to a lacto-vegetarian diet on human urinary and fecal mutagenic activity.

This is an investigation of the effects of a shift from a well-balanced mixed diet to a lacto-vegetarian diet on the mutagenic activity in urine and feces. The participants were 20 normal-weight, non-smoking subjects (4 men and 16 women, mean age 44 years, range 27-61 years). The fecal samples were assayed for direct-acting mutagens with the fluctuation test for weak mutagens and the urinary samples were assayed with the same assay but with a metabolic activation system, a so-called S9 fraction. The switch from a mixed diet to a lacto-vegetarian diet was not a shift from a so-called high to a low risk diet for colon cancer but rather from a 'medium high risk diet' to a 'low risk diet', even though there were significant changes in nutrients and food components between the two diets. There was a decrease in fat (P = 0.009) and protein intake (P = 0.04) and an increase in total carbohydrate (P = 0.001), fiber (P = 0.001), calcium (P = 0.006) and vitamin C intake (P = 0.019). Among the food preparation methods the use of frying decreased (P = 0.02) and the habit of eating a new vegetable meal increased (P = 0.05). Three months after the dietary shift the concentration of fecal direct-acting mutagens decreased significantly (P less than 0.05), though the total mutagenic activity excreted in feces per 24 h was not different between the two diet periods. Both the concentration and the total amount of promutagens in the urine were decreased after 3 months on the lacto-vegetarian diet. The decrease in fecal mutagenic activity might be explained by a higher fiber intake, which leads to higher water content in feces and thereby a dilution of fecal mutagenic compounds.

Adult

Effect of diet composition on metabolic adaptations to hypocaloric nutrition: comparison of high carbohydrate and high fat isocaloric diets.

The metabolic consequences of two hypocaloric diets were assessed in 10 obese men. The study, performed on a metabolic ward, compared the response of these men to two cholesterol-free liquid formula diets of differing composition (10 kcal/kg per day, 70% carbohydrate, 20% protein, 10% fat versus 70% fat, 20% protein, 10% carbohydrate) but identical in calories. These were administered for 14 days in a random order and each diet was preceded by a 7-day control weight maintenance diet (30 kcal/kg per day, 40% carbohydrate, 20% protein, 40% fat). The low calorie diets were well tolerated by the men and effected similar losses of nonaqueous body weight. Fasting glucose and insulin decreased significantly in these men after they ingested either weight loss diet for 14 days, but the change in each parameter was greater for high fat as compared to high carbohydrate (15% versus 7% and 67% versus 35%, respectively, P less than 0.01). In contrast, fasting glucagon concentration decreased in these subjects to a greater extent in response to the high carbohydrate diet (35% versus 16%, P less than 0.01). This adaptive response thus resulted in a 50% fall in insulin:glucagon molar ratio for high fat and no change for high carbohydrate weight loss. Despite these hormonal alterations no change in glucose tolerance was observed. Fasting serum triglyceride and cholesterol levels declined in these subjects to a greater extent following the high fat compared to the high carbohydrate regimen (45% versus 28%, P less than 0.01 and 8% versus 3%, not significant, respectively). These changes reflected decrements in very low density lipoproteins alone. Despite similar increments in free fatty acid levels, (350% versus 270%, not significant) serum ketone body (beta-hydroxybutyrate and acetoacetate) concentrations increased 7-fold on the high fat diet compared to the high carbohydrate diet, P less than 0.001. The hyperketonemia of these men in response to the high fat, low calorie diet suggested the occurrence of a shift in hepatic free fatty acid metabolism toward ketogenesis rather than triglyceride synthesis. The associated decrease in the insulin: glucagon molar ratio raised the question of a possible role for these hormones in the adaptation.

Adolescent

Variations in the response of the thyroid gland of the rat to different low-iodine diets: correlation with iodine content of diet.

Large variations are frequently encountered in the thyroidal responses of rats to commercially available low-iodine diets. The major aim of this investigation was to attempt to correlate these variations with differences in the iodine content of the diets. A method was developed for measuring the iodine content of low-iodine diets which was sufficiently sensitive to discriminate between a diet containing 15-20 ng of iodine per g and one containing 30-40 ng of iodine per g. Large differences were observed between various commercial low-iodine diets in their ability to induce goiter and to affect other indices of thyroid function, and these differences could be correlated with differences in the iodine content. The most severe iodine deficiency occurred in rats that were fed a Remington diet containing 15-20 ng of iodine per g. After 3 months on this diet, thyroid weight increased about 7-fold, thyroid 127I concentration was reduced to about 0.5% of control values, serum thyroxine (T4) was reduced to less than 0.25 mug/100 ml, the ratio of labeled triiodothyronine to labeled T4 was increased to 5.2, and that of labeled monoiodotyrosine to labeled diiodotyrosine was increased to 4.2. Much smaller changes were observed in the rats on the other low-iodine diets, which ranged from 30-40 to about 100 ng of iodine per g. A daily supplement of only 0.2 mug of iodide per day administered to rats on a Remington low-iodine diet produced a significant changes in thyroidal responses. These results suggest that iodine deficiency alone is sufficient to explain the effects of the Remington low-iodine diet and that it is not necessary to postulate the presence of a goitrogen.

Animals

Effect of low protein diets on free amino acids in plasma of young men: effect of wheat gluten diet.

Studies were made on alterations in plasma amino acids in young men fed a diet containing graded levels of wheat gluten. After one week on a standard diet containing 200 mgN/kg of mixed protein (animal protein content 45%), 38 young men were given a wheat gluten diet containing 170, 100, 60, 30, 15 or zero mgN/kg for 2 weeks. Blood samples measuring plasma free amino acids were taken before breakfast at the end of the periods on a standard diet and an experimental diet. In subjects on diets containing 170 to 30 mgN/kg the plasma concentrations of threonine, valine, methionine, leucine, tyrosine, phenylalanine, serine, histidine and arginine fell significantly with decrease in protein intake, but the concentration of alanine increased significantly. On the other hand, in subjects on diets containing 15 or zero mgN/kg, the plasma concentrations of the essential amino acids did not decrease, but increased to slightly more than in subjects on a diet containing 30 mgN/kg, and the alanine and glycine concentrations increased steadily. Values for plasma lysine varied from 146 +/- 22 to 194 +/- 31 mumoles/liter with gluten intakes of 170 to zero mgN/kg, but were comparable with that of 186 +/- 33 mumules/liter in subjects on a standard diet, showing that the plasma lysine concentration did not clearly reflect the dietary concentration of lysine in young men on a wheat gluten diet.

Adult

A comparison of insulin binding by liver plasma membranes of rats fed a high glucose diet or a high fat diet.

The interaction of (125)I-labeled insulin with purified liver plasma membrane from rats fed a high fat (L) diet or a high glucose (G) diet was studied with respect to specific binding, insulin degradation, binding site degradation, and rate of hormone association and dissociation. Scatchard analysis suggested the presence of high and low affinity binding sites for membranes of both G and L diet-adapted rats. However, liver plasma membrane from rats fed the high glucose diet bound 50% more insulin than did membrane from rats fed the high fat diet. Diet did not change insulin binding site degradation. The results suggested that an apparently reduced number of insulin binding sites (G = 10.2 +/- 2.45 x 10(-12) mol/mg membrane protein, L = 4.5 +/- 1.73 x 10(-12) mol/mg membrane protein) associated with fat feeding as compared to glucose feeding was responsible for the reduced insulin binding by membrane from rats fed the high fat diet. The effects of concanavalin A (Con A) on insulin binding to liver plasma membranes were also investigated. Con A enhanced the specific binding of insulin to liver plasma membranes from rats fed either diet at concentrations lower than 50 micro g/ml, whereas at concentrations higher than 50 micro g/ml Con A inhibited insulin binding to these membranes. The stimulatory effect of Con A on insulin binding at low concentrations was greater and inhibition of binding at high concentration was less in the case of membrane prepared from L diet-adapted animals. These results suggested that diet can modify the plasma membrane glycoproteins.

Animals

Influence of meal frequency on diurnal lipid, glucose and insulin levels in normal subjects on a high fat diet; comparison with data obtained on a high carbohydrate diet.

Diurnal levels of serum triglyceride (TG) were measured in six normal persons consuming a fixed solid 65% fat diet under steady state conditions in a metabolic unit. The food was divided into either three or eight similar portions, differently spaced over the day and night. The diurnal TG-profiles on this diet were practically identical to those found under comparable conditions on a 65% carbohydrate diet [1]. Mean diurnal TG values did not significantly differ with varying meal frequency. Free fatty acid levels, however, were significantly higher on a high fat diet. Post-prandial glucose and insulin reponses did not significantly differ whether a high fat diet or a high carbohydrate diet was consumed. We conclude that the composition of the diet is of little importance in determining diurnal TG patterns when the diet consists of normal food stuffs, but that these patterns are dependent on meal frequency and distribution.

Blood Glucose

Serum concentrations of insulin-like growth factor-I and proteoglycan synthesis rates in young rats: a comparative study between the regional diet of São Paulo state and casein diets.

Insulin-like growth factor-I (IGF-I), also known as somatomedin-C, is an important mediator of growth regulation. Serum concentrations of IGF-I and proteoglycan synthesis rates in the tibial epiphysis, an estimate of the biological response to IGF-I in a target tissue, were compared in weanling Wistar rats fed ad libitum (group 1) and with 50% restriction (group 2) with the regional diet of São Paulo State (RDSPS--a mean diet consumed by low-income families with rice, beans, sugar, meat, milk, fruits and other vegetables) and in pair-fed animals fed with casein diets (groups 3 and 4). Data are reported as mean +/- SD for 8 rats in each group. Proteoglycan synthesis rates (cpm/mg) were significantly higher in rats fed with the RDSPS-based diet (groups 1 and 2: 210.8 +/- 58.8, 136.6 +/- 17.6) than in pair-fed animals fed with an 11% casein diet (groups 3 and 4: 62.9 +/- 11.6, 37.7 +/- 13.7) and in control animals fed ad libitum with a 20% casein diet (group 5: 58.1 +/- 22.7). Furthermore, these rates were higher in animals fed ad libitum than in those fed with the same diets but with 50% restriction. However, similar differences between groups 1 to 4 were not observed in serum concentrations (ng/100 microliters) of IGF-I (group 1: 44.1 +/- 7.1; group 2: 40.8 +/- 3.8; group 3: 46.0 +/- 3.6; group 4: 41.6 +/- 3.4, and group 5: 63.2 +/- 7.8). These results suggest that serum IGF-I levels are not reliable indicators of IGF-I status in this experimental model.

Aging

[Behavior of certain parameters of lipid and energy metabolism. 5. Effects of high-fat and low-fat diets on certain biochemical parameters in rat livers before and after change of diet].

Typical metabolic patterns are detectable in the livers of growing rats after feeding diets with high (25%) or low (2%) fat contents. In view of the elucidation of problems related to the regulation of the metabolic processes, it is of interest to know in what way these metabolic patterns change after short-time change from the one diet to the other and if there are hierarchies. Within 2 days after change of diet, the enzymes glucose-6-phosphate dehydrogenase, NAD-malate dehydrogenase, lactate dehydrogenase, citrate synthase and fatty acid synthase were affected, only the 3'.5'-c AMP-splitting phosphodieterase showed no change. The metabolites lactate and pyruvate also changed, inversely to lactate dehydrogenase activity, the lactate-pyruvate ratio remaining almost constant. Acetyl CoA also responded in a characteristic manner. The single parameters were differently affected by the kind of the change of diet (from high-fat to low-fat diet or inversely). For example, glucose-6-phosphate dehydrogenase responded very rapidly to the change from the high-fat to the low-fat diet, malate dehydrogenase behaved inversely, and citrate synthase responded to both changes. Consequently, the regulatory processes after change of diet start from different sides. It is thinkable that this behaviour is related to the different roles of the determined parameters in fat and energy metabolism.

3',5'-Cyclic-AMP Phosphodiesterases

Glucose tolerance factor potentiation of insulin action in adipocytes from rats raised on a torula yeast diet cannot be attributed to a deficiency of chromium or glucose tolerance factor activity in the diet.

The nature of the dietary component responsible for adipocytes having the ability to respond to Glucose Tolerance Factor (GTF) was investigated. Rats were raised on either a control diet or one of three diets differing only in the protein source (torula yeast, brewer's yeast, or casein). Only in adipocytes from rats fed the torula yeast diet did a GTF fraction prepared from brewer's yeast potentiate the action of suboptimal concentrations of insulin in the incorporation of label from D-[1-14C]-glucose and D-[U-14C]-glucose into CO2 and fatty acids. It was concluded that this potentiation was not the result of a deficiency of GTF activity in torula yeast, because a GTF fraction prepared from torula yeast had similar insulin potentiating activity. Differences in response among diets were not owing to differences in levels of amino acids or owing to concentrations of 22 (Al, As, B, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mo, Na, Ni, P, Pb S, Se, Si, Sn, Sr, Zn) of the 23 trace elements investigated. The level of Mn was low in all diets, but particularly low in the torula yeast diet. Mn deficiencies have previously been implicated in perturbations of glucose metabolism, so that it is possible that this deficiency may be responsible for the effects attributed to the torula yeast diet.

Adipose Tissue

Comparative effects of a protein deprived diet on the weight, lymphocyte content and the number of DNA-synthesizing and dividing cells in the lymphoid organs of the rat. Influence of the diet on the stimulating action of phytohemagglutinin and the inhibitory action of cortisone.

The changes induced in adult male rats by a protein deprived (PD) diet lasting 7 weeks were investigated from the viewpoint of the cell contents of the popliteal lymph nodes (PLN), spleen and thymus; the levels of DNA-synthesizing lymphocytes counted on cell smear autoradiographs, and the levels of mitoses. The stimulating effect of a subplantar injection of phytohemagglutinin (PHA) and the inhibitory action of cortisone (3 mg/100 g per day for 5 days) were also determined in normal and PD rats. The PD diet significantly reduced the cell contents, primarily in the thymus, as well as the number of labeled cells and mitoses per mg of tissue and per entire organ. When expressed on the basis of 10(3) cells, the levels of both cell groups were also reduced in the spleen but not in the PLN's where they were already very low with a balanced diet. In the thymus, the sharp drop in the mitotic index (M.I.) contrasted with unchanged levels of labeled cells and an important increase in the labeling density per cell. PHA increased the M.I. to a great extent in the PLN's and spleen in normal rats but not in PD rats. In contrast, the labeling index (p. 10(3) cells) in the spleen, as well as the number of labeled cells per mg and per organ, increased in PLN's and the spleen after PHA to a much greater extent with a PD diet than with a normal diet. These results suggest a premitotic block of the cell cycle after protein deprivation. Also, the mitotic index appears to be a more reliable test, than the labeling index, of the lymphostimulating action of PHA and of its inhibition following protein removal from the diet. The effects of cortisone in normal rats resembled to a large degree those of a protein-free diet. If the hormone was administered to PD rats, the residual lymphocytes of the atrophic thymus were still more cortisone-sensitive than those of normal rats. On the contrary, DNA synthesizing cells in the PLN's and spleen, and mitoses in the spleen resisted cortisone in PD rats, while they were partly destroyed by the hormone in the controls. This suggests that primarily the cortisone-resistant lymphocytes of these organs are capable of synthesizing DNA after prolonged protein deprivation. The results are in agreement with the hypothesis of an intervention of endogenous glucocorticoid hormones in the protein lack-induced lymphoid involution.

Animals

Diet-induced atherosclerosis and experimental hypertension in stumptail macaques (Macaca arctoides). Effects of antihypertensive drugs and a non-atherogenic diet in the evolution of lesions.

This study was carried out to determine the evolution of atherosclerotic lesions during a therapeutic period during which regression might be appreciated. We produced aortic and coronary atherosclerosis in 27 young adult stumptail macaques (Macaca arctoides) by feeding a diet supplemented with 2% cholesterol and 25% fat. Hypertension was produced by bilateral or unilateral narrowing of the renal artery. After six months of this regimen, four monkeys were killed (group 1) and 23 monkeys were divided into three groups: group 2 received unsupplemented diet; group 3 received the same diet as group 2 and drug treatment for hypertension; group 4 was continued on the atherogenic diet and received antihypertensive drug treatment. The results indicate that deleting the atherogenic diet leads to a decrease in the lipid content of the lesions and a transformation of the lipid laden atherosclerotic plaques into lipid-poor, fibro-collagenous lesions, with a decrease in the amount of coronary luminal narrowing. Partial control of systolic hypertension by antihypertensive drugs did not accelerate the involution of the atherosclerotic lesions over the relatively short period of this study. No statistically significant correlation by regression analysis was observed between the level of blood pressure elevation, the plasma renin activity, or the degree of the drug response, and the severity and extent of the atherosclerotic lesions. Furthermore, severe arterial hypertension without an atherogenic diet (group 5) produced arteriosclerosis of the aorta, and intensified branch cushions in the coronary arteries, without inducing lipid deposition in either vascular bed.

Animals