Effect of dietary restriction on the age-dependent changes in the expression of antioxidant enzymes in rat liver

The effects of aging and dietary restriction on the expression of several enzymes (superoxide dismutase, catalase and glutathione peroxidase) that are involved in free radical detoxification were studied in liver tissue from male Fischer F344 rats. The expression (i.e., activities and mRNA levels) of superoxide dismutase (Cu-Zn) and catalase decreased with age in liver. Dietary restriction (40% restriction of energy intake) increased the activities of superoxide dismutase (24 to 38%) and catalase (64 to 75%) in liver at 21 and 28 mo of age. Glutathione peroxidase activity in liver of diet-restricted rats was significantly higher (37%) at 28 mo of age than that of rats fed ad libitum. The age-related changes in the relative levels of mRNA for superoxide dismutase, catalase and glutathione peroxidase paralleled the changes in the activities of these enzymes in rats fed ad libitum or rats fed the restricted diet. Thus, the changes in the activities of superoxide dismutase, catalase and glutathione peroxidase with age and dietary restriction appear to arise from changes in the levels of mRNAs coding for these enzymes. Free radical damage, as measured by thiobarbituric acid-reactive material and lipofuscin accumulation, was lower in diet-restricted rats than in rats fed ad libitum.     

Relationships among dietary protein, feed intake and changes in body and tissue composition of lactating rats

To quantify effects of protein and energy intake on changes in tissue composition in lactating rats, 36 rats were fed three diets (L, M and H, containing 12,24, and 36% protein, respectively) at four levels of intake (100, 70, 50 and 30% of ad libitum) from d 7 to 14 of lactation. Three rats per treatment were killed on d 14; carcass, viscera, liver and mammary glands were dissected and analyzed for water, fat, protein and ash. Twelve rats killed on d 7 provided initial composition estimates. All rats lost weight loss was affected slightly by diet but drastically by intake, ranging from 22.4 g in ad libitum-fed rats to 79.9 g in the 30% group. Fat losses, mostly from carcass, were insensitive to diet but were increased to maximum at the 70% intake level, and further restriction did not result in significantly greater fat losses. Protein losses in all tissues increased with degree of feed restriction. Protein losses in viscera, liver and mammary decreased with higher dietary protein. Possible homeorrhetic adaptations responsible for these patterns of nutrient partition are discussed in terms of changes in rates of fat and protein turnover and hormonal effects upon these rates.     

Relationships among dietary protein, feed intake and tissue protein turnover in lactating rats

Effects of protein and energy intake on tissue protein synthesis and degradation were studied in rats fed 12, 24 and 36% protein diets at 100, 70, 50 and 30% of ad libitum intake begining on d 7 of lactation. Rates of protein synthesis were measured in liver, mammary, abdominal viscera and remaining carcass of rats on d 10 of lactation. Tissue protein loss was estimated as the difference in tissue protein from d 7 to 14. Data were analyzed using stepwise multiple quadratic regression to define response surfaces of protein loss, synthesis and degradation to intake of protein and energy. Protein loss increased with restriction of energy and protein intake in all tissues. However, carcass protein synthesis and degradation did not vary systematically with either energy or protein intake. Energy intake restriction increased visceral protein turnover while protein intake restriction decreased rate of protein turnover. Liver protein loss increased with decreased dietary protein due to increased liver protein degradation. Decreased energy intake also increased liver protein loss without directly affecting rate of synthesis or degradation. Mammary protein synthesis decreased very slightly with energy restriction while decreased protein intake sharply inhibited protein synthesis.     

能量限制对大鼠脂联素及PPARγ基因表达的影响

目的探讨限制能量摄入对大鼠内脏脂肪中脂联素(adiponectin)和PPARγ基因表达的影响。方法选用36只雄性Wistar大鼠,按体重随机分为基础组、限能1组和限能2组,单笼喂养12w,检测大鼠在自由摄食、80%和60%限能水平下空腹血糖、血脂和血胰岛素水平的变化;取内脏脂肪组织采用RT-PCR法检测脂联素和PPARγ基因表达水平。结果限能组TG水平显著低于基础组(P<0.05),HDL-C水平显著高于基础组(P<0.05),空腹血糖水平与基础组比较差异无统计学意义,限能2组TC水平显著高于基础组(P<0.05);限能组大鼠内脏脂肪中脂联素及其PPARγ基因表达水平均显著高于基础组(P<0.05),60%限能组又显著高于80%限能组(P<0.05)。结论限制能量摄入增高脂联素及PPARγ基因表达水平且均与限能程度有关;能量限制可能通过激活PPARγ诱导脂联素基因表达。     

Effect of energy restriction on riboflavin retention in normal and deficient tissues of the rat

We investigated the effects of energy restriction on tissue riboflavin depletion and subsequent repletion of deficient tissues. Groups of male Sprague Dawley rats with average body weights between 268 and 275g were placed on energy-restricted diets consisting of 8g (31kcal or 130kJ) per day of a basal diet adequate in all other nutrients and either 12mg of riboflavin/kg or no added riboflavin. The ad libitum controls received additional energy as a mixture of sucrose, starch, and corn oil (10:3:1 by wt). No significant difference in the degree of riboflavin deficiency was detected between energy-restricted and ad libitum-fed rats as assessed by riboflavin concentrations in the liver and gastrocnemius and soleus muscles and by the erythrocyte glutathione reductase activity coefficient (EGRAC). Additional energy-restricted riboflavin-deficient rats were subsequently repleted by feeding either the supplemented basal diet with no additional energy or with ad libitum energy. Repletion of liver riboflavin concentration and reduction of the EGRAC values to control levels occurred regardless of energy intake. Muscle riboflavin concentrations were normal in the ad libitum-fed group but decreased in the energy-restricted rats despite 4 weeks of supplementation. The latter group had muscle riboflavin levels similar to those in the rats fed the riboflavin-deficient diet for 8 weeks. The results suggest that energy restriction impairs flavo-protein synthesis in muscle but not in the liver.     

Protein synthesis in mammary acini isolated from lactating rats: effect of maternal diet

Protein synthesis in the rat mammary gland has been studied using acini isolated from mammary tissue by collagenase digestion. When the acini were incubated with radioactively labeled amino acids, both cellular and milk proteins were synthesized and milk proteins were secreted into the incubation medium. Antisera to the lipogenic enzyme, fatty acid synthase, and the milk proteins, alpha-lactalbumin and the caseins, raised in rabbits, were shown to be specific by analyzing immunoprecipitates on sodium dodecyl sulfate--polyacrylamide gels. The rates of synthesis and secretion of each protein by acini prepared from rats during late gestation and at specific stages of lactation reflect their previously observed concentration in the mammary gland or milk of rats at the corresponding stage of gestation or lactation. Rats were treated according to one of the following regimes between d 7 and 14 of lactation: they were fed a control (20% casein) or a low protein (10% casein) diet ad libitum, they were fed the control diet restricted to 25 g/d (40% of the voluntary intake), they were fed the control diet for 5 d and starved for 48 h or they were treated as in 3 and then refed the control diet ad libitum for 24 h. Food restriction and starvation both resulted in lowered rates of synthesis of all proteins examined compared with either the control or refed animals. Starvation also lowered the rates of secretion of the milk proteins. Consumption of the low protein diet caused a specific decrease in both the rates of synthesis and secretion of alpha-lactalbumin compared with the control rats without affecting the synthesis and secretion of the caseins.     

Response of adult lean and obese female Zucker rats to food restriction and refeeding

Lean and obese female Zucker rats were either fed ad libitum (ad libitum-fed lean and ad libitum-fed obese), food-restricted (restricted lean and restricted obese) at 50% of ad libitum intake for 3 weeks from 19–20 weeks of age, or food-restricted and then refed ad libitum for 1 week (restricted-refed lean and restricted-refed obese). Following food restriction, body weights of restricted rats were significantly lower than ad libitum-fed rats within genotype. Body weights of restricted-refed rats were not different from either ad libitum-fed or restricted rats within genotype. Restricted-refed lean rats returned to their previous ad libitum food intake, whereas restricted-refed obese rats ate significantly more food. Both restricted and restricted-refed lean rats had lowered serum insulin levels compared to ad libitum-fed lean rats, whereas there was no effect on serum insulin levels in obese rats. Liver weights and hepatocyte conversion of glucose to fatty acids, glyceride-glycerol and CO₂ were not affected by food restriction or refeeding in lean rats. Among obese rats, restricted obese rats had the smallest liver weights, and restricted-refed obese rats had the highest. Restricted-refed obese rats had greater rates of hepatic glucose metabolism compared to all other groups. Ad libitum-fed lean and restricted-refed lean rats had similar fat pad weights that were significantly greater than those of restricted lean rats. Dietary intervention had no effect on fat pad weight in obese rats. There was no effect of food restriction or refeeding on adipocyte glucose metabolism except for higher glucose conversion to CO₂ for restricted lean rats in comparison to values for all other groups. These results demonstrate that body weight changes of adult female obese rats in response to food restriction and refeeding are similar to those of lean rats; but the effects of liver and adipose tissue weights are different.     

Nutritionally-directed compensatory growth enhances mammary development and lactation potential in rats.

A nutritionally-regulated compensatory growth regimen imposed during a growing period from prepuberty to gestation can significantly affect mammary development and subsequent lactation performance. The objectives of this study were as follows: 1) to determine whether a compensatory nutrition regimen enhances lactation potential for the first and second lactation cycles and 2) to determine the extent to which a compensatory nutrition regimen modulates cell proliferation, differentiation, and apoptosis and expression of genes in mammary tissues of female rats. Female Sprague-Dawley rats (n = 122, 35 d of age) were randomly assigned either to the control group, with free access to diet, or to a stair-step compensatory nutrition feeding regimen, with an alternating 2-2-3-3-wk schedule. The regimen began with an energy-restricted diet (40% restriction) for 2 wk, followed by the control diet for 2 wk; this step was then repeated at 3-wk intervals. Pups of dams from the compensatory nutrition regimen group gained more during mid-lactation than did control group pups. Mammary tissues were obtained from early (d 2) and late (d 19) lactating rats. Mammary tissue from the compensatory nutrition group exhibited increased cell proliferation and greater gamma-glutamyltranspeptidase and ornithine decarboxylase gene expressions than did tissue from the control group during early lactation of both cycles. Mammary tissue from the compensatory nutrition group also had fewer apoptotic cells than tissue from the control group during late lactation of the first lactation cycle. These results suggest that the compensatory nutrition regimen imposed during the peripubertal developmental phase stimulated mammary growth and enhanced lactation performance by affecting the expression of genes that regulate the cell cycle.     

Effect of liver denervation on compensatory changes in food intake, body composition and hepatic enzyme induction after food restriction in rats

The mechanisms involved in the recovery of body fat and liver metabolism after food restriction and refeeding are not understood. This study's aim was to determine the need for hepatic neural input for the compensatory changes in food intake, body composition and hepatic lipogenic enzymes seen upon realimentation after energy restriction. Rats underwent total surgical hepatic denervation or had sham operations. One group of sham-operated and denervated rats was fed a semipurified diet ad libitum; a second group was restricted to 40% ad libitum levels for 7 d, then given free access to food during a 2-d refeeding period. Body fat content and body fat recovery rate from below "set point" were not altered by hepatic denervation. These observations do not rule out liver involvement because blood-borne factors communicating energy status information to the central nervous system could be released from the liver. The activities of hepatic enzymes--glucose-6-phosphate dehydrogenase, malic enzyme and citrate cleavage enzyme--were stimulated at least twofold by restriction and refeeding when compared to ad libitum feeding. Hepatic denervation had no effect on basal enzyme levels in ad libitum-fed animals or on elevated enzyme activity induced by refeeding after food restriction. This study clearly demonstrates that hepatic innervation is not essential for energy balance and body composition regulation. The induction of lipogenic enzymes by food restriction and refeeding does not depend on central nervous system input to the liver.     

Effects of energy restriction on mouse mammary tumor virus mRNA levels in mammary glands and uterus and on uterine endometrial hyperplasia and pituitary histology in C3H/SHN F1 mice

We investigated the effects of energy restriction on the pituitary-ovarian axis and on a hormone responsive gene, the mouse mammary tumor virus (MMTV). Female C3H/SHN F1-hybrid mice, known to display a high incidence of mammary tumors, ate an energy-restricted diet (48 kcal/wk) or a control diet (95 kcal/wk) beginning at the time of weaning. By 67 wk of age, 12 of 32 mice in the control group, but none of the 33 mice in the energy-restricted group, had developed mammary tumors. Six tumor-free mice from each group were studied in detail at 67 wk of age. All six tumor-free control mice, but none of the six energy-restricted mice, showed uterine endometrial hyperplasia at autopsy. Mice subjected to energy restriction did not display an estrous cycle. The average levels of MMTV mRNA in mammary glands and uteri were strongly reduced by energy restriction. MMTV mRNA levels in mammary glands from control mice were two orders of magnitude lower than those in mammary tumors. Energy restriction lowered the percentage of pituitary mammatropes and suppressed proliferation of mammatropes with advancing age. Energy restriction thus appeared to inhibit endometrial hyperplasia and to decrease MMTV production at the mRNA level in the mammary glands and in the uterus. These effects may be a consequence of hormonal changes originating at the pituitary-ovarian axis.     

Caloric restriction modulates insulin receptor signaling in liver and skeletal muscle of rat

OBJECTIVE: We investigated how the insulin/insulin-like growth factor-1 signaling pathway is involved in the robust antiaging effects produced by caloric restriction. METHODS: We subjected male rats to feeding ad libitum or calorie restriction, i.e., 60% of the ad libitum amount, for 2 and 25 mo and then assessed the effects of calorie restriction on insulin receptor (IR) signaling in liver and skeletal muscle. RESULTS: The results indicated that aging was accompanied by a significant decrease in IR tyrosine phosphorylation after insulin stimulation in live and skeletal muscle, which was associated with a significant increase in the activity of protein tyrosine phosphatase-1B. However, these age-related alterations were attenuated by long-term calorie restriction. Expression profile of mRNA showed an increased expression of mRNAs for IR and insulin-like growth factor-1 receptor in both tissues of calorie-restricted rats, but increased expression of IR mRNA was dissociated with the IR gene product in rats maintained on long-term calorie-restricted diet. CONCLUSION: IR signaling may play an important role in aging and its retardation by calorie restriction, and normal function of IR in liver and skeletal muscle is required for healthy aging and extending lifespan in mammals.     

Effect of dietary protein and food restriction on milk production and composition, maternal tissues and enzymes in lactating rats

Lactating rats have been fed either a protein-restricted diet (10 vs. 20% casein in the control diet) or the control diet at 80, 60 and 40% of the voluntary intake for 7 d from d 7 of lactation. Food consumption, changes in maternal live weight, litter live weight gain and the mass of several maternal tissues were determined together with the activity of several mammary and liver enzymes, including 10 that are essential for fatty acid and complex lipid synthesis. Milk production was estimated from the litter weight gain and litter weight. Lactating rats fed the 20% protein diet ad libitum consumed three times that of nonlactating rats; their liver and kidney masses were significantly higher and their adipose mass was lower. The livers of the lactating rats were fatty, containing 118 mg lipid/g compared with 42 mg/g for the nonlactating rats. Lactating rats fed either the protein-restricted diet or the control diet at 40 and 60% of the ad libitum intake of the control diet had lower mammary, liver and kidney masses than rats consuming the control diet ad libitum. Both protein and food restriction led to lower rates of milk production than those of ad libitum-fed control rats as evidenced by the decrease in litter live weight gains. The concentrations of total lipid, total protein and lactose in milk were not affected by these dietary treatments. The concentration of alpha-lactalbumin in milk of rats fed the low protein diet was, however, lower than that in the milk of all rats receiving the control diet, irrespective of intake. Consumption of the restricted diets resulted in only small changes in specific activities (mu/mg protein) of 15 mammary enzymes. In the livers, lactation led to higher specific activities of all four soluble lipogenic enzymes examined but did not affect the particulate enzymes involved in complex lipid synthesis. The dietary restrictions resulted in lower specific activities of the soluble enzymes compared with those of the lactating rats consuming the control diet ad libitum without affecting the particulate enzymes. Total activities of these enzymes were, however, lower than those for the control rats as a result of the smaller liver mass in the rats receiving the restricted diets.     

Regulation of glucose-6-phosphate dehydrogenase and malic enzyme in liver and adipose tissue: effect of dietary trilinolein level in starved-refed and ad libitum-fed rats.

The responses of glucose-6-phosphate dehydrogenase (G6PD) (EC 1.1.1.49) and malic enzyme (ME) (EC 1.1.1.40) were studied in liver and adipose tissue of rats fed for 2 days a high glucose diet containing levels of synthetic trilinolein ranging from 0 to 25% (w/w) of the diet (trilinolein was substituted for glucose). One group of rats was starved for 2 days before the trilinolein-containing diets were fed (starved-refed); a second group of rats was fed a fat-free diet for 7 days before the trilinolein-containing diets were fed (ad libitum). Liver G6PD activity decreased exponentially and liver ME activity decreased linearly with increasing dietary trilinolein in starved-refed rats, but did not decrease significantly in ad libitum fed rats. Total liver lipid decreased exponentially with increasing trilinolein in starved-refed rats, but increased exponentially in ad libitum fed rats. Adipose tissue G6PD and ME activities decreased slightly with increasing trilinolein in starved-refed rats, but did not decrease in ad libitum fed rats. When the data were adjusted by analysis of covariance for differences in glucose intake, the liver responses in starved-refed rats were still significant but the adipose tissue responses were not, indicating that the responses of adipose tissue (but not of liver) may have resulted from decreased glucose intake rather than from increased trilinolein intake. The results suggest that dietary trilinolein inhibits the characteristic increase in liver G6PD, ME and total lipids upon starvation-refeeding. However, after the levels of these parameters have been increased by feeding a fat-free diet they cannot be decreased by dietary trilinolein in 2 days.     

Response of adult lean and obese female Zucker rats to intermittent food restriction/refeeding

Previously, it was found that lean and obese Zucker rats (9-15 wk of age) responded differently to the first of four cycles of food restriction/refeeding. In later cycles, they responded similarly. The present study was undertaken to determine if this finding was due to age, adaptation to the intervention or the obesity. Adult (35-wk-old) lean and obese rats were classified into four groups, ad libitum-fed lean and obese and food-restricted lean and obese. Food-restricted rats underwent four 3-wk periods when they were fed 50% of their ad libitum intake, each followed by a 3-wk period of ad libitum refeeding. Food-restricted rats lost and regained sufficient weight in each cycle to weigh a similar amount as their ad libitum-fed groups by the end of each refeeding period. In lean rats, there were no permanent effects of this intervention except for a 25% reduction in carbohydrate intake. Similar results were found in obese rats, although they did have significantly lower retroperitoneal fat pad weight and serum triacylglycerol levels than ad libitum-fed obese rats at the end of the experiment. These results indicate that lean and obese adult rats respond to each food restriction/refeeding cycle in a similar manner. Results in the earlier experiment would appear to be due both to age and genotype.     

Effect of dietary restriction on liver protein synthesis in rats

At 6 wk of age, male Fischer F344 rats were fed a purified, casein-based diet either ad libitum or in the amount of 60% of the diet consumed by the rats fed ad libitum (restricted diet). Hepatocytes were isolated from the rats between 2.5 and 19 mo of age. The protein content of the hepatocytes isolated from the rats fed the restricted amount of diet was significantly lower than that of hepatocytes isolated from rats fed ad libitum. The DNA and RNA content of the hepatocytes were similar for the rats fed the two dietary regimens. The absolute rate of protein synthesis for hepatocytes isolated from rats fed ad libitum decreased 55% between 2.5 and 19 mo of age. However, the rate of protein synthesis by hepatocytes from rats fed the restricted amount of diet decreased only slightly with increasing age. At 19 mo of age, the rate of protein synthesis by hepatocytes from the rats fed the restricted amount of diet was significantly higher than the rate of protein synthesis for hepatocytes from rats fed ad libitum. Therefore, dietary restriction retards the age-related decline in liver protein synthesis.     

Effects of dietary protein, fat and energy intake during an initiation phase study of 7,12-dimethylbenz[a]anthracene-induced breast cancer in rats

A factorial experiment was conducted to examine the effects of dietary protein (8, 16, 32% of energy from casein) and dietary fat (12, 24, 48% of energy from corn oil) on the initiation of 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast carcinogenesis in rats. Forty weanling female Sprague-Dawley rats were assigned to each of nine diets fed ad libitum. After 4 wk each rat received DMBA (20 mg/kg) via gastric intubation. For an additional 22 wk after carcinogen administration all rats consumed a diet containing 16% of dietary energy from protein and 24% from fat. Dietary fat, protein and ad libitum energy consumption exhibited statistically significant effects on final tumor prevalence, but interactive effects were not found. At necropsy, rats fed corn oil at 12, 24 and 48% of energy prior to DMBA administration showed tumor prevalences of 58, 58 and 85% with 116, 153 and 231 total tumors, respectively. The data indicate a significant nonlinear effect of dietary fat. Corresponding numbers for rats fed casein at 8, 16 and 32% of energy prior to DMBA were prevalences of 79, 65 and 59%, with total tumor counts of 194, 144 and 162. Higher dietary protein during the initiation phase was associated with a significant reduction in tumor prevalence, which was most striking between 8 and 16% of energy from protein. In addition, results of multiple logistic regression showed that tumorigenesis was increased with greater ad libitum energy intake. The odds of a tumor at necropsy were multiplied by 1.19 for each kilocalorie increase in ad libitum energy intake averaged over the post-DMBA phase of the experiment. An additional six weanling rats fed each diet for 4 wk were killed for assay of hepatic carcinogen metabolizing enzymes at the time corresponding to DMBA administration in the initiation experiment. Both protein and fat showed independent effects on the activity of several enzymes. However, enzyme activity did not suggest a unifying mechanism whereby these nutrients influence DMBA-induced mammary carcinogenesis.     

Low dosages of exogenous growth hormone and its effect on growth in an animal model of suboptimal nutrition

In a previous study, weight gain, insulin growth factor-1 (IGF-1) and insulin growth factor binding protein-3 (IGFBP-3) were increased in rats fed suboptimal levels of energy and administered 0.1 mg/100 g of body weight of recombinant human growth hormone (rhGH). Our objective was to determine whether these anabolic effects were still obtained with lower dosages of rhGH in similarly fed rats. Three groups of male, prepubertal Sprague-Dawley rats were administered rhGH and three groups of similar rats were given normal saline solution daily (0.05 mg/100 g of body weight subcutaneously). All rats were fed a balanced 1:1 carbohydrate:fat ratio diet for 4 wk. Restricted rats within each treatment were pair fed 80% and 60% ad libitum. Daily body weight, food intake, and efficiency were recorded. After 4 wk, serum IGF-1 and IGFBP-3, body fat, fat-free mass, and total body water were determined. Total weight gain and serum IGFBP-3 were significantly higher, with a tendency for increased body fat, in rats treated with rhGH and fed at 60% ad libitum. However, within each treatment, energy restriction caused decreased body fat and total body water. These results suggest that lower dosages of rhGH provide anabolic effects during suboptimal energy intake.     

Influence of selected amino acid deficiencies on somatomedin, growth and glycosaminoglycan metabolism in weanling rats

The effects of lysine-, methionine- or histidine-deficient diets compared to a control diet fed ad libitum or 15, 10 or 5 g/d were studied in weanling rats. Feed intake was 5-7 g/d for the amino acid-deficient animals. After 3 wk, all amino acid-deficient rats had lost more weight (P less than 0.01) than the controls fed at comparable energy levels. Serum somatomedin (Sm) activity was significantly decreased in lysine- (0.55 U/ml), methionine- (0.32 U/ml) and histidine-deficient (0.38 U/ml) rats compared to rats fed the control diet ad libitum (1.6 U/ml). Differences between amino acid-deficient and calorie-restricted animals were not significant. A similar response was observed in 35SO4 uptake by cartilage glycosaminoglycans (GAG). Caloric restriction and amino acid deficiency each resulted in lower 35SO4 uptake by cartilage GAG than occurred with ad libitum feeding, but there were no significant differences between the rats fed amino acid-deficient diets and those fed 5 or 10 g of the control diet. Compared to rats fed the control diet ad libitum, plasma growth hormone (GH) concentrations were lower in the rats fed 5 or 10 g of control diet per day and in those fed amino acid-deficient diets (P less than 0.05), but GH concentrations were not consistent with the growth retardation observed. The results confirm that Sm and GAG activities are reduced in protein-energy restriction independent of GH. However, changes could not be attributed to specific deficiencies of lysine, methionine and/or histidine.     

Effect of diet restriction on some key enzymes tryptophan-NAD pathway in rats.

Dietary intake of rats was restricted by feeding varying amounts of a 20% protein diet. After 6 weeks of feeding, some key enzymes of the tryptophan and nicotinic acid-NAD pathway, liver nicotinamide nucleotide concentration, and urinary metabolites of tryptophan and nicotinic acid were studied. With an increase in diet restriction, liver tryptophan oxygenase (EC 1.13.1.12) activity increased. Quinolinate phosphoribosyltransferase (EC 2.4.2.a) activity, on the other hand, was found to decrease with moderate diet restriction up to 50% restriction, but increased again with more severe diet restriction in rats fed 25% of ad libitum intake. Liver nicotinate phosphoribosyltransferase (EC 2.4.2.11) activity was also observed to decrease with moderate diet restriction and did not further change when the restriction was severe while picolinate carboxylase (EC 4.1.1.45) activity increased significantly only in severe diet restriction. In rats fed 25% of ad libitum intake, urinary quinolinic acid excretion was low whereas N'-methylnicotinamide excretion was elevated. Alterations in the enzyme activities accompanied by changes in the levels of urinary metabolites, observed in the present study, suggest that the potential efficiency of conversion of tryptophan to nicotinamide nucleotides is not constant and is influenced by dietary intake.     

Intestinal cell proliferation is influenced by intakes of protein and energy, aflatoxin, and whole-body radiation

Intestinal epithelial cell proliferation in young male F344 rats was measured in response to dietary protein content (5%, 10%, and 20% casein diets), energy restriction (energy intake was 60% of ad libitum energy intakes of animals consuming the 20% casein diet), total diet restriction (dietary intake was 60% of the ad libitum intake of 20% casein diet group), aflatoxin administration, and whole body irradiation. Cellular proliferation was measured in sections of jejunum, ileum, proximal colon, and distal colon with the [3H]thymidine technique. Restricting energy or total diet intakes by 40% from ad libitum levels reduced proliferation in epithelial cells throughout the intestine. In comparison to the 5% casein diet, the 20% casein diet resulted in modestly lower cellular proliferation in all intestinal segments. Radiation induced a decrease in cellular proliferation in the jejunum and ileum; this decrease was prevented by a 20% casein diet. Pretreatment with aflatoxin B1 decreased intestinal cell proliferation throughout the intestine, and this decrease was not influenced by the protein content of the diet.