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Comparison of crowding and food restriction effects on growth, body weight gain and endocrine status in the rat.

The present work compares the effects of post-weaning crowding and those of food restriction on growth, body weight gain and the levels of several hormones, in male Sprague-Dawley rats. Crowding resulted in reduced food intake and diminished body weight gain. Rats daily receiving the same amount of food as that eaten by crowded rats (food-restricted group) showed similar body weight gain as crowded rats, but higher growth rate. Neither crowding nor food restriction altered the pituitary-adrenal axis. In contrast, both treatments decreased serum insulin, growth hormone (GH), somatomedin C (Sm-C) and thyroid-stimulating hormone (TSH) as compared to control rats. The reduction of GH and Sm-C levels was similar in crowded and food-restricted rats but that of TSH was higher in food-restricted, rather than in crowded rats. The present data indicate that the effects of crowding could only be partially explained by the concomittant reduction of food intake and that the serum levels of the hormones studied could not explain the differences between the crowded and food-restricted rats with regard to growth.

Animals↗

Dietary protein restriction during lactation in primiparous sows with different live weights at farrowing: I. Consequences on sow metabolic status and litter growth.

The hypothesis that the restriction of dietary protein during lactation has different impacts on sow metabolic status and milk production according to body weight was evaluated. From 5-months of age until farrowing, the gilts were fed to achieve body weights of 180 or 240 kg at farrowing. At this time, 38 sows were assigned to one of three groups: " 180 kg" sows not restricted in dietary protein during lactation (180CP); "180 kg" restricted in protein (180LP), or "240 kg" sows restricted in protein (240LP). Catheters were fitted in the jugular vein of 24 sows and serial blood samples were collected 1 d before and 1 d after weaning. Amongst the protein-restricted animals, heavy sows (240LP) had a smaller appetite than light sows in early lactation, resulting in lower energy and protein intakes in the 240LP than in the 180LP sows. Body protein losses were 8, 11 and 13.5% of calculated body protein mass at farrowing in the 180CP, 180LP and 240LP sows, respectively. At the end of lactation, IGF-I concentrations were lower in the 180LP than in the sows from the other groups, probably because of the uncoupling between GH and IGF-I secretions. Low IGF-I concentrations likely promote lean tissue mobilization. Glucose and insulin profiles suggested an insulin resistance state in the 240LP sows compared with the 180LP sows, which may explain, at least in part, the lower feed intake and body reserve mobilization in these sows. Plasma pre- and post-prandial concentrations of amino acids in late lactation differed among the three treatment groups. Throughout lactation, litters from the 180LP and 240LP sows had a slower growth rate than litters from sows which were not restricted, suggesting that endogenous protein mobilization throughout lactation does not completely compensate for a low protein intake.

Animal Feed↗

Maternal protein restriction before pregnancy affects vital organs of offspring in Wistar rats.

Epidemiologic studies indicate that undernutrition during fetal growth can have long-term effects on adult health. However, it is not known whether these effects are also associated with maternal undernutrition before conception. The objective of the present study was to examine the effect of dietary restriction before pregnancy on the vital organs and blood parameters of offspring at different time points. Wistar female rats in the restricted group were fed a diet consisting of 80 g protein/kg for 8 weeks before pregnancy and switched to 160 g protein/kg (control) from day 0 of pregnancy, while animals from the control group were fed 160 g protein/kg throughout life. The progeny were studied at birth (n = 71), at 94 days (n = 20), and at 180 days (n = 16). Weight gain during pregnancy was significantly lower (P <.01) for dams in the restricted group. At birth, relative weight for brain was lower (P </=.008), while for kidney it was higher (P </=.008) in the restricted group compared to control. At 94 days, the relative weights of brain, liver, and heart were lower (P </=.01 for all) in the restricted group than in the control group. However, at 180 days, only liver and kidney showed lower (P </=.01 for both) relative weights. Further, in the restricted group, increases in blood glucose at 94 days and in cholesterol at 180 days were significant (P <.01 for both) in the offspring. The results thus indicate that maternal undernutrition before conception not only affected growth of vital organs, but also resulted in increased levels of glucose and cholesterol in the offspring at adulthood.

Animals↗

Stereological investigation of placental morphology in pregnancies complicated by pre-eclampsia with and without intrauterine growth restriction.

The aim of this study was to quantify placental morphology in pregnancies complicated by pre-eclampsia with and without intrauterine growth restriction. Particular attention is given to the dimensions and composition of peripheral (intermediate+terminal) villi. Placentae from 9 control pregnancies, 5 cases of pre-eclampsia, 5 cases of intrauterine growth restriction and 5 cases of pre-eclampsia with intrauterine growth restriction were randomly sampled for location and position. Formalin-fixed, wax-embedded sections stained by the Masson trichrome method were subjected to stereological analysis in order to quantify the volumes of placental components and the surfaces and derived diameters for peripheral villi and fetal capillaries. Group comparisons were drawn using two-way analysis of variance. Fetal weights were reduced in all complicated pregnancies but only intrauterine growth restriction was accompanied by a significantly smaller placenta. Pre-eclampsia was not associated with main effects on placental morphology and (except for trophoblast thickness) there were no interaction effects involving pre-eclampsia. In contrast, intrauterine growth restriction was associated with a placenta which had reduced volumes of intervillous space and all types of villi (stem, intermediate, terminal). The impoverished growth of peripheral villi affected all tissues (trophoblast, stroma, capillaries) and was accompanied by smaller exchange surface areas and a thicker trophoblastic epithelium. The derived mean diameters of villi and capillaries were not affected. It is concluded that intrauterine growth restriction, but not pre-eclampsia, is associated with substantial changes in placental morphology including impoverished growth of villi and fetal vasculature. These changes are likely to reduce placental oxygen diffusive conductances and contribute to fetal hypoxic stress.

Adult↗

Food restriction, performance, biochemical, psychological, and endocrine changes in judo athletes.

In order to test the hypothesis that dietary restriction may have a negative influence on physiological and psychological adaptation to a judo competition, we examined the effects of weight loss induced by restricting energy and fluid intake on the physiology, psychology, and physical performance of judo athletes. Twenty male judoka were randomly assigned to one of two groups (Group A: called diet, n = 10; height 174.8 +/- 1.9 cm, body weight 75.9 +/- 3.1 kg; they were asked to lose approximately 5 % of their body weight through self-determined means during the week before the competition; Group B: called control, n = 10; height 176.4 +/- 1.1 cm, body weight 73.3 +/- 6.3 kg maintained their body weight during the week before the competition). A battery of tests was performed during a baseline period (T1), on the morning of a simulated competition (T2) and 10 min after the end of the competition (T3). The test battery included assessment for body composition, performance tests, evaluation of mood, determination of metabolic and hormonal responses. Dietary data were collected using a 7-day diet record. The nutrient analysis indicated that all the athletes followed a low carbohydrate diet whatever the period of the investigation. For the Group A, the food restriction (- 4 MJ per day) resulted in significant decreases of the body weight and altered the mood by increasing Fatigue, Tension and decreasing Vigour. Dietary restriction had also a significant influence on metabolic and endocrine parameters and was associated with poor performance. After the competition, significant decreases of the levels in testosterone, T/C ratio, alkali reserve, and free fatty acid were observed in both groups, whereas the plasma concentrations in insulin, ammonia, urea, and uric acid were increased. In conclusion, our results suggest that the combination of energy restriction and intense exercise training, which causes weight reduction before a competition, adversely affects the physiology and psychology of judo athletes and impairs physical performance before the competition. Our data are the first to demonstrate that a competition including five 5-min bouts induced the same changes of physiological and psychological variables and performance whatever the dietary intake (dietary restriction or not) during the seven days before the competition.

Adult↗

Absence of association of thrombophilia polymorphisms with intrauterine growth restriction.

BACKGROUND: Previous data have demonstrated associations between thrombophilia polymorphisms in pregnant women and an increased risk of intrauterine growth restriction in their offspring, but this finding remains uncertain. METHODS: We performed a hospital-based case-control study and a family-based study including 493 newborns with intrauterine growth restriction (defined by birth weight below the 10th percentile for gestational age and sex according to Canadian norms) and 472 controls (with birth weight at or above the 10th percentile). We determined the presence or absence in newborns and their parents of the following polymorphisms: methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, factor V Leiden G1691A, and prothrombin G20210A. Mothers were interviewed to obtain information on other risk factors for intrauterine growth restriction. RESULTS: The risk of intrauterine growth restriction was not increased among mothers carrying a polymorphism associated with thrombophilia. In the case-control study, the odds ratios associated with two copies of the variant, after adjustment for newborn genotype and other risk factors, were 1.55 for MTHFR C677T (95 percent confidence interval, 0.83 to 2.90) and 0.49 for MTHFR A1298C (95 percent confidence interval, 0.25 to 0.93); heterozygotes for factor V Leiden had an odds ratio of 1.18 (95 percent confidence interval, 0.54 to 2.55), and heterozygotes for prothrombin G20210A had an odds ratio of 0.92 (95 percent confidence interval, 0.36 to 2.35). These polymorphisms in the newborn were not associated with an increased risk. Newborns who were homozygous for the MTHFR C677T variant had a decreased risk of intrauterine growth restriction (odds ratio after adjustment for mother's genotype and other confounders, 0.52 [95 percent confidence interval, 0.29 to 0.94]). The results of the family-based study supported those of the case-control study. CONCLUSIONS: Our findings do not indicate that there are associations between maternal or newborn polymorphisms associated with thrombophilia and an increased risk of intrauterine growth restriction.

Adult↗

Histologic chorioamnionitis is associated with fetal growth restriction in term and preterm infants.

OBJECTIVE: Our aim was to evaluate associations between chorioamnionitis and fetal growth restriction in infants enrolled in the Collaborative Perinatal Project. STUDY DESIGN: A total of 2579 nonanomalous, singleton infants delivered at 28 to 44 weeks' gestation with chorioamnionitis were matched 1:3 for ethnicity, gestational age, parity, and maternal cigarette use (all of which were correlated with both chorioamnionitis and markers of fetal growth restriction) with 7732 control infants. Moderate or marked leukocytic infiltrates of the placenta defined chorioamnionitis. Birth weight, length, head circumference, weight/length ratio, ponderal index, and birth weight/head circumference ratio in the lowest 5th percentile were markers of fetal growth restriction. Placental weight and the birth weight/placental weight ratio were also evaluated. RESULTS: Compared with data on matched control infants, histologic chorioamnionitis was associated with all markers of fetal growth restriction and with low birth weight/placental weight ratios (odds ratios, 1.3-1.7). The strongest associations were found at 28 to 32 weeks' gestation (odds ratios, 2.2-11). Attributable risks for several markers of fetal growth restriction exceeded 50% in infants born at <33 weeks' gestation. CONCLUSION: Histologic chorioamnionitis is associated with multiple markers of fetal growth restriction, with stronger associations noted in prematurity.

Adult↗

Responses of thyroid activity to feed restriction in the goat.

A study of the effect of restriction of feed intake on the deiodination, faecal excretion, distribution and secretion of thyroid hormones was carried out in a group of eight young male goats. In the control goats fed ad libitum no changes in the concentration of circulating thyroxine were observed with increasing age or body weight during the experimental period; however, an increase in thyroxine secretion rate per animal was apparent with increasing age or body weight of the goats. In feed-restricted goats, no changes in the peripheral deiodination of [125I]thyroxine were observed, though significantly reduced faecal excretion of [125I]thyroxine was seen in goats restricted to 50 or 20% of their ad libitum feed intake. Both thyroxine turnover rate and thyroxine distribution volume were reduced by feed restriction. The secretion rate of thyroxine was reduced to 45% of the rate in ad libitum fed animals when feed intake was restricted to 20%. Calculation of thyroxine secretion rate per kilogram 0-75 body weight showed a highly significant correlation with feed intake. It was concluded that the marked reduction in thyroid activity occurring when feed restriction was imposed would be expected to cause a physiologically significant reduction in metabolic activity.

Age Factors↗

Positive selection of primate TRIM5alpha identifies a critical species-specific retroviral restriction domain.

Primate genomes encode a variety of innate immune strategies to defend themselves against retroviruses. One of these, TRIM5alpha, can restrict diverse retroviruses in a species-specific manner. Thus, whereas rhesus TRIM5alpha can strongly restrict HIV-1, human TRIM5alpha only has weak HIV-1 restriction. The biology of TRIM5alpha restriction suggests that it is locked in an antagonistic conflict with the proteins encoding the viral capsid. Such antagonistic interactions frequently result in rapid amino acid replacements at the protein-protein interface, as each genetic entity vies for evolutionary dominance. By analyzing its evolutionary history, we find strong evidence for ancient positive selection in the primate TRIM5alpha gene. This selection is strikingly variable with some of the strongest selection occurring in the human lineage. This history suggests that TRIM5alpha evolution has been driven by antagonistic interactions with a wide variety of viruses and endogenous retroviruses that predate the origin of primate lentiviruses. A 13-aa "patch" in the SPRY protein domain bears a dense concentration of positively selected residues, potentially implicating it as an antiviral interface. By using functional studies of chimeric TRIM5alpha genes, we show that this patch is generally essential for retroviral restriction and is responsible for most of the species-specific antiretroviral restriction activity. Our study highlights the power of evolutionary analyses, in which positive selection identifies not only the age of genetic conflict but also the interaction interface where this conflict plays out.

Amino Acid Sequence↗

Protein deficiency and energy restriction in young cebus monkeys.

Infant cebus monkeys (Cebus albifrons) were fed liquid formulas that were limited in protein, energy, or a combination of the two restrictions. Weight gain, food intake, hematological development, and plasma protein and cholesterol levels were monitored over a 20-week period. The animals restricted in protein developed the classical signs of protein deficiency--reductions in plasma albumin, a mild anemia, accumulation of fat in the liver, and, in a few cases, facial edema. These animals maintained a relatively high energy intake, and apparently wasted energy when compared to similarly non-growing energy-restricted animals. Energy-restricted animals did not exhibit these symptoms, even when their daily protein intake was reduced to match that of protein-restricted monkeys. It is concluded that an energy restriction superimposed upon a limited protein intake did not increase protein requirements or precipitate protein deficiency.

Amino Acids↗

Host range restrictions of oncogenes: myc genes transform avian but not mammalian cells and mht/raf genes transform mammalian but not avian cells.

The host range of retroviral oncogenes is naturally limited by the host range of the retroviral vector. The question of whether the transforming host range of retroviral oncogenes is also restricted by the host species has not been directly addressed. Here we have tested in avian and murine host species the transforming host range of two retroviral onc genes, myc of avian carcinoma viruses MH2 and MC29 and mht/raf of avian carcinoma virus MH2 and murine sarcoma virus MSV 3611. Virus vector-mediated host restriction was bypassed by recombining viral oncogenes with retroviral vectors that can readily infect the host to be tested. It was found that, despite high expression, transforming function of retroviral myc genes is restricted to avian cells, and that of retroviral mht/raf genes is restricted to murine cells. Since retroviral oncogenes encode the same proteins as certain cellular genes, termed protooncogenes, our data must also be relevant to the oncogene hypothesis of cancer. According to this hypothesis, cancer is caused by mutation of protooncogenes. Because protooncogenes are conserved in evolution and are presumed to have conserved functions, the oncogene hypothesis assumes no host range restriction of transforming function. For example, mutated human proto-myc is postulated to cause Burkitt lymphoma, because avian retroviruses with myc genes cause cancer in birds. But there is no evidence that known mutated protooncogenes can transform human cells. The findings reported here indicate that host range restriction appears to be one of the reasons (in addition to insufficient transcriptional activation) why known, mutated protooncogenes lack transforming function in human cells.

Animals↗

The paradox of alloreactivity and self MHC restriction: quantitative analysis and statistics.

Although 1-24% of T cells are alloreactive, i.e., respond to MHC molecules encoded by a foreign haplotype, it is generally believed that T cells cannot recognize foreign peptides binding foreign MHC molecules. We show using a quantitative model that, if T cell selection and activation are affinity-driven, then an alloreactivity of 1-24% is incompatible with the textbook notion that self MHC restriction is absolute. If an average of 1% of clones are alloreactive, then according to our model, at most 20-fold more clones should, on average, be activated by antigens presented on self MHC than by antigens presented on foreign MHC. This ratio is at best 5 if alloreactivity is 5%. These results describe average properties of the murine immune system, but not the outcome of individual experiments. Using supercomputer technology, we simulated 100,000 MHC restriction experiments. Although the average restriction ratio was 7.1, restriction was absolute in 10% of the simulated experiments, greater than 100, although not absolute, in 29%, and below 6 in 24%. This extreme variability agrees with experimental estimates. Our analysis suggests that alloreactivity and average self MHC restriction both cannot be high, but that a low average restriction level is compatible with high levels in a significant number of experiments.

Animals↗

Evolutionary relationship between different subgroups of restriction endonucleases.

The type II restriction endonuclease SsoII shows sequence similarity with 10 other restriction endonucleases, among them the type IIE restriction endonuclease EcoRII, which requires binding to an effector site for efficient DNA cleavage, and the type IIF restriction endonuclease NgoMIV, which is active as a homotetramer and cleaves DNA with two recognition sites in a concerted reaction. We show here that SsoII is an orthodox type II enzyme, which is active as a homodimer and does not require activation by binding to an effector site. Nevertheless, it shares with EcoRII and NgoMIV a very similar DNA-binding site and catalytic center as shown here by a mutational analysis, indicative of an evolutionary relationship between these three enzymes. We suggest that a similar relationship exists between other orthodox type II, type IIE, and type IIF restriction endonucleases. This may explain why similarities may be more pronounced between members of different subtypes of restriction enzymes than among the members of a given subtype.

Amino Acid Motifs↗

Mva1269I: a monomeric type IIS restriction endonuclease from Micrococcus varians with two EcoRI- and FokI-like catalytic domains.

Type II restriction endonuclease Mva1269I recognizes an asymmetric DNA sequence 5'-GAATGCN / -3'/5'-NG / CATTC-3' and cuts top and bottom DNA strands at positions, indicated by the "/" symbol. Most restriction endonucleases require dimerization to cleave both strands of DNA. We found that Mva1269I is a monomer both in solution and upon binding of cognate DNA. Protein fold-recognition analysis revealed that Mva1269I comprises two "PD-(D/E)XK" domains. The N-terminal domain is related to the 5'-GAATTC-3'-specific restriction endonuclease EcoRI, whereas the C-terminal one resembles the nonspecific nuclease domain of restriction endonuclease FokI. Inactivation of the C-terminal catalytic site transformed Mva1269I into a very active bottom strand-nicking enzyme, whereas mutants in the N-terminal domain nicked the top strand, but only at elevated enzyme concentrations. We found that the cleavage of the bottom strand is a prerequisite for the cleavage of the top strand. We suggest that Mva1269I evolved the ability to recognize and to cleave its asymmetrical target by a fusion of an EcoRI-like domain, which incises the bottom strand within the target, and a FokI-like domain that completes the cleavage within the nonspecific region outside the target sequence. Our results have implications for the molecular evolution of restriction endonucleases, as well as for perspectives of engineering new restriction and nicking enzymes with asymmetric target sites.

Amino Acid Sequence↗

Adaptive changes in energy expenditure during mild and severe feed restriction in the rat.

Using a new-generation open-circuit calorimeter capable of monitoring the cost of activity, and thereby both the real thermic effect of feeding (TEF) and basal metabolism in free-moving freely-feeding rats, we have reassessed the proposal that when food intake is restricted an adaptative reduction in energy expenditure participates in the achievement of energy balance. Total energy expenditure, energy expenditure due to spontaneous activity, TEF, basal energy expenditure and respiratory quotient (RQ) were computed by indirect calorimetry in rats given either a mildly restricted (MR) feed intake for 20-30 d (17 g feed/d) or a severely restricted (SR) feed intake for 1-10 d (4 g feed/d). In MR rats no significant changes in any of the measured variables were observed. In contrast, SR rats exhibited an adaptative reduction in energy expenditure due to a reduced spontaneous activity and probably also due to a reduced basal energy expenditure. On the other hand none of the animals fed on a restricted feed intake showed an adaptative TEF decrease, suggesting that TEF under ad lib. feeding is rather an obligatory process that does not include an adaptative component. Taken together, these results point out that under restricted feeding most of the decrease in energy expenditure is associated with simple passive mechanisms, such as body weight loss, and with the reduced feed intake per se. Only under severe feed restriction can some additional energetic economy be obtained from a possible reduction of basal metabolism, and to some extent from reduced activity.

Adaptation, Physiological↗

Welfare assessment of broiler breeders that are food restricted after peak rate of lay.

1. Broiler breeder females were reared on one of three growth curves (ad libitum, conventional or modified restriction) and given rations containing a high or low concentration of crude protein. After the peak rate of lay they were fed ad libitum or a decreasing quantity of food in response to declining egg production. The welfare of the birds was assessed by determining the changes in indices of welfare at 36, 48 and 60 weeks of age. 2. Body weight increased rapidly in restricted birds fed ad libitum post-peak and water intake declined. 3. Post-peak food restriction was associated with a decrease in resting and increased drinking and spot-pecking activities. Birds that were food restricted during rearing spent more time foraging and spot-pecking at 36 and 48 but not 60 weeks of age. 4. Immune function increased with age but was not affected by the experimental treatments. The heterophil-lymphocyte ratio in birds fed ad libitum during rearing was numerically lower at 36 and higher at 48 and 60 weeks of age compared with restricted birds. 5. There was no effect of treatment on plasma corticosterone concentration. Creatine kinase activity was high at 60 weeks in treatments that were characterised by poor reproductive status and the activities of other enzymes reflected differences in reproductive status and mortality. 6. There was no long-term welfare or production advantage from feeding low protein rations or more generous feeding during the rearing period compared with conventional food restriction programmes.

Animal Husbandry↗

Production responses of layer strain hens to food restriction during rearing.

Production responses of laying hens to food restriction during rearing were measured in two trials. Food was restricted by two methods: time restriction (TR, food continuously available for 24 to 30 h each 72 h) and proportion restriction (PR, daily allocations of about 60 to 70% of that consumed by ad libitum fed birds (F]. The rearing treatments were applied from 42 to 162 d and from 56 to 168 d of age in experiments 1 and 2 respectively. All birds were fed ad libitum in the laying period to 437 d and 476 d of age in experiments 1 and 2 respectively. Body weight was reduced significantly in both experiments by both methods of restriction, but more so by TR. Marked compensatory growth accompanied the high food intake following the end of food restriction. There was a significant increase in average egg weight concommitant with a change in the relationship between egg weight and age. Possibly this is due to an altered pattern of food intake at onset of lay.

Age Factors↗

Plasma growth hormone and insulin-like growth factor-I (IGF-I) concentrations at the onset of lay in ad libitum and restricted broiler breeder fowl.

1. Plasma concentrations of growth hormone (GH) and insulin-like growth factor I(IGF-I) were determined in individually caged broiler breeder females from 17 to 30 weeks of age. The birds were fed ad libitum or restricted during rearing in a randomised block design. Restricted birds were fed ad libitum after laying an egg and egg production was recorded to 54 weeks. 2. GH concentrations were higher in restricted compared with ad libitum-fed birds at 17 to 21 weeks of age and were similar thereafter. Plasma IGF-I concentrations were higher in restricted compared with ad libitum-fed birds throughout the sampling period of the experiment. 3. The age at first egg was delayed by about two weeks in restricted birds. At 54 weeks of age they had laid 114 compared with 67 eggs in birds fed ad libitum throughout and had produced less than half the number of eggs with defective shells. 4. It was suggested that differences in egg production between ad libitum and restricted broiler breeder females could be related to changes in the pattern of GH and/or IGF-I secretion.

Aging↗