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PubMed1978

Comparison of the effects of keto acid analogues and essential amino acids on nitrogen homeostasis in uremic patients on moderately protein-restricted diets.

Comparisons of isonitrogenous supplements (1.2 g N) of essential amino acids and five keto acid analogues with four essential amino acids were made in seven patients with stable chronic renal failure (creatinine clearance, 4.6 to 16 ml/min) on moderately protein-restricted diets (4.60 to 7.8 g N per day). Full nitrogen balance data on the four patients who have already completed studies lasting 24 weeks are presented. No benefits of keto acid over amino acid supplements were observed. Two transient episodes of hypercalcemia occurred during keto acid treatment. There was no improvement of renal function with keto acids. Also, no carry-over effects were seen after keto acid treatment. It is concluded that any beneficial effects of keto acids in patients with chronic renal failure are only likely to occur in those taking a diet of less than 30 g protein daily.

Adult↗

PubMed1979

Influence of prenatal and continuous postnatal protein-deficient diets on the development of rats.

The influence of prenatal and continuous postnatal protein-restricted diet on the development of rats was investigated. Virgin female rats were maintained for 35 days on isocaloric diets containing 8 or 25% casein, and then mated. The animals were supplied their respective diets during gestation and nursing. It was observed that the offspring of mothers kept on the 8% casein diet had 50% less body weight, and 10-15% less brain weight than the corresponding controls. The peak of rapid brain growth for both groups of animals occurred at age 6 days. The rate of de novo biosynthesis of sterols, following the injection of (2-14C)-mevalonic acid into the midline thalamic area and the cerebellum, was also investigated. A significant shift of the age of peaking of 14C-incorporation into sterols in the cerebellum was noted. Our results indicate that although unlimited amounts of food were supplied to the mothers on the 8% casein diet, this could not offset the detrimental effect of the protein deficiency on the offspring.

Animals↗

PubMed1978

[Diets for patients with kidney diseases].

Dietary treatment is indicated in the conservative management of chronic renal failure and in patients on maintenance dialysis. Water, sodium and potassium warrant chief consideration. The principles and different forms of protein-restricted diets are discussed.

Acute Kidney Injury↗

PubMed1979

Influence of dietary protein restriction on ovulation, fertilization rates and pre-implantation embryonic development in mice.

Eggs were recovered from 153 adult female mice fed either a normal (27% protein) or a protein-deficient (8% protein) diet from day 15 (Group I) or 30 (Group II) before mating until sacrifice. The females were mated with fertile males and sacrificed 48, 72, 96 or 120 hours after observation of vaginal plugs. The study was performed with females that ovulated spontaneously and with females induced to ovulate by injection of pregnant mare's serum gonadotrophin and human chorionic gonadotrophin. Without gonadotrophin treatment, significantly fewer eggs were recovered from malnourished than from normal females. However, after hormonal treatment, the number of eggs ovulated by malnourished and normal females increased similarly. About 50% of the eggs recovered from malnourished females in both groups I and II were cleaved whereas 90% of the eggs recovered from well-nourished females were cleaved. The development of the cleaved eggs from protein deficient females was delayed and asynchronous in comparison with that of eggs from normal females. Embryos recovered from malnourished females also were retarded in differentiation of morulae to blastocysts. It is concluded that a protein-restricted diet adversely affects the fertilization of eggs as well as their early development and differentiation.

Animals↗

PubMed1978

Protein restriction in the conservative management of uremia.

Protein-restricted diets are widely used in the dietary management of uremia. These diets are undoubtedly effective in ameliorating many aspects of the uremic syndrome. However, there is no consensus as to whether diets providing less than 0.6 g/kg per day of protein are nutritionally adequate and capable of preventing the wasting syndrome. Wasting is common in the adult patient with renal insufficiency as is growth failure in the uremic child. There is some evidence that wasted patients do less well on hemodialysis and are more prone to infection. Experimental studies in uremic animals point ot diminihsed efficiency of utilization of protein, increased gluconeogenesis from animo acids, and increased catabolism of protein in the fasting state; in addition, the metabolism of a number of individual amino acids is altered in uremia. In view of these multiple abnormalities, it would seem unwise to routinely provide less than the Recommended Daily Allowances of protein. More recent developments, i.e., supplementation of essential amino acids and perhaps alpha keto acids, may provide useful alternatives. One important aspect of dietary management, i.e. prevention of hyperlipidemia, has attracted surprisingly little attention so far. Therapy with protein restricted diets in nondialyzed uremic patients has to compete with other modalities of treatment currently available, i.e., hemodialysis and transplantation, in providing optimal medical rehabilitaiton of the patient.

Adult↗

PubMed2026

Dietary effects on cytosolic and mitochondrial tRNA abundance and modification patterns across mouse tissues.

Transfer RNAs (tRNAs) are central to protein synthesis and are increasingly recognized as dynamic regulators of gene expression whose abundance and chemical modifications are subject to precise biological control. Here, we systematically investigate how two distinct dietary interventions, low-protein and high-fat diets, reshape the tRNA landscape across multiple mouse tissues, using RNA mass spectrometry and ordered two-template relay sequencing (OTTR-seq) to comprehensively profile cytosolic and mitochondrial tRNAs at single-nucleotide resolution. We reveal pronounced tissue-specific biases in tRNA isodecoder expression, including the unexpected presence of full-length cytosolic tRNAs in mature sperm with a distinct isotype composition. In somatic tissues such as liver and heart, dietary conditions alter both tRNA abundance and key modifications known to regulate decoding efficiency, whereas in reproductive tissues diet primarily affects the abundance of select tRNAs with comparatively limited changes in modification profiles. We further demonstrate that mitochondrial tRNAs are subject to diet-responsive changes in both abundance and modification status and that even subtle differences in dietary fat composition are sufficient to alter tRNA modification signatures. Together, these findings establish the tRNA epitranscriptome as a sensitive and tissue-specific sensor of nutritional state and provide a resource for understanding how dietary cues interface with translational regulation in somatic and reproductive tissues.

Male↗

PubMed1977

Differential responses to prenatal malnutrition among neonatal rats.

Female rats were fed (A) protein-restricted diet 1 month prior to mating and throughout pregnancy, or (B) protein-free diet during 10-20 days of pregnancy. At birth, four parameters of the offspring, body weight, cerebral weight, cerebral DNA, and cerebral protein were well correlated with each other, and were significantly lower than in the controls fed stock diet. The malnourished population had on the average 30-70% "outstanding low" individuals (parameter values more than 2 SD below the mean of the control); this is 13-20 times more than in the control. Even in malnourished populations a certain number of individuals escaped malnutrition (parameter values not lower than the mean of the control): they appear to be those which in normal populations would be well above the average. These individuals escaped malnutrition not by taking advantage of their littermates: the latter, though malnourished, were still better than the average in the malnourished group. The mechanisms by which some of the malnourished females differentially provide enough nutrients for one of their fetuses, and more than the average for its littermates, may involve differential mobilization of maternal nutrient among individual mothers, as well as differential blood supply to individual placentas or placental transfer to individual fetuses.

Animal Nutritional Physiological Phenomena↗

PubMed1977

Plasma amino acid patterns in hepatic encephalopathy of differing etiology.

Plasma amino acids were measured in 18 patients with hepatic encephalopathy on a protein-restricted diet of 20 g or less daily. Plasma aminograms tended to group into two distinct patterns depending on the etiology of the patients' hepatic pathology. Patients with chronic liver disease with superimposed acute insults, i.e., gastrointestinal bleeding, infection, alcoholic hepatitis, had elevated levels of the aromatic amino acids, phenylalanine, tyrosine, and tryptophan, as well as methionine, glutamate, and aspartate, whereas levels of the branched chain amino acids, valine, leucine, and isoleucine, were consistently depressed. Those patients with previously normal livers and acute hepatic necrosis, i.e., "fulminant hepatitis," had grossly elevated levels of all amino acids except the branched chain amino acids, which were normal. Elevations of amino acid levels in this patient group tended to correlate with extent of hepatic necrosis and hence had prognostic significance. Additionally, the different patterns seen in these two groups tend to suggest the indicated therapy as well as predict its efficacy.

Acute Disease↗

PubMed2026

Risk factors for loss of skeletal muscle mass in patients with chronic kidney disease on a low-protein diet.

OBJECTIVES: A low-protein diet (LPD) is recommended for patients with chronic kidney disease (CKD) to prevent a further decline in renal function. However, its impact on muscle mass in these patients remains unclear. This study investigated the risk factors for loss of muscle mass in patients with CKD on an LPD. METHODS: Eighty-four patients with predialysis CKD (59 men, mean age 61.9 ± 11.5 y) who participated in a multicenter randomized controlled trial initiated in 2014 were retrospectively reviewed. We collected data on baseline blood and urine tests, body composition, and dietary records at the start and end of the observation period. We evaluated muscle mass using the skeletal muscle index (SMI) and analyzed risk factors for a decrease in SMI during the 24-wk observation period, using logistic regression analysis. Variables with an association (P < 0.1) in univariate analysis, as well as age, sex, use of low-protein rice, and changes in protein intake, were subjected to multivariate analysis. RESULTS: SMI decreased in 50 patients (59.5%) during the observation period. Multivariate analysis identified significant associations of the SMI with serum albumin at baseline (odds ratio 0.11, 95% confidence interval 0.02-0.52, P = 0.004) and changes in energy intake while on the LPD (odds ratio 3.39, 95% confidence interval 1.00-11.43, P = 0.049). CONCLUSIONS: Risk factors for reduced SMI in patients with CKD on an LPD were malnutrition when initiating the LPD and reduced energy intake during its implementation. Clinicians should optimize nutritional status before initiation of an LPD and ensure adequate energy intake throughout treatment.

Humans↗

PubMed1977

Effect of dietary protein restriction or food restriction on oxygen consumption and mitochondrial distribution in cardiac and red and white skeletal muscle of rats.

The effects of food restriction and dietary protein restriction on the oxygen consumption of three types of muscle in the rat were compared. Control rats were fed a diet containing 27% casein. Two groups of protein-restricted rats were fed isoenergy diets containing 15% or 8% casein. Two groups of food-restricted rats were fed either the 27% or 15% casein diets in amounts equivalent to 35% of the intake of energy. Oxygen consumption was measured in papillary muscle and in fibers from the red (high oxidative) and white (low oxidative) portions of the quadriceps with pyruvate and malate as substrates. Control values (micronlO2/g dry wt/min) were 35.2 + 1.5 (papillary), 20.7+/-1.9 (red), and 7.8+/-0.7 (white). Restriction of dietary protein content failed to alter the oxygen consumption of any of the muscle types. In contrast, involuntary food restriction,combined with a reduction in protein content, caused a reduction in the oxygen consumption of papilary and white skeletal muscle, but the metabolism of red skeletal muscle was not affected. No differences were found in the appearance and distribution of mitochondria in cardiac or red skeletal muscle after examination by electron microscopy, but a depletion of subsarcolemmal mitochondria was evident in white muscle from the food-restricted rats.

Animals↗

PubMed1975

Effects of dietary protein restriction and glucocorticoid administration on urea excretion in rats.

Rats were sampled for clearance studies under anesthesia after 0, 2, 4, 7 and 14 days of dietary protein restriction. Mean fractional urea excretion decreased between day 2 and day 7 of protein restriction after a two-day lag in response. Seven-day administration of dexamethasone in protein-restricted rats caused a significant increase in mean fractional urea excretion. Adrenalectomized rats fed a normal diet had fractional urea excretion values resembling those in protein-restricted rats. Chronic administration of dexamethasone in adrenalectomized rats caused a consistent increase in fractional urea excretion. Fractional urea excretion values were no lower in protein-restricted adrenalectomized rats fed a normal diet. The mean plasma corticosterone concentration (measured 6 to 8 PM) was decreased in rats fed a low protein diet relative to rats fed a high protein diet. The results suggest that glucocorticoids may play a role in the tubular regulation of urea excretion either by a direct effect on the renal tubule or through some intermediate factor. A mediating role of glomerular filtration rate in glucocorticoid-induced changes of fractional urea excretion could not be ruled out, however.

Adrenalectomy↗

PubMed1977

Amino acid incorporation into total protein and levels of S-100 protein in discrete rat brain areas after prolonged protein or amino acid restriction.

Young adult rats were fed an isocaloric diet for 28 days. The diet consisted of either 22% casein, or protein-restricted food consisting of a 5% mixture of soy and whey protein, or a synthetic amino acid mixed diet devoid of the essential amino acids tryptophan, valine, lysine, and threonine. The level of the nervous tissue-specific S-100 protein was quantified immunoelectrophoretically in 9 different brain areas. A marked decrease of S-100 was observed in hippocampus and posterior part of the cerebellar vermis per g wet weight in protein-restricted rats. An additional lowering was noticed in sensory motor cortex per mg soluble protein. This effect was potentiated with the amino acid-deficient diet. The in vitro incorporation of 3H-leucine into cerebellar proteins was slightly decreased in the low-protein-fed rats, and more markedly decreased in those receiving an amino acid-restricted diet.

Amino Acids↗

PubMed1978

Immune response in malnutrition. Effect of protein deficiency on the DNA synthetic response to alloantigens.

To evaluate the DNA synthetic response to alloantigens by lymphocytes from mice fed diets with normal (27%) and low (8%) protein content, we quantitated the uptake of 125IUDR in spleens of lethally irradiated adult F1 hybrids injected with cells with parental C57BL/6 donors kept on either diet. Thymocytes, spleen and lymph node cells from protein-restricted parental mice synthesized higher amounts of DNA than those from normally fed controls. Added thymocytes from either malnourished or normal F1 hybrids had similar inhibitory effects on the response of an active parental inoculum. The results indicate that cells from mice kept on a moderately protein-deficient diet for 3--5 weeks after weaning, have increased capacity to proliferate in response to alloantigens, suggesting a high proportion of reactive cells and/or changes in the ratio of the interacting cell populations in their lymphoid organs.

DNA↗

PubMed1975

Effect of maternal protein deprivation on enzymatic development in newborn rats.

Postnatal development of liver tyrosine aminotransferase and glucose-6-phosphatase, expressed as activity per gram of liver, occurred as rapidly in pups from pregnant rats fed throughout gestation a diet containing only 4% of casein as in pups from those fed the control diet containing 18% of casein supplemented with 0.3% of L-methionine. Total enzyme activity per liver was lower in pups from protein-restricted dams due to their smaller liver size. Dams fed the 4% casein diet during pregnancy gained much less weight than those fed the control diet and produced pups that weighed significantly less than control pups. Reproductive performance of a few dams fed 6% casein diets with or without amino acid supplements during gestation was comparable to that of dams fed the control diet. Litter size was not significantly reduced by the low-protein intake.

Animals↗

PubMed1977

Changes within vascular bundles of rodent kidneys caused by different diets.

Morphological effects caused by two different diets (low protein-high water intake, and high protein-restricted water) on the vascular bundles in the outer medullary zone of the kidney were studied in the laboratory white mouse and in the golden spiny mouse (Acomys russatus, Muridae). In both rodents, when on a low protein-high water intake diet, considerable interstitial substance was found between the vasa recta of the bundles. No interstitial substance was found in animals on high protein-low water intake diet; as a result the vasa recta of the vascular bundle adhered closely. The low protein-high water intake diet caused a marked diuresis, low urine osmolality and low urinary urea concentration. It is assumed that the increase in interstitial substance between the vasa recta of the vascular bundle lowers the efficiency of the counter current barrier system for urea in the kidney and, as a consequence, the medullary urea gradient and urine concentrating capacity decreases. In animals on a high protein diet, the closely juxtaposed vasa recta assure an efficient countercurrent exchange, leading to accumulation and maintenance of a large urea gradient in the medulla and maximal urine concentration. It is suggested that the amount of interstitial material between the vasa recta of the vascular bundle might serve as a modulating factor for the urea concentration in the kidney.

Animal Nutritional Physiological Phenomena↗

PubMed1975

Effect of different regimens of early malnutrition on behavioural development and adult avoidance learning in Swiss white mice.

1. The effects of perinatal malnutrition on behavioural development and adult shuttle-box avoidance performance were studied in Swiss white mice. 2. Mice were malnourished (a) from the 7th day of gestation until birth, (b) from birth until weaning, or (c) during both gestation and the sucking period. 3. Pups born of protein-restricted mothers had reduced birth weights, retarded development and poor adult avoidance performance, even if reared from birth by well-nourished mothers. 4. Postnatal malnutrition, induced either by restricting maternal diet or by rearing in large litters, retarded development during the second half of lactation and lowered subsequent adult avoidance performance.

Animal Nutritional Physiological Phenomena↗

PubMed1977

Protein and calorie malnutrition in infant cebus monkeys: growth and behavioral development during deprivation and rehabilitation.

The growth and development of 32 cebus monkeys were studied during a period of insult in nutritional or rearing conditions and after rehabilitation. Eight experimental groups of four animals each were subjected to one of four diets--control, protein restricted, calorie restricted, and protein-calorie restricted, and one of two rearing conditions-partial isolation or a comparatively enriched condition-in a 4 x 2 factorial design. The period of insult from 2 to 6 months of age was followed by 6 months of rehabilitation in both diet and rearing conditions. It was found that only diet affected physical growth, but both diet and rearing affected behavioral development and exploratory behavior. Whereas calorie deficiency produced a direct effect on behavior independent of rearing conditions, protein deficiency produced an effect only in combination with rearing restriction. The effect of protein-calorie deficiency had some characteristics in common with each of the other deficiencies. Retardation in rate of behavioral development was less severe than retardation in growth, most notably in the protein-restricted, enriched-rearing group, producing animals who were behaviorally mature for their size. All groups caught up in physical growth during rehabilitation but the protein-calorie restricted groups failed to recuperate completely in exploratory behavior.

Animals↗

PubMed1978

Hepatic transaminase in protein-restricted rats: development of a controlled model.

A marginal protein malnutrition model which makes allowances for the increasing nutritional requirements of the growing rat and the effects of dietary manipulation on diurnal rhythms, while still rigidly controlling the level of protein restriction, is reported. A predetermined, constantly increasing intake of four purified diets, providing approximately 40 to 160% of the National Research Council protein requirement for rats was fed to rats receiving a nitrogen-free energy source adlibitum. This standardization reduced within-group variation and allowed precise growth reproducibility. Biochemical parameters were measured at evenly spaced intervals throughout the day to remove diurnal differences from between-group comparisons. Growth, nitrogen balance, and 24-hour means of liver weight, DNA, RNA, protein, and glutamate-oxaloacetate and glutamate-pyruvate transaminases reflected protein intake. However, when growth was depressed 10, 30, or 60%, liver GPT/DNA was depressed 40, 49, or 67%, respectively. Hepatic GPT appears to be a sensitive and accurate indicator of marginal protein malnutrition.

Alanine Transaminase↗