Changes In Dietary Protein Intake Research Articles

Dietary protein load affects the energy and nitrogen balance requiring liver glutamate dehydrogenase to maintain physical activity

Provision of amino acids to the liver is instrumental for gluconeogenesis while it requires safe disposal of the amino group. The mitochondrial enzyme glutamate dehydrogenase (GDH) is central for hepatic ammonia detoxification by deaminating excessive amino acids towards ureagenesis and preventing hyperammonemia. The present study investigated the early adaptive responses to changes in dietary protein intake in control mice and liver-specific GDH knockout mice (Hep-Glud1-/-). Mice were fed chow diets with a wide coverage of protein contents; i.e. suboptimal 10%, standard 20%, over optimal 30%, and high 45% protein diets; switched every 4 days. Metabolic adaptations of the mice were assessed in calorimetric chambers before tissue collection and analyses. Hep-Glud1-/- mice exhibited impaired alanine induced gluconeogenesis and constitutive hyperammonemia. The expression and activity of GDH in liver lysates were not significantly changed by the different diets. However, applying an in situ redox-sensitive assay on cryopreserved tissue sections revealed higher hepatic GDH activity in mice fed the high-protein diets. On the same section series, immunohistochemistry provided corresponding mapping of the GDH expression. Cosinor analysis from calorimetric chambers showed that the circadian rhythm of food intake and energy expenditure was altered in Hep-Glud1-/- mice. In control mice, energy expenditure shifted from carbohydrate to amino acid oxidation when diet was switched to high protein content. This shift was impaired in Hep-Glud1-/- mice and consequently the spontaneous physical activity was markedly reduced in GDH knockout mice. These data highlight the central role of liver GDH in the energy balance adaptation to dietary proteins.

Longitudinal association between dietary protein intake and survival in peritoneal dialysis patients

Background Decreased dietary protein intake (DPI) may lead to protein-energy malnutrition and may be associated with increased mortality risk. We hypothesized that longitudinal changes in dietary protein intake have independent associations with survival in peritoneal dialysis (PD) patients. Methods 668 stable PD patients were selected in the study from January 2006 to January 2018 and were followed up until December 2019. Their three-day dietary records were collected at the baseline (the sixth month after PD) and thereafter every 3 months for two and a half years. The latent class mixed models (LCMM) were used to identify subgroups of PD patients with similar longitudinal trajectories of DPI. The relation between DPI (baseline and longitudinal data) and survival was examined using Cox model to estimate death hazard ratios. Meanwhile, different formulae were used to assess nitrogen balance. Results The results showed that baseline DPI ≤ 0.60g/kg/day was associated with the worst outcome in PD patients. Patients with DPI 0.80–0.99g/kg/day and DPI ≥ 1.0g/kg/day both presented positive nitrogen balance; patients with DPI 0.61–0.79g/kg/day presented obviously negative nitrogen balance. Longitudinal association between time-dependent DPI and survival was found in PD patients. The consistently low DPI' (0.61–0.79g/kg/d) group was correlated with increased death risk as compared with the 'consistently median DPI' group (0.80–0.99g/kg/d, HR = 1.59, p = 0.008), whereas there was no difference in survival between 'consistently median DPI' group and 'high-level DPI' group (≥1.0 g/kg/d, p > 0.05). Conclusion Our study revealed that DPI ≥ 0.8 g/kg/day was beneficial to the long-term outcome for the PD population.

Gut-Immune-Kidney Axis: Influence of Dietary Protein in Salt-Sensitive Hypertension.

Humans with salt-sensitive hypertension demonstrate increased morbidity, increased mortality, and renal end-organ damage when compared with normotensive subjects or those with salt-resistant hypertension. Substantial evidence from humans and animals has also demonstrated the role of dietary components other than salt to modulate hypertension. Evidence presented in this review provides support for the view that immunity and inflammation serve to amplify the development of salt-sensitive hypertension and leads to malignant disease accompanied by end-organ damage. Interestingly, salt-sensitive disease is modulated by changes in dietary protein intake, which also influences immune mechanisms. Together, the evidence presented in this review from animal and human studies indicates that changes in dietary protein source have profound effects on the gut microbiota, microbiota-derived metabolites, DNA methylation, gene expression, immune cell activation, the production of cytokines and other factors, and the development of salt-sensitive hypertension and related disease phenotypes.

Changes in Dietary Protein Intake and Outcomes Among Patients with CKD

Changes in Dietary Protein Intake and Outcomes Among Patients with CKD

Protein Intake at Twice the RDA in Older Men Increases Circulatory Concentrations of the Microbiome Metabolite Trimethylamine-N-Oxide (TMAO).

Higher dietary protein intake is increasingly recommended for the elderly; however, high protein diets have also been linked to increased cardiovascular disease (CVD) risk. Trimethylamine-N-oxide (TMAO) is a bacterial metabolite derived from choline and carnitine abundant from animal protein-rich foods. TMAO may be a novel biomarker for heightened CVD risk. The purpose of this study was to assess the impact of a high protein diet on TMAO. Healthy men (74.2 ± 3.6 years, n = 29) were randomised to consume the recommended dietary allowance of protein (RDA: 0.8 g protein/kg bodyweight/day) or twice the RDA (2RDA) as part of a supplied diet for 10 weeks. Fasting blood samples were collected pre- and post-intervention for measurement of TMAO, blood lipids, glucose tolerance, insulin sensitivity, and inflammatory biomarkers. An oral glucose tolerance test was also performed. In comparison with RDA, the 2RDA diet increased circulatory TMAO (p = 0.002) but unexpectedly decreased renal excretion of TMAO (p = 0.003). LDL cholesterol was increased in 2RDA compared to RDA (p = 0.049), but no differences in other biomarkers of CVD risk and insulin sensitivity were evident between groups. In conclusion, circulatory TMAO is responsive to changes in dietary protein intake in older healthy males.

AMP-activated protein kinase signaling regulated expression of urea cycle enzymes in response to changes in dietary protein intake.

Abundance of urea cycle enzymes in the liver is regulated by dietary protein intake. Although urea cycle enzyme levels rise in response to a high-protein (HP) diet, signaling networks that sense dietary protein intake and trigger changes in expression of urea cycle genes have not been identified. The aim of this study was to identify signaling pathway(s) that respond to changes in protein intake and regulate expression of urea cycle genes in mice and human hepatocytes. Mice were adapted to either HP or low-protein diets followed by isolation of liver protein and mRNA and integrated analysis of the proteomic and transcriptomic data. HP diet led to increased expression of mRNA and enzymes in amino acid degradation pathways and decreased expression of mRNA and enzymes in carbohydrate and fat metabolism, which implicated adenosine monophosphate-activated protein kinase (AMPK) as a possible regulator. Primary human hepatocytes, treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) an activator of AMPK, were used to test whether AMPK regulates expression of urea cycle genes. The abundance of carbamoylphosphate synthetase 1 and ornithine transcarbamylase mRNA increased in hepatocytes treated with AICAR, which supports a role for AMPK signaling in regulation of the urea cycle. Because AMPK is either a target of drugs used to treat type-2 diabetes, these drugs might increase the expression of urea cycle enzymes in patients with partial urea cycle disorders, which could be the basis of a new therapeutic approach.

Glucagon infusion alters the hyperpolarized 13 C-urea renal hemodynamic signature.

Renal urea handling is central to the urine concentrating mechanism, and as such the ability to image urea transport in the kidney is an important potential imaging biomarker for renal functional assessment. Glucagon levels associated with changes in dietary protein intake have been shown to influence renal urea handling; however, the exact mechanism has still to be fully understood. Here we investigate renal function and osmolite distribution using [13 C,15 N] urea dynamics and 23 Na distribution before and 60min after glucagon infusion in six female rats. Glucagon infusion increased the renal [13 C,15 N] urea mean transit time by 14%, while no change was seen in the sodium distribution, glomerular filtration rate or oxygen consumption. This change is related to the well-known effect of increased urea excretion associated with glucagon infusion, independent of renal functional effects. This study demonstrates for the first time that hyperpolarized 13 C-urea enables monitoring of renal urinary excretion effects in vivo.

Proximal tubule glutamine synthetase expression is necessary for the normal response to dietary protein restriction.

Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion changes in parallel during changes in dietary protein intake. Dietary protein restriction decreases endogenous acid production and decreases urinary ammonia excretion, a major component of net acid excretion. Glutamine synthetase (GS) catalyzes the reaction of [Formula: see text] and glutamate, which regenerates the essential amino acid glutamine and decreases net ammonia generation. Because renal proximal tubule GS expression increases during dietary protein restriction, this could contribute to the decreased ammonia excretion. The purpose of the current study was to determine the role of proximal tubule GS in the renal response to protein restriction. We generated mice with proximal tubule-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Cre-negative (Control) and PT-GS-KO mice in metabolic cages were provided 20% protein diet for 2 days and were then changed to low-protein (6%) diet for the next 7 days. Additional PT-GS-KO mice were maintained on 20% protein diet. Dietary protein restriction caused a rapid decrease in urinary ammonia excretion in both genotypes, but PT-GS-KO blunted this adaptive response significantly. This occurred despite no significant genotype-dependent differences in urinary pH or in serum electrolytes. There were no significant differences between Control and PT-GS-KO mice in expression of multiple other proteins involved in renal ammonia handling. We conclude that proximal tubule GS expression is necessary for the appropriate decrease in ammonia excretion during dietary protein restriction.

Relationship between dietary protein intake and the changes in creatinine clearance and glomerular cross-sectional area in patients with IgA nephropathy.

Dietary protein intake (PI) induces glomerular hyperfiltration and reduced dietary PI can be effective in preserving kidney function. However, there is limited information regarding the relationship between dietary PI and glomerular histological changes in chronic kidney disease. We investigated the relationship between changes in dietary PI and both the changes in creatinine clearance and glomerular histomorphometry in adult patients with IgA nephropathy (IgAN). A total of 24 consecutive adult patients with biopsy-confirmed IgAN were enrolled and glomerular histomorphometric variables and clinical variables were investigated. The main clinical variables were differences in creatinine clearance (Ccr) (dCcr) and in PI (dPI) which were calculated by subtracting PI and Ccr values in patients on a controlled diet during hospitalization for kidney biopsy from the respective values in patients on daily diets as outpatients. These values of PI were estimated from urinary urea excretion measured by 24-h urine collection. The main renal histomorphometric variable was glomerular tuft area (GTA) (μm(2)). dCcr positively correlated with dPI (r = 0.726, P < 0.001). GTA correlated positively with dPI (r = 0.556, P = 0.013). Multiple regression analysis showed that dPI was independently associated with both dCcr and GTA. Additionally, GTA positively correlated with dietary PI as outpatients (r = 0.457, P = 0.043). Changes in dietary PI were associated with the changes in glomerular filtration rate. Furthermore, histomorphometric findings suggested that a greater dietary PI can affect the glomerular size at the time of the initial diagnostic biopsy for IgAN.

Changes in dietary protein intake differentially affect glucose tolerance and lipid profile in adults with impaired versus normal glucose tolerance

The effects of changes in total protein intake (PRO) on oral glucose tolerance (GT) and lipid‐lipoprotein profile (LLP) were studied in 136 overweight/obese 35–65y, free feeding adults who consumed supplements with 400 kcal/d and 0, 20, 40 or 60 g/d whey protein and exercised 3d/week for 9 months. Retrospectively, subjects were divided into impaired GT (baseline 2‐h glucose &gt; 140 mg/dL) and normal GT groups. Insulin sensitivity was assessed by the Homeostatic Model Assessment (HOMA: 405/(glucosef (mg/dL) • insulinf (U/L)). A multiple regression model assessed the moderating effects of impaired GT on the impact of change in PRO on the GT, HOMA and LLP parameters (adjusted for weight change and gender). A change in PRO was positively associated with changes in HOMA, fasting triacylglycerol (p&lt;0.05) and fasting insulin (p=0.060) in the GT impaired group only (group by PRO, p &lt; 0.05, &lt; 0.05 and 0.061). Change in PRO was not associated with changes in glucose and insulin responses to a 75‐g oral glucose tolerance challenge, or changes in total cholesterol and HDL. In summary, while most research has focused on the effects of total protein intake on health‐related outcomes, these results indicate that the change in protein intake is also important to consider when helping overweight/obese adults with impaired glucose tolerance improve their health.Support: US Whey Protein Res Consort; NIH T32AG025671 and UL1 RR025761

Changes in dietary protein intake has no effect on serum cystatin C levels independent of the glomerular filtration rate

Cystatin C is being considered as a replacement for serum creatinine in the estimation of the glomerular filtration rate (GFR); however, its plasma levels might be affected by factors other than the GFR, such as protein intake. We performed a post hoc analysis of the data in the Modification of Diet in Renal Disease study, in which we compared serum creatinine and cystatin C levels in 741 patients with available estimates of protein intake at baseline prior to their randomization to diets containing various amounts of protein, and at 2 years of follow-up in 426 of these patients in whom a cystatin C measurement was available. The 503 patients in study A (GFR 25-55 ml/min per 1.73 m(2)) had been assigned a low (0.58 g/kg per day) or a usual (1.3 g/kg per day) protein intake, and the 238 participants in study B (GFR 13-24 ml/min per 1.73 m(2)) were assigned a very low (0.28 g/kg per day) or the low protein intake. In either study group, lowering the dietary protein intake reduced the change in creatinine, but did not have a significant change in cystatin C. Thus, in patients with moderate-to-severe chronic kidney disease, serum cystatin C unlike serum creatinine was not affected by dietary protein intake independent of changes in GFR. Hence, cystatin C may allow more accurate estimates of GFR than creatinine for patients with reduced protein intake. Further study of other non-GFR determinants of cystatin C is needed before the widespread adoption.

Cerebrospinal fluid concentrations of large neutral and basic amino acids in Macaca mulatta: diurnal variations and responses to chronic changes in dietary protein intake

In rats, dietary protein intake influences brain concentrations of tryptophan, tyrosine, and other large neutral amino acids (LNAAs) and the neurotransmitters to which they are linked. Few experiments have examined these dietary protein–amino acid relationships in nonhuman primates, in relation to time of day or dietary protein content. We therefore examined the effect in monkeys of changes in chronic protein intake on 24-hour plasma and cerebrospinal fluid (CSF) concentrations of LNAAs (tyrosine, phenylalanine, branched-chain amino acids) and basic amino acids. Juvenile male monkeys ( Macaca mulatta) consumed for sequential 4-week periods diets differing in protein content (∼23% → ∼16% → ∼10% → ∼6% protein [percentage of energy]). The daily ration was presented as a morning meal of fruit and an afternoon meal of fruit and a commercial diet to mimic feeding patterns in the wild. During week 4 on each diet, blood and CSF were sampled repeatedly over a 48-hour period via indwelling catheters. Plasma and CSF LNAA concentrations varied markedly with time of day and dietary protein content, showing up to 4-fold variations. Diurnal variations in plasma and CSF basic amino acids were smaller in magnitude and generally not strongly linked to dietary protein content. A measure of the competitive transport of LNAAs across the blood-brain barrier, calculated using plasma concentrations of the LNAAs and their blood-brain barrier kinetic constants, predicted the observed CSF concentration of each LNAA examined remarkably well, except for phenylalanine. Based on observations in rats, the variations in the CSF concentrations of the LNAAs in monkeys may be large enough to influence metabolic and signaling pathways in brain to which they have been linked.

White or red clover-grass silage in organic dairy milk production: Grassland productivity and milk production responses with different levels of concentrate

Red (RC) or white (WC) clover were grown in mixture with grasses, ensiled and offered to dairy cows in early lactation over two successive years (48 cows per year) to compare grassland yield, feed intake, milk production and milk quality. The crops were ensiled in round bales and proportional mixtures of the second and third cut prepared each year were used to ensure that the silage treatments were representative of the crop. In addition to silage type, concentrate supplementation, without and with (10 kg/day), was included as a factor in a 2 × 2 factorial, continuous experiment. Total dry matter (DM) yield, silage chemical composition and total DM intake was hardly affected by silage type. There was no effect of silage type on milk yield and milk constituents either, except for higher milk protein content ( P < 0.05) on WC and higher milk fat content of C18:3 n-3 ( P < 0.001), C18:2 n-6 ( P < 0.05) fatty acids (FAs) and sum of polyunsaturated FA ( P < 0.001) and lower n-6/ n-3 FA ratio ( P < 0.01) on RC. Concentrate supplementation increased total DM, N and net energy intakes ( P < 0.001), milk yield ( P < 0.001), milk fat ( P < 0.01) and protein ( P < 0.001) content, decreased the milk urea content ( P < 0.001), and increased the milk fat content of short- and medium-chained FAs (< C16, P < 0.001), C18:0 ( P < 0.01) and C18:2 n-6 ( P < 0.001), decreased the content of C16:0 ( P < 0.05), C18:1 t11 ( P < 0.001) and C18:3 n-3 ( P < 0.001), and increased the n-6/ n-3 FA ratio ( P < 0.001). The effect of concentrate supplementation was not affected by silage type, except for milk protein content where the positive effect of supplementation was stronger on WC than on RC diets ( P < 0.05). This study illustrates that the white- and red clover-grass mixtures investigated were widely similar with regard to their effects on grassland yield, silage intake and milk production and milk constituents, except for a higher milk fat content of C18:3 n-3 and C18:2 n-6 and lower n-6/ n-3 FA ratio on red clover diets. Our findings also show that N conversion efficiency from feed to milk on pure forage diets is more sensitive to changes in dietary protein intake than silage diets containing cereal based concentrates.

Longitudinal Associations Between Dietary Protein Intake and Survival in Hemodialysis Patients

Decreased dietary protein intake may be associated with increased mortality risk in individuals with kidney failure undergoing maintenance hemodialysis (MHD). We hypothesized that longitudinal changes in dietary protein intake have independent associations with survival in MHD patients. The relation between urea kinetic-based normalized protein nitrogen appearance (nPNA) and all-cause and cardiovascular mortality was examined in a 2-year (July 2001 to June 2003) cohort of 53,933 MHD patients from virtually all DaVita dialysis clinics in the United States, using both conventional and time-dependent (repeated-measure) Cox models to estimate death hazard ratios for quarterly averaged nPNA categories controlled for case-mix, comorbidity, dialysis dose (Kt/V), and available markers of malnutrition-inflammation complex syndrome (MICS). The best survival was associated with nPNA between 1.0 and 1.4 g/kg/d, whereas nPNA less than 0.8 or greater than 1.4 g/kg/d was associated with greater mortality in almost all models. Adjustment for MICS mitigated the associations substantially. A decrease in protein intake during the first 6 months in patients with an nPNA in the 0.8- to 1.2-g/kg/d range was associated incrementally with greater death risks in the subsequent 18 months, whereas an increase in nPNA tended to correlate with reduced death risk. Low daily protein intake or decrease in its magnitude over time is associated with increased risk for death in MHD patients. Whether the association between time-varying protein intake and survival is causal or a consequence of anorexia secondary to MICS or other factors needs to be explored further in interventional trials.

Cerebrospinal fluid concentrations of tryptophan and 5-hydroxyindoleacetic acid in Macaca mulatta: diurnal variations and response to chronic changes in dietary protein intake.

In rats, dietary protein is known to influence brain tryptophan (TRP) concentrations and serotonin (5HT) synthesis. However, few studies have examined this relationship in primates (including humans). We therefore studied the effect in monkeys of changes in chronic protein intake on plasma and cerebrospinal fluid (CSF) concentrations of TRP and 5-hydroxyindoleacetic acid (5HIAA), the principal 5HT metabolite. Juvenile male monkeys (Macacca mulatta) consumed for sequential 4-week periods diets differing in protein content (approximately 23%-->approximately 16%--> approximately 10%-->approximately 6% protein [%-energy/day]). Each day, food was presented as a morning meal of fruit, and an afternoon meal consisting of a pelleted, commercial diet and fruit. During week 4 on each diet, blood and CSF were sampled diurnally via indwelling catheters. Plasma and CSF TRP varied diurnally and with dietary protein content. On all diets, CSF TRP declined modestly in the morning, and increased in the afternoon; the magnitude of the increments varied directly with dietary protein content. Diurnal variations were absent for CSF 5HIAA; however, CSF 5HIAA varied directly with chronic dietary protein content. We conclude that dietary protein content can chronically influence CSF TRP concentrations in monkeys. The variation in CSF 5HIAA suggests chronic protein intake may influence serotonin synthesis and turnover, perhaps via changes in TRP concentrations.

Variations in Dietary Protein but Not in Dietary Fat Plus Cellulose or Carbohydrate Levels Affect Cysteine Metabolism in Rat Isolated Hepatocytes

To determine if previously observed effects of dietary protein on hepatic cysteine metabolism were due specifically to increases in dietary protein or to the accompanying decreases in dietary carbohydrate, two experiments were conducted. In one experiment, rats were fed diets that contained different levels of protein vs. an isocaloric mixture of fat + cellulose and a constant amount of carbohydrate. In the other, rats were fed diets that contained a constant amount of protein but different levels of carbohydrate vs. an isocaloric mixture of fat + cellulose. Diets were fed for 2–3 wk and hepatocytes were then isolated. Hepatic cysteine dioxygenase activity increased and cysteinesulfinate decarboxylase and γ-glutamylcysteine synthetase activities decreased in a stepwise manner when protein was added to the diet at the expense of fat + cellulose. Changes in cysteine dioxygenase, cysteinesulfinate decarboxylase and γ-glutamylcysteine synthetase activities were consistent with changes in rates of cysteine catabolism, taurine production and glutathione synthesis, respectively, by intact hepatocytes incubated with 0.2 mmol/L cysteine. When the carbohydrate to fat + cellulose ratio was varied, but the protein level was held constant, little or no change in enzyme activities or levels of metabolite production was observed. Regulation of the activities of enzymes involved in cysteine metabolism is predominantly due to changes in dietary protein intake and not to the associated changes in intake of other dietary macronutrients.

The Effect of Dietary Crude Protein as Protected Soybean Meal on Mammary Metabolism in the Lactating Dairy Cow

Metabolism in the mammary gland was related to changes in milk output in response to changes in dietary protein intake. Three diets of grass silage and concentrate were fed to four lactating dairy cows equipped with intravascular catheters across the mammary gland. Concentrates differed in the inclusion of protected soybean meal and provided 11.3, 15.4, and 20.1% CP, respectively. Blood samples were taken to assess the effect of protein percentage on the nutrient fluxes across the gland and their relationship to milk production. Milk production, milk protein yield, and milk protein concentration were all increased as CP intake increased, although these responses were not linear. Concentrations of urea in milk reflected those in plasma and increased as dietary protein intake increased. Uptake of glucose and BHBA by the mammary gland tended to increase as milk production increased. Arterial supply of essential AA increased as the dietary protein increased. Supply and uptake of nonessential AA were unchanged by dietary treatment, and uptake was insufficient to account for output of nonessential AA residues in milk protein. The supply of essential AA was not limiting for milk protein synthesis, and some alternative mechanism must have existed for the control of milk protein yield.

Changes in dietary protein intake fail to prevent decrease in muscle growth induced by severe hypoxia in rats

Muscle growth, fiber size, muscle and liver glycogen, plasma hormones, and muscle glutamine concentration were evaluated in rats chronically exposed (26 days) to a simulated hypobaric altitude (HA; 6,000 m) and fed diets of varying protein concentrations (10, 20, or 40 g protein/100 g of dry matter; LP, MP, and HP, respectively). Values were compared with those measured in animals maintained under normobaric conditions and either fed ad libitum (SL groups) or pair fed equivalent quantities of food consumed by HA animals (PF groups). There was marked anorexia in response to HA exposure for all protein diets (P < 0.001). A specific effect of hypoxia on the decrease in muscle growth has been identified by comparison of the values of the muscle weight-to-body weight ratio between HA and PF groups (P < 0.05 for all dietary protein levels). Plasma insulin concentrations were lower in HA than in SL and PF rats (P < 0.05). Liver glycogen was significantly decreased by exposure to HA (P < 0.001) and high dietary protein content (P < 0.005). Hypoxia per se and decreased food intake had additive effects on soleus muscle glycogen concentrations. An increase in muscle glutamine was observed in rats fed the LP diet in comparison with the MP diet, especially in SL and PF groups (P < 0.05). These results clearly demonstrate that 1) hypobaric hypoxia per se decreases growth rate in rats and 2) increasing the dietary protein intakes in rat had no effect on the depression of muscle growth related to high altitude but had deleterious effects on glycogen deposition in liver and fast muscle.

Albuminuria causes lysozymuria in rats with Heymann nephritis

To determine if changes in dietary protein intake alter renal excretion of small molecular weight proteins in passive Heymann nephritis, 21 rats with passive Heymann nephritis were fed 8.5% protein for 12 days after injection with antiserum. Dietary protein intake was then increased to 40% in 10 rats (LP-HP) while 11 rats remained on 8.5% protein (LP-LP). Lysozymuria (UlysV) increased from 66.5 +/- 31.0 mcg/day to 457.5 +/- 98.0 mcg/day (P less than 0.001) after five days in LP-HP, but was unchanged in LP-LP. Albuminuria (UalbV) increased only in LP-HP, from 168 +/- 23 mg/day to 447 +/- 45 mg/day (P less than 0.001). Urinary lysozyme excretion correlated with UalbV (r = 0.737, P less than 0.001), and changes in UlysV correlated with changes in UalbV (r = 0.657, P less than 0.01). To determine whether the increase in UlysV was the direct effect of the change in diet, enalapril 40 mg/kg/day was administered to prevent the increase in UalbV that occurs when these rats are fed a high protein diet. Twelve rats were fed 8.5% (LP) and 10 were fed 40% protein (HP) from the time of injection with antiserum. Six LP (LPE) and five HP (HPE) received enalapril. UlysV was 873 +/- 391 mcg/day in HP and nearly undetectable in the other three groups. UalbV was significantly greater in HP (368 +/- 60 mg/day) compared to the other three groups (114 +/- 16 in LP, 136 +/- 44 in HPE, 95 +/- 21 in LPE.(ABSTRACT TRUNCATED AT 250 WORDS)

Methionine Metabolism in Mammals: Concentration of Metabolites in Rat Tissues

We have evaluated factors which regulate the content of methionine, adenosylmethionine, adenosylhomocysteine, cystine, cysteine and acid-soluble thiols in rat tissues. In liver the concentration of methionine appears relatively insensitive to changes in dietary protein intake. In contrast the hepatic levels of adenosylmethionine, adenosylhomocysteine, cystine, cysteine and soluble thiols increased with augmented dietary protein. The ratio of adenosylmethionine:adenosylhomocysteine approximated 6.0 in livers, brains, kidneys and skeletal muscles from rats fed the stock diet. Independent variation in the concentrations of these two metabolites did occur. However, the ratios in livers of animals maintained on diets with varying casein content equaled or exceeded a value of 5.0. We conclude that the maintenance of the concentration of methionine is the primary result of the various homeostatic mechanisms. In addition, most previous reports have overestimated the tissue content of adenosylhomocysteine.methionine adenosylmethionine adenosylhomocysteine sulfur amino acids transmethylation transsulfuration