Feeding Of High Protein Diet Research Articles

Long Term High Protein Diet Feeding Alters the Microbiome and Increases Intestinal Permeability, Systemic Inflammation and Kidney Injury in Mice.

This study evaluates the effects of a chronic high protein diet (HPD) on kidney injury, intestinal permeability and gut microbiota perturbations in a mouse model. Mice are fed a diet containing either 20% or 52% energy from protein for 24 weeks; protein displaced an equivalent amount of wheat starch. The HPD does not alter glycemic control or body weight. The HPD induces kidney injury as evidenced by increase in albuminuria, urinary kidney injury molecule-1, blood urea nitrogen, urinary isoprostanes and renal cortical NF-κB p65 gene expression. HPD decreases intestinal occludin gene expression, increases plasma endotoxin and plasma monocyte chemoattractant protein-1, indicating intestinal leakiness and systemic inflammation. Cecal microbial analysis reveals that HPD feeding does not alter alpha diversity; however, it does alter beta diversity, indicating an altered microbial community structure with HPD feeding. Predicted metagenome pathway analysis demonstrates a reduction in branched-chain amino acid synthesis and an increase of the urea cycle with consumption of a HPD. These results demonstrate that long term HPD consumption in mice causes albuminuria, systemic inflammation, increase in gastrointestinal permeability and is associated with gut microbiome remodeling with an increase in the urea cycle pathway, which may contribute to renal injury.

高タンパク質摂取によるRat肝臓Aspartate Transaminaseの誘導 Aspartate Transaminaseタンパク質はrat肝臓細胞質の SDS-PAGEで確認できる

高タンパク質摂取によるRat肝臓Aspartate Transaminaseの誘導 Aspartate Transaminaseタンパク質はrat肝臓細胞質の SDS-PAGEで確認できる

Chronic kidney disease reduces muscle mitochondria and exercise endurance and its exacerbation by dietary protein through inactivation of pyruvate dehydrogenase

Chronic kidney disease impairs physical performance. Here the time course and mechanism of muscle insufficiency in renal failure and the influence of dietary protein were studied using 5/6 nephrectomized C57Bl/6 mice, focusing on muscle mass and mitochondria. A decrease in muscle mitochondria and running distance was found in young (16-20 weeks) 5/6 nephrectomized mice, despite the preservation of muscle volume and power. However, a decrease in muscle volume, associated with a reduction in muscle power, was found in aged (48-52 weeks) 5/6 nephrectomized mice. A high-protein diet feeding from 8 weeks increased muscle volume and power in the mice; but this further decreased running distance. Activation of pyruvate dehydrogenase by dichloroacetate effectively recovered running distance that was decreased by dietary protein. These findings indicate the mechanism of muscle insufficiency in renal failure and suggest that activation of muscle mitochondria would serve as a potential strategy for improving the physical performance of the patients with chronic kidney disease.

Low-Carbohydrate, High-Protein Diet Affects Rhythmic Expression of Gluconeogenic Regulatory and Circadian Clock Genes in Mouse Peripheral Tissues

Recent studies have demonstrated that metabolic changes in mammals induce feedback regulation of the circadian clock. The present study evaluates the effects of a low-carbohydrate high-protein diet (HPD) on circadian behavior and peripheral circadian clocks in mice. Circadian rhythms of locomotor activity and core body temperature remained normal in mice fed with the HPD diet (HPD mice), suggesting that it did not affect the central clock in the hypothalamus. Two weeks of HPD feeding induced mild hypoglycemia without affecting body weight, although these mice consumed more calories than mice fed with a normal diet (ND mice). Plasma insulin levels were increased during the inactive phase in HPD mice, but increased twice, beginning and end of the active phase, in ND mice. Expression levels of the key gluconeogenic regulatory genes PEPCK and G6Pase were significantly induced in the liver and kidneys of HPD mice. The HPD appeared to induce peroxisome proliferator-activated receptor α (PPARα) activation, since mRNA expression levels of PPARα and its typical target genes, such as PDK4 and Cyp4A10, were significantly increased in the liver and kidneys. Circadian mRNA expression of clock genes, such as BMAL1, Cry1, NPAS2, and Rev-erbα, but not Per2, was significantly phase-advanced, and mean expression levels of BMAL1 and Cry1 mRNAs were significantly elevated, in the liver and kidneys of HPD mice. These findings suggest that a HPD not only affects glucose homeostasis, but that it also advances the molecular circadian clock in peripheral tissues. (Author correspondence: k-ooishi@aist.go.jp)

Effect of Protein Supplementation on Growth Performance in Female Goats and Sheep under Grazing Condition

The experiment was conducted to determine the effect of protein supplementation on growt h performance in female goats and sheep. Ten does and six ewes aged about 15 months and weighing on average, 13.9 and 14.4 kg respectively were studied in this experiment. Animals were allocated to tw o feeding regimes (low protein (LP), 168g and high protein (HP), 208g per kg DM) in a randomized block design according to live weight. HP diet did not significantly (p>0.05) increase live weight gain (33.0 vs. 25.2 g/d) in goats. In contrast, sheep received the HP diet significantly (p<0.05, p<0.01) improved DM intake (509.0 vs. 425.9 g/d) and live weight gain (36.6 vs. 10.7 g/d) compared to those given the LP diet. These results indicate that supplementary feeding of high protein diet (208g CP per kg DM) significantly increased growth performance of sheep under grazing condition.

Clinical predictors of cognitive function change in schizophrenia

Serine dehydratase mRNA in the livers of rats maintained on laboratory chow (containing 22% protein) under a 12-h light (7:00-19:00)/12-h dark (19:00-7:00) cycle showed a daily oscillation that was maximal at 19:00 and minimal at 7:00 with an amplitude of more than 20-fold. The feeding of high-protein diets (60 and 91% casein) did not affect the oscillation phase. Virtually identical oscillatory phases for the mature serine dehydratase mRNA and its precursor RNAs, and the results of nuclear run-off transcription assays indicated that the oscillation was generated at the level of transcription. Similar oscillation patters were seen in adrenalectomized, starved, or diabetic rats. However, the mRNA oscillation was not precisely reflected in the oscillation of enzyme activity or enzyme protein in both the phase and the amplitude. Rats maintained on laboratory chow under constant light for 2 weeks still showed mRNA oscillation with a peak at 3:00, whereas rats exposed to constant light and fed between 7:00 and 9:00 exhibited an oscillation peak at 3:00-7:00. Under the conditions of a 12-h light/dark cycle and a 2-h restricted feeding between 7:00 and 9:00, a broad peak was seen at 23:00-3:00. These results indicate that the rhythmic expression of serine dehydratase gene is controlled by both meal-responsive and photoresponsive regulators.

Diurnal Variation of the Serine Dehydratase mRNA Level in Rat Liver

Serine dehydratase mRNA in the livers of rats maintained on laboratory chow (containing 22% protein) under a 12-h light (7:00-19:00)/12-h dark (19:00-7:00) cycle showed a daily oscillation that was maximal at 19:00 and minimal at 7:00 with an amplitude of more than 20-fold. The feeding of high-protein diets (60 and 91% casein) did not affect the oscillation phase. Virtually identical oscillatory phases for the mature serine dehydratase mRNA and its precursor RNAs, and the results of nuclear run-off transcription assays indicated that the oscillation was generated at the level of transcription. Similar oscillation patters were seen in adrenalectomized, starved, or diabetic rats. However, the mRNA oscillation was not precisely reflected in the oscillation of enzyme activity or enzyme protein in both the phase and the amplitude. Rats maintained on laboratory chow under constant light for 2 weeks still showed mRNA oscillation with a peak at 3:00, whereas rats exposed to constant light and fed between 7:00 and 9:00 exhibited an oscillation peak at 3:00-7:00. Under the conditions of a 12-h light/dark cycle and a 2-h restricted feeding between 7:00 and 9:00, a broad peak was seen at 23:00-3:00. These results indicate that the rhythmic expression of serine dehydratase gene is controlled by both meal-responsive and photoresponsive regulators.

Genetic control of serine dehydratase and phosphoenolpyruvate carboxykinase in mice.

Inbred strains of mice were found to differ with regard to their endogenous activities of the liver enzyme serine dehydratase (SD) and phosphoenolpyruvate carboxykinase (PEPCK). The strain distribution patterns for the activity of each enzyme were identical. On feeding of high-protein diets or on fasting, the activities of both enzymes were induced in a concordant fashion which suggested the control of both enzymes by a single gene. Genetic analysis established that the induction of both enzymes on feeding of high-protein diets was controlled by a single gene (Sdr-1), whereas the induction of SD, but not of PEPCK, in fasting was controlled by different single gene (Sdr-2). The lack of segregation of the backcross generations with respect to PEPCK activities obtained on fasting precluded the establishment of any association of the response of PEPCK to fasting with either the Sdr-1 or Sdr-2 locus. The strain of mice (BALB/cJ) that had the ability to maximally induce both gluconeogenic enzymes under both dietary treatments failed to survive a fast as long as those strains with less ability to induce. This suggests that the ability to induce key enzymes in gluconeogenesis when food is unavailable is of little consequence with regard to their ability to produce essential nutrients necessary for survival.

Study on tyrosine: 2-oxoglutarate aminotransferase activity in the liver of tumor-bearing and injured mice.

Elevation of the liver tyrosine: 2-oxoglutarate aminotransferase (EC 2. 6. 1. 5.) activity was observed in Ehrlich ascites tumor bearing mice and also in mice with nonspecific stimuli, such as talcum injection and high protein diet feeding. Regarding the intracellular distribution of the enzyme activity, a higher percentage was demonstrated in the supernatant fraction of mice with acute nonspecific stimuli than in that of the control mice but not in that of mice with tumor. In case of chronic nonspecific stimuli such as repeated talcum injections or feeding on high protein diet for a long term, however the intracellular distribution of enzyme activity resembled that of the control mice. These changes in enzyme activity and its intracellular distribution were found to be closely related to the adrenal steroid hormone.

Amino Acid Deficiencies and Reaction of Chicks to Salmonella gallinarum

the rate of mortality among chicks infected with Salmonella gallinarum (1). In the absence of the salmonellosis resistance factor (SRF), the feeding of high-protein diets resulted in greater mortality among S.-typhimurium-infected mice (2), but, in the presence of SRF, increasing protein levels increased survivorship of mice with this infection. Schaedler and Dubos (4) noted that increasing protein levels increased the survival time of mice subjected to various infections.

Recognition and treatment of alterations in ammonia metabolism.

As clinical and experimental knowledge of ammonia metabolism increases, the relationship between increased concentrations of ammonia in the blood and the clinical state of coma becomes apparent. The occurrence of significantly increased concentrations of ammonia in the blood of patients with coma and the clearing of the sensorium that follows a reduction of the blood ammonia concentration both indicate that ammonia intoxication is an important factor in the production of hepatic encephalopathies. Further confirmation of an etiologic role of ammonia in coma is to be found in the fact that this syndrome can be reproduced in both experimental animals and human subjects by increasing the blood ammonia, either by the administration of ammonium salts or by the feeding of high-protein diets or urea. In patients who have had vascular shunting procedures done for portal hypertension, or in patients in whom chronic liver disease is associated with gastrointestinal

THE DIET AND HORMONALLY INDUCED NEPHROSCLEROSIS

Kidney lesions resembling those of chronic nephritis and nephrosclerosis developed in rats treated with L.A.P. (lyophilized anterior pituitary) and fed 'Purina', but did not develop in similar rats similarly treated and fed Purina mixed with cornstarch in a 1: 1 ratio. When synthetic diets, differing only in their relative carbohydrate and protein content, were fed, only those L.A.P.-treated rats that consumed a regimen containing 30% casein and 54% cornstarch developed nephrosclerosis. No such lesions were seen in treated rats kept on a 15% casein and 69% cornstarch diet. This difference in response is due to the protein and not to the cornstarch content of these diets; the entire amount of cornstarch was substituted by wheat starch or 15% of it was replaced by an equicaloric amount of fat, without influencing the development of kidney lesions.Various protein preparations differed in their ability to cause kidney damage. Casein, egg albumen, and wheat gluten were more damaging than lactalbumin, gelatin, or zein.The severity of nephrosclerosis caused by L.A.P. roughly paralleled the kidney hypertrophy, adrenal enlargement, and increased appetite for water, but not necessarily the food intake or the growth rate. The appearance of these renal lesions was not associated with any gross change in urine pH, but was preceded by a marked albuminuria. By the fifth day, large amounts of albumin were present in the urine of the majority of treated rats consuming the 30% casein diet. Albumin rarely appeared in the urine of treated rats consuming the 15% casein diet.These findings were discussed in relation to the literature concerning the dietary production of chronic nephritis. The procedure described in this paper greatly accelerates the development of kidney lesions, apparently identical with those shown previously to ensue on the feeding of high protein diets.