glutaminase and Weight-Gain

The aim of the present study was to investigate the effects of the alanyl-glutamine dipeptide (Ala-Gln) or the combination supplementation of free alanine and glutamine (Ala+Gln) on the mammalian target of rapamycin (mTOR) and ubiquitin-proteasome proteolysis (UPP) signaling pathways in piglets.. We randomly allocated 180 piglets to three treatments with three replicates of 20 piglets each, fed with diets containing 0.62% Ala, 0.5% Ala-Gln, 0.21% Ala+0.34% Gln, respectively. The duration of the experiment was 28 d.. The results showed that Ala-Gln increased average daily gain of piglets, and decreased the ratio of feed to gain (P < 0.05). Ala-Gln supplementation increased the concentrations of Gln and glutamate and decreased the activity of glutamine synthetase in liver and skeletal muscle (P < 0.05). Ala-Gln increased the expression of glutaminase and glutamate dehydrogenate (P < 0.05). The increased phosphorylation of eIF-4 E binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1) in Ala-Gln treatment were associated with phosphorylation of the mTOR in liver and skeletal muscle. Ala+Gln did not affect the phosphorylation abundances of mTOR, 4E-BP1, or S6K1 (P > 0.05). Ala-Gln supplementation inhibited the mRNA expressions of MAFbx and MuRF1 in skeletal muscle of piglets (P < 0.05).. Taken together, Ala-Gln supplementation improved the growth performance of piglets, enhanced the metabolism of Gln, upregulated protein synthetic signaling in liver and skeletal muscle and decreased protein degradative signaling in muscle of piglets. Moreover, these effects of Ala-Gln were more effective than those of Ala+Gln.

Topics: Alanine; Alanine Transaminase; Animals; Aspartate Aminotransferases; Dietary Supplements; Dipeptides; Glutamate Dehydrogenase; Glutamate-Ammonia Ligase; Glutamic Acid; Glutaminase; Glutamine; Liver; Male; Muscle, Skeletal; Proteasome Endopeptidase Complex; Proteolysis; RNA, Messenger; Signal Transduction; Sus scrofa; TOR Serine-Threonine Kinases; Ubiquitins; Weight Gain

As a highly toxic environmental pollutant, methylmercury (MeHg) can cause neurotoxicity in animals and humans. Considering the antioxidant property of grape seed proanthocyanidin extracts (GSPE), this study was aimed to evaluate the effect of GSPE on MeHg-induced neurotoxicity in rats. Rats were exposed to MeHg by intraperitoneal injection (4, 12 μmol/kg, respectively) and GSPE was administered by gavage (250 mg/kg) 2 h later. After a 4-week treatment, phosphate-activated glutaminase, glutamine synthetase, glutathione peroxidase and superoxide dismutase activities, glutamate, glutamine, malondialdehyde and glutathione contents in cerebral cortex were measured. Reactive oxygen species (ROS) and apoptosis were also estimated in cells. The results showed that the MeHg-induced neurotoxicity was significantly attenuated. GSPE significantly decreased the production of ROS, counteracted oxidative damage and increased the antioxidants and antioxidant enzymes activities in rats prior to MeHg exposure. Moreover, the effects on the rate of apoptotic cells and the disturbance of glutamate homeostasis were correspondingly modulated. These observations highlighted the potential of GSPE in offering protection against MeHg-induced neurotoxicity.

Topics: Animals; Antioxidants; Apoptosis; Body Weight; Cells, Cultured; Cerebral Cortex; Flow Cytometry; Glutamate-Ammonia Ligase; Glutaminase; Glutathione; Glutathione Peroxidase; Grape Seed Extract; Injections, Intraperitoneal; Malondialdehyde; Methylmercury Compounds; Neurotoxicity Syndromes; Proanthocyanidins; Rats; Rats, Wistar; Reactive Oxygen Species; Superoxide Dismutase; Weight Gain

Several studies have shown impairment of neutrophil function, a disorder that contributes to the high incidence of infections in diabetes. Since glucose and glutamine play a key role in neutrophil function, we investigated their metabolism in neutrophils obtained from the peritoneal cavity of streptozotocin-induced diabetic rats. The activities of hexokinase, glucose-6-phosphate dehydrogenase (G6PDH), phosphofructokinase (PFK), citrate synthase, phosphate-dependent glutaminase, NAD+-linked and NADP+-linked isocitrate dehydrogenase were assayed. Glucose, glutamine, lactate, glutamate and aspartate, and the decarboxylation of [U-14C], [1-14C] and [6-14C]glucose; [U-14C]palmitic acid; and [U-14C]glutamine were measured in 1-h incubated neutrophils. Phagocytosis capacity and hydrogen peroxide (H2O2) production were also determined. All measurements were carried out in neutrophils from control, diabetic and insulin-treated (2-4 IU/day) diabetic rats. Phagocytosis and phorbol myristate acetate (PMA)-stimulated H2O2 production were decreased in neutrophils from diabetic rats. The activities of G6PDH and glutaminase were decreased, whereas that of PFK was raised by the diabetic state. The activities of the remaining enzymes were not changed. Diabetes decreased the decarboxylation of [1-14C]glucose and [U-14C]glutamine; however, [6-14C]glucose and [U-14C]palmitic acid decarboxylation was increased. These observations indicate that changes in metabolism may play an important role in the impaired neutrophil function observed in diabetes. The treatment with insulin abolished the changes induced by the diabetic state even with no marked change in glycemia. Therefore, insulin may have a direct effect on neutrophil metabolism and function.

Topics: Animals; Blood Glucose; Cells, Cultured; Citrate (si)-Synthase; Diabetes Mellitus, Experimental; Glucose; Glucosephosphate Dehydrogenase; Glutaminase; Glutamine; Hydrogen Peroxide; Hypoglycemic Agents; Insulin, Isophane; Isocitrate Dehydrogenase; Leukocyte Count; Male; Neutrophils; Palmitic Acid; Phagocytosis; Phosphofructokinases; Rats; Rats, Wistar; Weight Gain

After small bowel resection, parenteral nutrition is often required to provide energy and nitrogen supplies and also to stimulate intestinal adaptation, despite the absence of glutamine in formulas. The aim of this study was to investigate the effect of nutrient supply route on fuel utilization by enterocytes.. Rats received an intravenous or intragastric continuous infusion of an all-in-one glutamine-free formula. Sham-operated control rats were orally fed and received the same protein-caloric supplies as the other two groups. On day 7, the rats were killed in the fed state, blood samples were collected, and the jejunoileum was removed. Enterocytes were isolated. Aliquots of cell suspensions were incubated (30 minutes at 37 degrees C) in the presence of [14C]glucose and [14C]glutamine (2 mmol/L). Substrate utilization was determined by measuring metabolites and CO2 generated.. Intravenously fed rats showed mild hyperglycemia and marked hyperinsulinemia. Plasma glutamine levels were similar in the three groups. Intravenously fed rats showed a simultaneous increase in glutamine utilization and a decrease in glucose utilization compared with intragastrically fed and control rats, without parallel changes in glutaminase and hexokinase activities. The basolateral glucose transporter protein concentration was reduced in intravenously fed rat enterocytes.. The route of nutrient delivery influences fuel utilization by enterocytes.

Topics: Animals; Blood Glucose; Cell Separation; Energy Intake; Glucose; Glutaminase; Glutamine; Hormones; Ileum; Intestinal Mucosa; Jejunum; Male; Parenteral Nutrition; Rats; Rats, Wistar; Sucrase; Weight Gain

Hypocalciuria associated with a high phosphorus intake is known to be both a parathyroid hormone and non-parathyroid hormone dependent event. The present study was designed to define the role that ammoniagenesis may play in the non-parathyroid hormone dependent pathway.. Male rats, initially weighing 160 g, were fed a purified diet containing, in g/kg diet, a single level of protein (200) and variable inorganic phosphorus (1.8, 4.5, 9.0) for 20 days.. Food intake and body weight were similar for the three groups. Significant inverse correlations were found for both urinary calcium and phosphorus and for urinary ammonia nitrogen and calcium excretion (r = -0.62, p < 0.01). Urinary ammonia nitrogen excretion was highly correlated with both phosphorus intake (r = 0.89, p < 0.001) and urinary phosphorus (r = 0.88, p < 0.001). Urinary urea nitrogen tended to vary inversely with phosphorus intake. High dietary phosphorus decreased the activity of glutamine synthetase and increased the activity of glutaminase I in kidney.. Tying-up some of the hydrogen ions destined for excretion by phosphorus-stimulated ammoniagenesis could reduce the interfering effect of hydrogen ion on kidney calcium reabsorption and provide a mechanism to explain why phosphorus can have a direct positive impact upon tubular calcium reabsorption.

Topics: Ammonia; Animals; Calcium; Eating; Glutamate-Ammonia Ligase; Glutaminase; Kidney; Male; Nitrogen; Phosphorus; Rats; Rats, Sprague-Dawley; Urea; Weight Gain