Sexual dimorphism in glucose metabolism is shaped by androgen-driven gut microbiome.

Males are generally more susceptible to impaired glucose metabolism and type 2 diabetes (T2D) than females. However, the underlying mechanisms remain to be determined. Here, we revealed that gut microbiome depletion abolished sexual dimorphism in glucose metabolism. The transfer of male donor microbiota into antibiotics-treated female mice led the recipients to be more insulin resistant. Depleting androgen via castration changed the gut microbiome of male mice to be more similar to that of females and improved glucose metabolism, while reintroducing dihydrotestosterone (DHT) reversed these alterations. More importantly, the effects of androgen on glucose metabolism were largely abolished when the gut microbiome was depleted. Next, we demonstrated that androgen modulated circulating glutamine and glutamine/glutamate (Gln/Glu) ratio partially depending on the gut microbiome, and glutamine supplementation increases insulin sensitivity in vitro. Our study identifies the effects of androgen in deteriorating glucose homeostasis partially by modulating the gut microbiome and circulating glutamine and Gln/Glu ratio, thereby contributing to the difference in glucose metabolism between the two sexes.

Development and validation of a UPLC-MS/MS method for the simultaneous determination of gamma-aminobutyric acid and glutamic acid in human plasma.

Gamma-aminobutyric acid (GABA) and its precursor glutamic acid are important neurotransmitters. Both are also present in peripheral tissues and the circulation, where abnormal plasma concentrations have been linked to specific mental disorders. In addition to endogenous synthesis, GABA and glutamic acid can be obtained from dietary sources. An increasing number of studies suggest beneficial cardio-metabolic effects of GABA intake, and therefore GABA is being marketed as a food supplement. The need for further research into their health effects merits accurate and sensitive methods to analyze GABA and glutamic acid in plasma. To this end, an ultra-pressure liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantification of GABA and glutamic acid in human plasma. Samples were prepared by a protein precipitation step and subsequent solid phase extraction using acetonitrile. Chromatographic separation was achieved on an Acquity UPLC HSS reversed phase C18 column using gradient elution. Analytes were detected using electrospray ionization and selective reaction monitoring. Standard curve concentrations for GABA ranged from 3.4 to 2500 ng/mL and for glutamic acid from 30.9 ng/mL to 22,500 ng/mL. Within- and between-day accuracy and precision were <10% in quality control samples at low, medium and high concentrations for both GABA and glutamic acid. GABA and glutamic acid were found to be stable in plasma after freeze-thaw cycles and up to 12 months of storage. The validated method was applied to human plasma from 17 volunteers. The observed concentrations ranged between 11.5 and 20.0 ng/ml and 2269 and 7625 ng/ml for respectively GABA and glutamic acid. The reported method is well suited for the measurement of plasma GABA and glutamic acid in pre-clinical or clinical studies.

Substitution of high-dose sucrose with fructose in high-fat diets resulted in higher plasma concentrations of aspartic acid, cystine, glutamic acid, ornithine and phenylalanine, and higher urine concentrations of arginine and citrulline.

High fructose intake has been shown to increase circulating alanine transaminase in humans, which could reflect damage to the liver by fructose but could also be linked to higher level of transamination of amino acids in liver. Therefore, we hypothesized that a diet with high content of fructose would affect the amino acid composition in rat plasma and urine differently from a diet with high sucrose content. Because high intake of sucrose and fructose is often accompanied with high intake of saturated fat in the Western-style diet, we wanted to compare the effects of high fructose/sucrose in diets with normal or high content of coconut oil on individual free amino acids plasma and urine. Male Wistar rats were fed diets with normal (10 wt%) or high (40 wt%) content of sucrose or fructose, with normal or high fat content (7 or 22 wt%) and 20 wt% protein (casein). Rats fed high-fructose high-fat diet had higher plasma concentrations of aspartic acid, cystine, glutamic acid, ornithine, and phenylalanine and higher urine concentrations of arginine and citrulline when compared to rats fed high-sucrose high-fat diet. Substituting normal content of sucrose with fructose in the diets had little impact on amino acids in plasma and urine. Serum concentrations of alanine transaminase, aspartate transaminase, and creatinine, and urine cystatin C and T cell immunoglobulin mucin-1 concentrations were comparable between the groups and within normal ranges. To conclude, substituting high-dose sucrose with high-dose fructose in high-fat diets affected amino acid compositions in plasma and urine.

Leucine alone or in combination with glutamic acid, but not with arginine, increases biceps femoris muscle and alters muscle AA transport and concentrations in fattening pigs.

Forty-eight Duroc × Large White × Landrace pigs with an average initial body weight of 77.09 ± 1.37 kg were used to investigate the effects of combination of leucine (Leu) with arginine (Arg) or glutamic acid (Glu) on muscle growth, free amino acid profiles, expression levels of amino acid transporters and growth-related genes in skeletal muscle. The animals were randomly assigned to one of the four treatment groups (12 pigs/group, castrated male:female = 1:1). The pigs in the control group were fed a basal diet (13% Crude Protein), and those in the experimental groups were fed the basal diet supplemented with 1.00% Leu (L group), 1.00% Leu + 1.00% Arg (LA group) or 1.00% Leu + 1.00% Glu (LG group). The experiment lasted for 60 days. Results showed an increase (p < 0.05) in biceps femoris (BF) muscle weight in the L group and LG group relative to the basal diet group. In longissimus dorsi (LD) muscle, Lys, taurine and total essential amino acid concentration increased in the LG group relative to the basal diet group (p < 0.05). In LG group, Glu and carnosine concentrations increased (p < 0.05) in the BF muscle, when compared to the basal diet group. The Leu and Lys concentrations of BF muscle were lower in the LA group than that in the L group (p < 0.05). A positive association was found between BF muscle weight and Leu concentration (p < 0.05). The LG group presented higher (p < 0.05) mRNA levels of ASCT2, LAT1, PAT2, SANT2 and TAT1 in LD muscle than those in the basal diet group. The mRNA levels of PAT2 and MyoD in BF muscle were upregulated (p < 0.05) in the LG group, compared with those in the basal diet group. In conclusion, Leu alone or in combination with Glu is benefit for biceps femoris muscle growth in fattening pig.

The plasma glutamate concentration as a complementary tool to differentiate benign PET-positive lung lesions from lung cancer.

BACKGROUND: Pulmonary imaging often identifies suspicious abnormalities resulting in supplementary diagnostic procedures. This study aims to investigate whether the metabolic fingerprint of plasma allows to discriminate between patients with lung inflammation and patients with lung cancer. METHODS: Metabolic profiles of plasma from 347 controls, 269 cancer patients and 108 patients with inflammation were obtained by 1H-NMR spectroscopy. Models to discriminate between groups were trained by PLS-LDA. A test set was used for independent validation. A ROC curve was built to evaluate the diagnostic performance of potential biomarkers. RESULTS: Sensitivity, specificity, PPV and NPV of PET-CT to diagnose cancer are 96, 23, 76 and 71%. Metabolic profiles differentiate between cancer and inflammation with a sensitivity of 89%, a specificity of 87% and a MCE of 12%. Removal of the glutamate metabolite results in an increase of MCE (38%) and a decrease of both sensitivity and specificity (62%), demonstrating the importance of glutamate for discrimination. At the cut-off point 0.31 on the ROC curve, the relative glutamate concentration discriminates between cancer and inflammation with a sensitivity of 85%, a specificity of 81%, and an AUC of 0.88. PPV and NPV are 92 and 69%. In PET-positive patients with a relative glutamate level ≤ 0.31 the sensitivity to diagnose cancer reaches 100% with a PPV of 94%. In PET-negative patients, a relative glutamate level > 0.31 increases the specificity of PET from 23% to 58% and results in a high NPV of 100%. In case of discrepancy between SUVmax and the glutamate concentration, lung cancer is missed in 19% of the cases. CONCLUSION: This study indicates that the 1H-NMR-derived relative plasma concentration of glutamate allows discrimination between lung cancer and lung inflammation. A glutamate level ≤ 0.31 in PET-positive patients corresponds to the diagnosis of lung cancer with a higher specificity and PPV than PET-CT. Glutamate levels > 0.31 in patients with PET negative lung lesions is likely to correspond with inflammation. Caution is needed for patients with conflicting SUVmax values and glutamate concentrations. Confirmation is needed in a prospective study with external validation and by another analytical technique such as HPLC-MS.

Exploration of the Relationship between Intestinal Colostrum or Milk, and Serum Metabolites in Neonatal Calves by Metabolomics Analysis.

In contrast to colostral immunoglobulins, changes in metabolite composition of ingested colostrum in the gut have received little attention. Here, we characterized the metabolite profiles of colostrum and milk, ingested colostrum and milk, and serum of neonatal calves by liquid chromatography tandem-mass spectrometry and gas chromatography-mass spectrometry metabolomics approaches. Colostrum and milk underwent similar changes in metabolite profiles in the gut after being ingested. These changes were characterized by increases in methionine, glutamate, thymine, and phosphorylcholine. After ingestion, colostrum concentrations of several metabolites, such as γ-aminobutyric acid, glutamate, cinnamic acid, and thymine increased, whereas concentrations of d-ribose, and arginine decreased. These increases and decreases occurred in a time-dependent manner and were associated with alanine, aspartate, glutamate, and pyrimidine metabolism, and valine, leucine, and isoleucine biosynthesis, respectively. Meanwhile, similar changes in serum metabolites were also observed in neonatal calves fed colostrum, which implies that colostrum metabolites are transported across the small intestine and into the bloodstream. In addition, several metabolites of ingested milk were detected in the gut, and were also transferred to the bloodstream. These metabolites were related to phenylalanine, tyrosine, tryptophan, valine, leucine, and isoleucine biosynthesis, the citrate cycle, and histidine metabolism. These findings reveal that the serum metabolome of neonatal calves' changes as a result of ingesting colostrum, which can provide health-related benefits in early life.

The Effect of Cisplatin on Blood Ammonia Elevation by Alanyl-Glutamine Supplementation.

BACKGROUND: Although there are many clinical studies in which the beneficial effect of glutamine formulation on mucositis induced by chemo/radiotherapy was evaluated, the results are sometimes conflicting with the report of clinical deterioration. Then, we hypothesized that chemotherapy may increase the incidence of hyperammonemia without comparable change of major parameters of hepatic/renal disorder. METHODS: To verify our hypothesis, we examined the increase in blood ammonia level with 1-h intravenous infusion of alanyl-glutamine on day 1-4 after cisplatin (CDDP) administration in rats and assessed the correlation with hepatic/renal parameters. RESULTS: Hepatic parameters (glutamate-oxaloacetic transaminase [GOT] and glutamic-pyruvic transaminase [GPT]) with CDDP did not change until day 3 and only GOT increased on day 4. Renal parameters (plasma creatinine, blood urea nitrogen) with CDDP continuously increased up to day 4. Alanyl-glutamine infusion significantly elevated blood ammonia level of CDDP rats with the peak on day 3, although the same dose did not change that of control rats. CONCLUSION: These results indicates that CDDP enhances the increase in blood ammonia level by glutamine supplementation without correlating with primary parameters for hepatic/renal dysfunction.

Exploring pathogenesis in subjects with subjective Tinnitus having kidney deficiency pattern in terms of Traditional Chinese Medicine based on serum metabolic profiles.

OBJECTIVE: To investigate the metabolic pathogenesis in subjects with subjective tinnitus (ST) having kidney deficiency pattern (KDP) (ST/KDP) in terms of Traditional Chinese Medicine. METHODS: Three groups of subjects, including healthy individuals, subjects with ST/KDP, and subjects who were healthy initially and then developed ST/KDP one year later (healthy ¡ú ST/KDP), were recruited for this study. Serum metabolic profiles of all subjects were analyzed using ultra-performance liquid chromatography coupled with quadruple-time-of-flight mass spectrometry. The metabolic characteristics of the ST/KDP subjects were determined, and the corresponding biomarkers were predicted. The metabolomics data from the healthy ¡ú ST/KDP subjects were collected for further verification. RESULTS: Twelve metabolites in the ST/KDP subjects were different from those of the healthy control subjects. Of these metabolites, according to the prediction, except for octanoic acid, other metabolites might characterize ST/KDP. Ten metabolites at the outcome ST/KDP stage were different from those at the initial (control) stage. Through the comparison of these metabolites with the predicted metabolites, five common metabolites, including upregulated glutamate, serotonin, orotic acid and 8-oxoguanine, as well as downregulated taurine, were found. These common metabolites were significantly associated with canonical pathways including calcium signaling, ¦Ã-aminobutyric acid (GABA) receptor signaling, purine and pyrimidine biosynthesis, taurine biosynthesis, and serotonin receptor signaling. CONCLUSION: The metabolic pathogenesis in ST/KDP subjects was characterized by upregulated glutamate, serotonin, orotic acid and 8-oxoguanine, as well as downregulated taurine, additionally, perturbations of calcium signaling, GABA receptor signaling, purine and pyrimidine biosynthesis, taurine biosynthesis, and serotonin receptor signaling.

Naringin regulates glutamate-nitric oxide cGMP pathway in ammonium chloride induced neurotoxicity.

Naringin, plant bioflavonoid extracted mainly from grapefruit and other related citrus species. This study was designed to assess the neuroprotective effect of naringin on ammonium chloride (NH4Cl) induced hyperammonemic rats. Experimental hyperammonemia was induced by intraperitonial injection (i.p) of NH4Cl (100mg/kg body weight (b.w.)) thrice a week for 8 consecutive weeks. Hyperammonemic rats were treated with naringin (80mg/kg b.w.) via oral gavage. Naringin administration drastically restored the levels of blood ammonia, plasma urea, nitric oxide (NO), glutamate, glutamine, lipid peroxidation, lipid profile, activities of liver marker enzymes, antioxidant status and sodium/potassium-ATPase (Na+/K+-ATPase). In addition, naringin supplementation reverted back the pathological changes of liver, brain and kidney tissues, the expressions of Glutamine synthetase (GS), Na+/K+-ATPase, neuronal nitric oxide (nNOS) and soluble guanylate cyclase (sGC) in hyperammonemic rats. Hence, this study suggested that nargingin exhibited their protective effect against NH4Cl induced toxicity via enhancing the activities of antioxidant enzymes and inhibiting the lipid peroxidation process. Take together, this study provides data that naingin effectively reduced neurotoxicity by attenuating hyperammonemia, suggesting that naringin act as a potential therapeutic agent to treat hyperammonemic rats.

Dietary supplementation with glutamine and γ-aminobutyric acid improves growth performance and serum parameters in 22- to 35-day-old broilers exposed to hot environment.

This study was designed using 360 21-day-old chicks to determine the influences of diet supplementation with glutamine (5 g/kg), γ-aminobutyric acid (GABA, 100 mg/kg) or their combinations on performance and serum parameters exposed to cycling high temperatures. From 22 to 35 days, the experimental groups (2 × 2) were subjected to circular heat stress by exposing them to 30-34 °C cycling, while the positive control group was exposed to 23 °C constant. The blood of broilers was collected to detect serum parameters on days 28 and 35. Compared with the positive control group, the cycling high temperature decreased (p < 0.05) the feed consumption, weight gain and serum total protein (TP), glucose, thyroxine (T4), insulin, alkaline phosphatase (ALP), glutamine, GABA and glutamate levels, while increased (p < 0.05) the serum triglyceride (TG), corticosterone (CS), glucagon (GN), creatine kinase (CK), glutamic oxaloacetic transaminase (GOT), nitric oxide synthase (NOS), glutamate pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) levels during 22-35 days. However, dietary glutamine (5 g/kg) increased (p < 0.05) the feed consumption, weight gain and serum levels of glutamine, TP, insulin and ALP, but decreased (p < 0.05) the serum TG, CK, GOT, NOS and GPT levels. Diet supplemented with GABA also increased (p < 0.05) weight gain and the serum levels of TP, T4, ALP, GABA and glutamine. In addition, the significant interactions (p < 0.05) between glutamine and GABA were found in the feed consumption, weight gain and the serum ALP, CK, LDH, GABA, T3 and T4 levels of heat-stressed chickens. This research indicated that dietary glutamine and GABA improved the antistress ability in performance and serum parameters of broilers under hot environment.

Metabolomic profiles illuminate the efficacy of Chinese herbal Da-Cheng-Qi decoction on acute pancreatitis in rats.

BACKGROUND AND OBJECTIVES: Chinese herbal drug Da-Cheng-Qi decoction (DCQD) has been widely used for decades to treat acute pancreatitis (AP). Previous trials are mostly designed to state the potential mechanisms of the therapeutic effects rather than to detect its whole effect on metabolism. This study aimed to investigate the efficacy of DCQD on metabolism in AP. METHODS: Twenty-two male adult Sprague-Dawley rats were randomized into three groups. AP was induced by retrograde ductal infusion of 3.5% sodium taurocholate solution in DCQD and AP group, while 0.9% saline solution was used in sham operation (SO) group. Blood samples were obtained 12 h after drug administration and a 600 MHz superconducting Nuclear Magnetic Resonance (NMR) spectrometer was used to detected plasma metabolites. Principal Components Analysis (PCA) and Partial Least Squares-Discriminant Analysis after Orthogonal Signal Correction (OSC-PLS-DA) were applied to analyze the Longitudinal Eddy-delay (LED) and Carr-Purcell-Meiboom-Gill (CPMG) spectra. RESULTS: Differences in concentrations of metabolites among the three groups were detected by OSC-PLS-DA of 1HNMR spectra (both LED and CPMG). Compared with SO group, DCQD group had higher levels of plasma glycerol, glutamic acid, low density lipoprotein (LDL), saturated fatty acid (FA) and lower levels of alanine and glutamine, while the metabolic changes were reversed in the AP group. CONCLUSIONS: Our results demonstrated that DCQD was capable of altering the changed concentrations of metabolites in rats with AP and 1HNMR-based metabolomic approach provided a new methodological cue for systematically investigating the efficacies and mechanisms of DCQD in treating AP.

Prolonged continuous intravenous infusion of the dipeptide L-alanine- L-glutamine significantly increases plasma glutamine and alanine without elevating brain glutamate in patients with severe traumatic brain injury.

INTRODUCTION: Low plasma glutamine levels are associated with worse clinical outcome. Intravenous glutamine infusion dose- dependently increases plasma glutamine levels, thereby correcting hypoglutaminemia. Glutamine may be transformed to glutamate which might limit its application at a higher dose in patients with severe traumatic brain injury (TBI). To date, the optimal glutamine dose required to normalize plasma glutamine levels without increasing plasma and cerebral glutamate has not yet been defined. METHODS: Changes in plasma and cerebral glutamine, alanine, and glutamate as well as indirect signs of metabolic impairment reflected by increased intracranial pressure (ICP), lactate, lactate-to-pyruvate ratio, electroencephalogram (EEG) activity were determined before, during, and after continuous intravenous infusion of 0.75 g L-alanine-L-glutamine which was given either for 24 hours (group 1, n = 6) or 5 days (group 2, n = 6) in addition to regular enteral nutrition. Lab values including nitrogen balance, urea and ammonia were determined daily. RESULTS: Continuous L-alanine-L-glutamine infusion significantly increased plasma and cerebral glutamine as well as alanine levels, being mostly sustained during the 5 day infusion phase (plasma glutamine: from 295 ± 62 to 500 ± 145 µmol/ l; brain glutamine: from 183 ± 188 to 549 ± 120 µmol/ l; plasma alanine: from 327 ± 91 to 622 ± 182 µmol/ l; brain alanine: from 48 ± 55 to 89 ± 129 µmol/ l; p < 0.05, ANOVA, post hoc Dunn's test). CONCLUSIONS: High dose L-alanine-L-glutamine infusion (0.75 g/ kg/ d up to 5 days) increased plasma and brain glutamine and alanine levels. This was not associated with elevated glutamate or signs of potential glutamate-mediated cerebral injury. The increased nitrogen load should be considered in patients with renal and hepatic dysfunction. TRIAL REGISTRATION: Clinicaltrials.gov NCT02130674. Registered 5 April 2014.

Effect of diet on brain metabolites and behavior in spontaneously hypertensive rats.

Attention-deficit hyperactivity disorder (ADHD) is a heterogeneous psychiatric disorder affecting 5-10% of children. One of the suggested mechanisms underlying the pathophysiology of ADHD is insufficient energy supply to neurons. Here, we investigated the role of omega 3 fatty acids in altering neural energy metabolism and behavior of spontaneously hypertensive rats (SHR), which is an animal model of ADHD. To this end, we employed Proton Magnetic Resonance Spectroscopy ((1)H MRS) to evaluate changes in brain neurochemistry in the SHR following consumption of one of three experimental diets (starting PND 21): fish oil enriched (FOE), regular (RD) and animal fat enriched (AFE) diet. Behavioral tests were performed to evaluate differences in locomotor activity and risk-taking behavior (starting PND 44). Comparison of frontal lobe metabolites showed that increased amounts of omega 3 fatty acids decreased total Creatine levels (tCr), but did not change Glutamate (Glu), total N-Acetylaspartate (tNAA), Lactate (Lac), Choline (Cho) or Inositol (Ino) levels. Although behavior was not significantly affected by different diets, significant correlations were observed between brain metabolites and behavior in the open field and elevated plus maze. SHR with higher levels of brain tCr and Glu exhibited greater hyperactivity in a familiar environment. On the other hand, risk-taking exploration of the elevated plus maze's open arms correlated negatively with forebrain tNAA and Lac levels. These findings support the possible alteration in energy metabolites in ADHD, correlating with hyperactivity in the animal model. The data also suggest that omega 3 fatty acids alter brain energy and phospholipid metabolism.

Effects of taurine supplementation on hepatic markers of inflammation and lipid metabolism in mothers and offspring in the setting of maternal obesity.

Maternal obesity is associated with obesity and metabolic disorders in offspring. However, intervention strategies to reverse or ameliorate the effects of maternal obesity on offspring health are limited. Following maternal undernutrition, taurine supplementation can improve outcomes in offspring, possibly via effects on glucose homeostasis and insulin secretion. The effects of taurine in mediating inflammatory processes as a protective mechanism has not been investigated. Further, the efficacy of taurine supplementation in the setting of maternal obesity is not known. Using a model of maternal obesity, we examined the effects of maternal taurine supplementation on outcomes related to inflammation and lipid metabolism in mothers and neonates. Time-mated Wistar rats were randomised to either: 1) control : control diet during pregnancy and lactation (CON); 2) CON supplemented with 1.5% taurine in drinking water (CT); 3) maternal obesogenic diet (high fat, high fructose) during pregnancy and lactation (MO); or 4) MO supplemented with taurine (MOT). Maternal and neonatal weights, plasma cytokines and hepatic gene expression were analysed. A MO diet resulted in maternal hyperinsulinemia and hyperleptinemia and increased plasma glucose, glutamate and TNF-α concentrations. Taurine normalised maternal plasma TNF-α and glutamate concentrations in MOT animals. Both MO and MOT mothers displayed evidence of fatty liver accompanied by alterations in key markers of hepatic lipid metabolism. MO neonates displayed a pro-inflammatory hepatic profile which was partially rescued in MOT offspring. Conversely, a pro-inflammatory phenotype was observed in MOT mothers suggesting a possible maternal trade-off to protect the neonate. Despite protective effects of taurine in MOT offspring, neonatal mortality was increased in CT neonates, indicating possible adverse effects of taurine in the setting of normal pregnancy. These data suggest that maternal taurine supplementation may ameliorate the adverse effects observed in offspring following a maternal obesogenic diet but these effects are dependent upon prior maternal nutritional background.

Supplementing monosodium glutamate to partial enteral nutrition slows gastric emptying in preterm pigs(1-3).

Emerging evidence suggests that free glutamate may play a functional role in modulating gastroduodenal motor function. We hypothesized that supplementing monosodium glutamate (MSG) to partial enteral nutrition stimulates gastric emptying in preterm pigs. Ten-day-old preterm, parenterally fed pigs received partial enteral nutrition (25%) as milk-based formula supplemented with MSG at 0, 1.7, 3.0, and 4.3 times the basal protein-bound glutamate intake (468 mg·kg(-1)·d(-1)) from d 4 to 8 of life (n = 5-8). Whole-body respiratory calorimetry and (13)C-octanoic acid breath tests were performed on d 4, 6, and 8. Body weight gain, stomach and intestinal weights, and arterial plasma glutamate and glutamine concentrations were not different among the MSG groups. Arterial plasma glutamate concentrations were significantly higher at birth than after 8 d of partial enteral nutrition. Also at d 8, the significant portal-arterial concentration difference in plasma glutamate was substantial (∼500 µmol/L) among all treatment groups, suggesting that there was substantial net intestinal glutamate absorption in preterm pigs. MSG supplementation dose-dependently increased gastric emptying time and decreased breath (13)CO2 enrichments, (13)CO2 production, percentage of (13)CO2 recovery/h, and cumulative percentage recovery of (13)C-octanoic acid. Circulating glucagon-like peptide-2 (GLP-2) concentration was significantly increased by MSG but was not associated with an increase in intestinal mucosal growth. In contrast to our hypothesis, our results suggest that adding MSG to partial enteral nutrition slows the gastric emptying rate, which may be associated with an inhibitory effect of increased circulating GLP-2.

Dietary supplementation with monosodium glutamate is safe and improves growth performance in postweaning pigs.

Dietary intake of glutamate by postweaning pigs is markedly reduced due to low feed consumption. This study was conducted to determine the safety and efficacy of dietary supplementation with monosodium glutamate (MSG) in postweaning pigs. Piglets were weaned at 21 days of age to a corn and soybean meal-based diet supplemented with 0, 0.5, 1, 2, and 4 % MSG (n = 25/group). MSG was added to the basal diet at the expense of cornstarch. At 42 days of age (21 days after weaning), blood samples (10 mL) were obtained from the jugular vein of 25 pigs/group at 1 and 4 h after feeding for hematological and clinical chemistry tests; thereafter, pigs (n = 6/group) were euthanized to obtain tissues for histopathological examinations. Feed intake was not affected by dietary supplementation with 0-2 % MSG and was 15 % lower in pigs supplemented with 4 % MSG compared with the 0 % MSG group. Compared with the control, dietary supplementation with 1, 2 and 4 % MSG dose-dependently increased plasma concentrations of glutamate, glutamine, and other amino acids (including lysine, methionine, phenylalanine and leucine), daily weight gain, and feed efficiency in postweaning pigs. At day 7 postweaning, dietary supplementation with 1-4 % MSG also increased jejunal villus height, DNA content, and antioxidative capacity. The MSG supplementation dose-dependently reduced the incidence of diarrhea during the first week after weaning. All variables in standard hematology and clinical chemistry tests, as well as gross and microscopic structures, did not differ among the five groups of pigs. These results indicate that dietary supplementation with up to 4 % MSG is safe and improves growth performance in postweaning pigs.

[Comparative study on effects between electroacupuncture and acupuncture for spastic paralysis after stroke].

OBJECTIVE: To observe the differences of therapeutic effect of spastic paralysis after stroke between electroacupuncture and acupuncture and explore the mechanism. METHODS: Sixty-four cases were randomly divided into an electroacupuncture group (n = 33) and an acupuncture group (n = 31). Both groups were treated with Bobath facilitation techniques and medicine treatments. Quchi (LI 11), Hegu (LI 4), Yanglingquan (GB 34), Sanyinjiao (SP 6), et al. on the affected side were selected in each group. The needle was retained for 30 min, and the manipulation was applied for 1 min in the acupuncture group, and electroacupuncture was added in the electroacupuncture group. Stroke Impairment Assessment Set (SIAS) was adopted to assess the whole function status after sroke, and the contents of glutamate (Glu) and gamma-aminobutyric acid (GABA) in serum and clinical efficacy were observed in the two groups. RESULTS: The SIAS score increased after treatment as compared with that before treatment in either group (both P < 0.01), and the electroacupuncture group was superior to the acupuncture group (P < 0.01); the content of Glu in blood serum and ratio of Glu/GABA reduced, while the content of GABA in serum increased after treatment as compared with those before treatment in either group (all P < 0.01), but the improvement of above indices were much more apparently in the electroacupuncture group as compared with those in the acupuncture group (P < 0.01, P < 0.05); the total effective rate of 90.9% (30/33) in the electroacupuncture group was superior to that of 83.9% (26/31) in the acupuncture group (P < 0.05). CONCLUSION: Electroacupuncture can improve therapeutic effect of spastic paralysis after stroke, it's mechanism may be ralated to ajusting the contents of Glu and GABA in serum.

Decreased glutamate, glutamine and citrulline concentrations in plasma and muscle in endotoxemia cannot be reversed by glutamate or glutamine supplementation: a primary intestinal defect?

Endotoxemia affects intestinal physiology. A decrease of circulating citrulline concentration is considered as a reflection of the intestinal function. Citrulline can be produced in enterocytes notably from glutamate and glutamine. The aim of this work was to determine if glutamate, glutamine and citrulline concentrations in blood, intestine and muscle are decreased by endotoxemia, and if supplementation with glutamate or glutamine can restore normal concentrations. We induced endotoxemia in rats by an intraperitoneal injection of 0.3 mg kg(-1) lipopolysaccharide (LPS). This led to a rapid anorexia, negative nitrogen balance and a transient increase of the circulating level of IL-6 and TNF-α. When compared with the values measured in pair fed (PF) animals, almost all circulating amino acids (AA) including citrulline decreased, suggesting a decrease of intestinal function. However, at D2 after LPS injection, most circulating AA concentrations were closed to the values recorded in the PF group. At that time, among AA, only glutamate, glutamine and citrulline were decreased in gastrocnemius muscle without change in intestinal mucosa. A supplementation with 4% monosodium glutamate (MSG) or an isomolar amount of glutamine failed to restore glutamate, glutamine and citrulline concentrations in plasma and muscle. However, MSG supplementation led to an accumulation of glutamate in the intestinal mucosa. In conclusion, endotoxemia rapidly but transiently decreased the circulating concentrations of almost all AA and more durably of glutamate, glutamine and citrulline in muscle. Supplementation with glutamate or glutamine failed to restore glutamate, glutamine and citrulline concentrations in plasma and muscles. The implication of a loss of the intestinal capacity for AA absorption and/or metabolism in endotoxemia (as judged from decreased citrulline plasma concentration) for explaining such results are discussed.

Anti-fatigue effect of Renshen Yangrong decoction in mice.

OBJECTIVE: To explore the anti-fatigue effect of Renshen Yangrong Decoction (RYD): in mice. METHODS: One hundred Kunming mice were randomly divided into 5 groups with 20 mice in each: group. The negative control group was treated with distilled water, the positive control group was treated with Shiyiwei Shenqi Tablet (, 1.0 g/kg), the high-, medium- and low-dose RYD groups were treated with 42.0, 21.0 and 10.5 g/kg of RYD daily, respectively, by gastric infusion. At the end of the 7-day treatment, loaded swimming time, organ wet weight and coefficient, serum glucose, urea nitrogen, and hepatic glycogen levels were determined. The outcomes were compared among groups. RESULTS: As compared with the negative: control group, the loaded swimming time was significantly increased in the positive control group, specifically the medium- and high-dose RYD groups (P<0.01). In addition, the wet weights and coefficients of the spleen and thymus, and the serum glucose and hepatic glycogen contents were increased, whereas serum urea nitrogen level was significantly decreased in the positive control group and the high dose RYD group (P<0.05 or P<0.01). CONCLUSION: RYD showed an anti-fatigue effect in mice.

Metabolic changes during a field experiment in a world-class windsurfing athlete: a trial with multivariate analyses.

Physical exercise affects hematological equilibrium and metabolism. This study evaluated the biochemical and hematological responses of a male world-class athlete in sailing who is ranked among the top athletes on the official ISAF ranking list of windsurfing, class RS:X. The results describe the metabolic adaptations of this athlete in response to exercise in two training situations: the first when the athlete was using the usual training and dietary protocol, and the second following training and nutritional interventions based on a careful analysis of his diet and metabolic changes measured in a simulated competition. The intervention protocol for this study consisted of a 3-month facility-based program using neuromuscular training (NT), aerobic training (AT), and nutritional changes to promote anabolism and correct micronutrient malnutrition. Nutritional and training intervention produced an increase in the plasma availability of branched-chain amino acids (BCAAs), aromatic amino acids (AAAs), alanine, glutamate, and glutamine during exercise. Both training and nutritional interventions reduced ammonemia, uricemia, and uremia. In addition, we are able to correct a significant drop in potassium levels during races by correct supplementation. Due to the uniqueness of this experiment, these results may not apply to other windsurfers, but we nonetheless had the opportunity to characterize the metabolic adaptations of this athlete. We also proposed the importance of in-field metabolic analyses to the understanding, support, and training of world-class elite athletes.