Arginine Supplementation Research Articles

Excessive Supplement of l-Arginine Induces Myopia via Orchestrating the MEK-ERK-NO Signaling Pathway.

Myopia can impact an individual's quality of life and induce multiple complications. In this study, we randomly divided guinea pigs into the normal control (NC) group, the lens-induced myopia (LIM) group, the normal control plus l-arginine injection (l-Arg) group, and the normal control plus saline injection (NaCl) group. The animals in each group received the relevant treatments. The results showed that myopia was deeper in the LIM and l-Arg groups compared with the NC and NaCl groups. Our experimental results suggest that the excessive supplement of l-Arg will induce myopia onset and a MEK-ERK cascade that stimulates the downstream nNOS-MMP2 and NRF2-KEAP1 signaling pathways, which is accompanied by inflammatory responses, fibrosis changes, and oxidative stress. After receiving excessive arginine supplements, the experimental individuals showed myopic shifts and a similar pathological state as the LIM group. In conclusion, the supplement of excessive arginine may be a danger factor for myopia onset.

Arginine enhances activity of anammox consortia and process stability with increased nitrogen loading

Cross-feeding based on amino acids metabolism is an important strategy by which anammox bacteria and the co-existing heterotrophs facilitate their own growth and survival. Arginine is one of the necessary amino acids required for bacterial protein biosynthesis but whether adding arginine could benefit growth of anammox bacteria remains unknown. In this study, arginine was supplemented at dose of 5 mg·L−1 to promote the nitrogen removal performance of anammox bioreactors under varied loading rates. The results showed that nitrogen removal efficiency increased by 10.2 % under higher loading rates. Arginine addition substantially simulated the secretion of extracellular proteins and polysaccharides within anammox consortia as a strategy against unfavorable conditions. Canditatus Kuenenia dominated the anammox consortia and their 16S rRNA abundance and anammox-related functional genes were significantly increased by up to 0.42 times and 5.81 times, respectively. The findings of this study provided a feasible strategy to improve the performance of anammox reactors with arginine supplementation.

Evaluation of the Dietary Arginine Supplementation on Yellow Catfish: From a Low-Temperature Farming Perspective

The yellow catfish is an economically significant freshwater fish with increasing importance in aquaculture. However, the low temperature environments prevalent in certain regions pose challenges to its growth, development, and overall health. This study aimed to explore the impact of dietary arginine (Arg) addition on the growth, digestive capacity, and intestinal antioxidant response in fish under low temperature acclimation (18 °C). Total 720 fish were randomly distributed into six groups, each containing 120 fish. Over the course of eight weeks, each group was fed with diets about varying Arg concentrations (1.79–3.26 g/kg). The results indicated that Arg supplementation resulted in an increase in specific growth rate (SGR), feed intake (FI), feed efficiency (FE), as well as pancreatic enzyme activities in both pancreas and intestine. Conversely, malondialdehyde (MDA) and protein carbonyl (PC) contents initially decreased but increased with higher Arg concentrations. Glutathione peroxidase 1a (GPX1a) showed a positive correlation with nuclear factor-erythroid 2-related factor-2 (Nrf2), showing its role in antioxidative capacity. Furthermore, this study revealed that Arg significantly enhanced the activities of anti-superoxide anion, anti-hydroxyl radical, and anti-oxidative enzymes, along with the relative mRNA abundance of Copper-Zinc superoxide dismutase (CuZnSOD), catalase, GPX1a, glutamate-cysteine ligase catalytic subunit (GCLC), and Nrf2 in the intestine. It was determined that yellow catfish weighing between 61.0 g and 89.0 g require an intake of 26.8 g of Arg per kilogram of diet based on polynomial regression analysis of specific growth rate (SGR), which is equivalent to 37.0 g of dietary protein, under sub-low temperature conditions of 18 °C.

Response to therapy of creatine transporter deficiency caused by a hypomorphic variant in SLC6A8

Cerebral creatine deficiency syndromes (CCDS) are rare inherited metabolic disorders caused by defective biosynthesis or transport of creatine. These conditions are characterized by reduced accumulation of creatine in the brain, mild to severe intellectual disability, global developmental delay, and speech-language disorders. The amount of brain creatine reduction needed to cause symptoms is not known. Here we report a new patient with creatine transporter deficiency (CTD) who presented at 15 months of age with seizures and global delays with no speech at 3 years of age. Brain MRI was normal, but brain MRS indicated creatine levels reduced to about 20 % of normal. He had normal levels of creatine and guanidinoacetate in plasma, but increased creatine/creatinine ratio in urine. DNA sequencing identified a hemizygous c.832C > T (p.Arg278Cys) variant in the creatine transporter gene SLC6A8. Fibroblasts from this patient had about 25 % of normal creatine transport activity, a value much higher than that measured in patients whose variants introduced premature stop codons in SLC6A8. The child was started on supplements of creatine, glycine, and arginine. His speech improved dramatically, and he had no more seizures, even during episodes of fever. Despite the clinical improvement, a repeat MRS demonstrated similar levels of brain creatine. This study suggests that a reduction in creatine transporter activity to 25 % or less is sufficient to cause symptoms of brain creatine deficiency and that functionally milder forms of CTD might respond to supplements aimed at replenishing brain creatine.

Increasing arginine supplementation alleviated heat stress and citrulline can effectively substitute arginine in broilers

Increasing arginine supplementation alleviated heat stress and citrulline can effectively substitute arginine in broilers

Attenuating susceptibility to ascites in cold-stressed broiler chickens fed canola meal-based diets by supplementing arginine or guanidinoacetic acid, either alone or in combination with phenylalanine.

The purpose of this study was to determine the effects of dietary supplementation of arginine (ARG) or guanidinoacetic acid (GAA), with or without phenylalanine (PHE), on the ascites susceptibility in the cold-stressed broilers fed canola meal (CM)-based diet. A total of 450 one-day-old male broiler chicks were randomly allocated to 30 floor pens with 6 replications for each of the 5 treatments. The dietary treatments were as follows: CM-based diet (control), CM-based diet+2.57g/kg ARG, CM-based diet+1.8g/kg GAA, CM-based diet+2.57g/kg ARG+1.5g/kg PHE and CM-based diet+1.8g/kg GAA+1.5g/kg PHE. The groups experienced cold stress induction starting at 32°C on day one, with gradual reductions to 15°C on days 21. The temperature was then held at 15°C for the remainder of the experiment. The supplements ARG+PHE and GAA+PHE resulted in improved feed conversion ratios (FCR) when compared to the control group. In comparison with the control group, supplementation of ARG and ARG+PHE decreased the ascites mortality by increasing the plasma nitric oxide level (NO), blood O2 partial pressure, blood O2 saturation (SO2), and decreasing the blood CO2 partial pressure (PCO2) and right ventricle to total ventricle (RV:TV) ratio. Supplementation of GAA and GAA+PHE also declined ascites mortality by reducing blood PCO2 while increasing blood SO2 and plasma NO levels. Although plasma corticosterone level and RV:TV ratio were similar between the GAA and control groups, adding GAA+PHE significantly reduced both compared to the control group. In summary, supplementing cold-stressed broiler chicken diets with 2.57g/kg ARG may alleviate hypertension. Additionally, 1.8g/kg GAA proves to be an effective substitute for dietary ARG in low-ARG diets, alleviating adverse effects from cold stress. Proper PHE formulation, at 1.5g/kg in this study, is crucial when using ARG and GAA supplements.

Arginine alleviates LPS-induced leukocytes inflammation and apoptosis via adjusted NODs signaling

Arginine plays a key role in regulating the immune function of fish. To evaluate the effect of arginine on the immune response of largemouth bass (Micropterus salmoides), the effects of arginine on cell viability, NADPH oxidase activity, respiratory burst activity, and NO production of leukocytes were analyzed both in vitro and in vivo. In this study, we found that arginine could promote the respiratory burst activity of leucocytes both in vivo and in vitro. By incubating leukocytes with the combination of LPS and arginine, we found that arginine supplementation inhibited the expression of inflammatory genes (tumor necrosis factor-alpha, tnfα; interleukin(il) 8 and il10) and apoptotic genes (caspase3, caspase8, and caspase9) induced by LPS, as well as promoted the arginine metabolism. Arginine supplementation significantly induced (cd4-like)cd4 gene expression after LPS challenge. Further studies showed that LPS could significantly increase nucleotide-binding oligomerization domain containing 1 (nod1) gene expression, but decreased the nod2 gene. The arginine supplementation increased nuclear factor kappa-B (NF-κB) protein level. In conclusion, arginine can alleviate LPS-induced inflammatory response and apoptosis as well as induce cd4 gene expression against LPS challenge via adjusting the expression of NODs signaling.

Productive and metabolomic consequences of arginine supplementation in sows during different gestation periods in two different seasons

BackgroundThe prolificacy of sows (litter size at birth) has markedly increased, leading to higher post-natal mortality. Heat stress can exacerbate this issue. Arginine plays an important role in several physiological pathways; its effect on gestating sows can depend on the period of supplementation. This study evaluated the effects of arginine supplementation on the productive performance and physiological status of sows during different gestation periods and seasons, using a multi-omics approach.MethodsA total of 320 sows were divided into 4 groups over 2 seasons (warm/cold); a control group (CO) received a standard diet (including 16.5 g/d of arginine) and 3 other groups received the standard diet supplemented with 21.8 g/d of arginine (38.3 g/d of arginine) either during the first 35 d (Early35), the last 45 d (Late45) or throughout the entire gestation period (COM). The colostrum was analyzed for nutritional composition, immunoglobulins and metabolomic profile. Urine and feces were analyzed on d 35 and 106 for the metabolomic and microbial profiles. Piglet body weight and mortality were recorded at birth, d 6, d 26, and on d 14 post-weaning.ResultsInteractions between arginine and season were never significant. The Early35 group had a lower percentage of stillborn (P < 0.001), mummified (P = 0.002) and low birthweight (LBW) piglets (P = 0.02) than the CO group. The Late45 group had a lower percentage of stillborn piglets (P = 0.029) and a higher percentage of high birthweight piglets (HBW; P < 0.001) than the CO group. The COM group had a higher percentage of LBW (P = 0.004) and crushed piglets (P < 0.001) than the CO group. Arginine supplementation modifies the metabolome characterization of colostrum, urine, and feces. Creatine and nitric oxide pathways, as well as metabolites related to microbial activity, were influenced in all matrices. A slight trend in the beta diversity index was observed in the microbiome profile on d 35 (P = 0.064).ConclusionsArginine supplementation during early gestation reduced the percentage of stillborn and LBW piglets, while in the last third of pregnancy, it favored the percentage of HBW pigs and reduced the percentage of stillbirths, showing that arginine plays a significant role in the physiology of pregnant sows.

The effect of supplemental arginine on the gut microbial homeostasis of broilers during sub-clinical necrotic enteritis challenge.

Necrotic enteritis (NE) is an enteric disease of poultry that alters the structure of the gut microbial community causing dysbiosis. This 28day experiment investigated the effects of 125% and 135% arginine diets on the gut microbial diversity and composition of broilers during a subclinical NE challenge. One hundred and twenty one-day-old chicks were randomly allocated to 4 treatments with six replicates each- Uninfected + Basal, NE + Basal, NE + Arg 125%, and NE + Arg 135% diet groups. NE was induced by inoculating 1 × 104E. maxima sporulated oocysts on day 14 and 1 × 108CFUC. perfringens on days 19, 20, and 21 of age. The NE challenge significantly decreased the number of observed amplicon sequence variants (p = 0.03), the abundance of the phylum Firmicutes (p < 0.01), and the species Mediterraneibacter cottocaccae (p = 0.01) in the ceca of birds on day 21. The NE challenge significantly increased the Bray-Curtis index (p < 0.01), and the abundance of the phylum Bacteroidota (p < 0.01), family Odoribacteraceae (p < 0.01), genus Odoribacter (p < 0.01), and species O. splanchnicus (p = 0.01) on day 21. During NE, the 125% arginine diet restored the abundance of the phylum Bacteroidota (p = 0.03), family Odoribacteraceae (p = 0.03) and Oscillospiraceae (p = 0.03), genus Odoribacter (p = 0.03), and species O. splanchnicus (p = 0.03) and M. cottocaccae (p < 0.01) on day 21. The 135% arginine diet effectively restored the loss in alpha diversity (p = 0.01) caused by NE, the abundance of the phylum Firmicutes (p = 0.01) and Bacteroidota (p < 0.01), family Oscillospiraceae (p = 0.03) and Odoribacteraceae (p < 0.01), genus Odoribacter (p < 0.01), and species O. splanchnicus (p < 0.01) and M. cottocaccae (p < 0.01) on day 21. On day 28, the treatments had a significant effect on the cecal propionate (p = 0.01), butyrate (p = 0.04), and total SCFA (p = 0.04) concentrations. In conclusion, the 125% and 135% arginine diets restored gut microbial composition during a subclinical NE challenge, but not the cecal SCFA profile. Hence, arginine in combination with other feed additives could be used in restoring gut microbial homeostasis during NE in poultry.

Effects of early-life amino acids supplementation on fish responses to a thermal challenge.

Nutritional programming is a promising concept for promoting metabolic adaptation of fish to challenging conditions, such as the increase in water temperature. The present work evaluates in ovo arginine or glutamine supplementation as enhancers of zebrafish metabolic or absorptive capacity, respectively, at optimum (28 ºC) and challenging temperatures (32 ºC) in the long-term. Growth performance, free amino acids profile, methylation index and the activity levels of digestive and intermediary metabolism enzymes were analysed to assess the metabolic plasticity induced by an early nutritional intervention. Temperature affected fish larvae growth performance. At the end of the experimental period 28 ºC-fish showed higher dry weight than 32 ºC-fish. The effects of the early supplementation were reflected in the larval free amino acids profile at the end of the experiment. Higher methylation potential was observed in the ARG-fish. In ovo amino acid supplementation modulated the metabolic response in zebrafish larvae, however, the magnitude of this effect differed according to the amino acid and the temperature. Overall, arginine supplementation enhanced carbohydrates metabolism at 32 ºC. In conclusion, the present work suggests that in ovo arginine supplementation may promote a better adaptive response to higher temperatures.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes with coexisting nemaline myopathy: a case report

BackgroundMitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes and nemaline myopathy are two rare genetic conditions. We report the first case reported in world literature with coexistence of both these rare disorders.Case presentationA 11-year-old previously healthy Sri Lankan male child, product of a nonconsanguineous marriage with normal development presented with acute onset short lasting recurring episodes of right-sided eye deviation with impaired consciousness. In between episodes he regained consciousness. Family history revealed a similar presentation in the mother at 36 years of age. Examination was significant for short stature and proximal upper and lower limb weakness. His plasma and cerebrospinal fluid lactate were elevated. Magnetic resonance imaging brain had evidence of an acute infarction in the right occipital territory. Sanger sequencing for common mitochondrial variants of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes confirmed this diagnosis. Whole exome sequencing revealed pathogenic compound heterozygous variants in NEB gene implicating in coexisting nemaline myopathy. Acute presentation was managed with supportive care, antiepileptics, and mitochondrial supplementation. Currently he is stable on daily supplementation of arginine and limb-strengthening physiotherapy. He is being monitored closely clinically and with serum lactate level.ConclusionGenetic diseases are rare. Coexistence of two genetic conditions is even rarer. Genetic confirmation of diagnosis is imperative for prediction of complications, accurate management, and genetic counseling.

Investigation in yeast of novel variants in mitochondrial aminoacyl-tRNA synthetases WARS2, NARS2, and RARS2 genes associated with mitochondrial diseases.

Aminoacyl-transfer RiboNucleic Acid synthetases (ARSs) are essential enzymes that catalyze the attachment of each amino acid to their cognate tRNAs. Mitochondrial ARSs (mtARSs), which ensure protein synthesis within the mitochondria, are encoded by nuclear genes and imported into the organelle after translation in the cytosol. The extensive use of next generation sequencing (NGS) has resulted in an increasing number of variants in mtARS genes being identified and associated with mitochondrial diseases. The similarities between yeast and human mitochondrial translation machineries make yeast a good model to quickly and efficiently evaluate the effect of variants in mtARS genes. Genetic screening of patients with a clinical suspicion of mitochondrial disorders through a customized gene panel of known disease-genes, including all genes encoding mtARSs, led to the identification of missense variants in WARS2, NARS2 and RARS2. Most of them were classified as Variant of Uncertain Significance. We exploited yeast models to assess the functional consequences of the variants found in these genes encoding mitochondrial tryptophanyl-tRNA, asparaginyl-tRNA, and arginyl-tRNA synthetases, respectively. Mitochondrial phenotypes such as oxidative growth, oxygen consumption rate, Cox2 steady-state level and mitochondrial protein synthesis were analyzed in yeast strains deleted in MSW1, SLM5, and MSR1 (the yeast orthologues of WARS2, NARS2 and RARS2, respectively), and expressing the wild type or the mutant alleles. Pathogenicity was confirmed for most variants, leading to their reclassification as Likely Pathogenic. Moreover, the beneficial effects observed after asparagine and arginine supplementation in the growth medium suggest them as a potential therapeutic approach.

L-Arginine supplementation for pregnant and lactating sows may improve the performance of piglets: A systematic review.

The objective was to conduct a systematic review to clarify the effects of l-arginine supplementation in pregnant and lactating sows on plasma hormone levels, milk production and composition, the body condition of sows and piglet performance. In April 2023, an online search and a systematic search were performed in the following databases: Embase, Scopus, SciELO, Web of Science, PubMed and Science Direct. The combinations of keywords used were sow and arginine and lactation; sow and arginine and lactating; sow and arginine and gestation; sow and arginine and gestating; sow and arginine and pregnancy; sow and arginine and reproduction; piglet and arginine; and sow and arginine and mammary gland. In total, 21 scientific articles with original data were selected according to preestablished criteria. Among the 21 articles, seven (33%) reported measurements of some plasma hormones, and among these, six reported an increase in the levels of at least one hormone, namely, estradiol, insulin-like growth factor 1 (IGF-1), insulin, follicle stimulating hormone, growth hormone or prolactin, with l-arginine supplementation. The parameters of milk were evaluated in 11 studies (52%), one reported an increase in protein content, and one reported an increase in IGF-1 content in milk with supplementation of this amino acid. Of the 14 studies that evaluated the performance parameters of piglets, only four reported improvements in some parameters of piglets from sows that received supplementation. Dietary supplementation of arginine for sows in the final third of gestation and/or lactation may alter the plasma levels of some hormones, which may reflect in greater development of the mammary gland tissue and, consequently, promote benefits on the performance of piglets. However, more studies are needed to evaluate the real impact of this amino acid supplementation on the physiology of the sows, in general, and the performance of suckling piglets.

Commensal Yeast Promotes Salmonella Typhimurium Virulence.

Enteric pathogens engage in complex interactions with the host and the resident microbiota to establish gut colonization. Although mechanistic interactions between enteric pathogens and bacterial commensals have been extensively studied, whether and how commensal fungi affect pathogenesis of enteric infections remains largely unknown. Here we show that colonization with the common human gut commensal fungus Candida albicans worsened infections with the enteric pathogen Salmonella enterica serovar Typhimurium. Presence of C. albicans in the mouse gut increased Salmonella cecum colonization and systemic dissemination. We investigated the underlying mechanism and found that Salmonella binds to C. albicans via Type 1 fimbriae and uses its Type 3 Secretion System (T3SS) to deliver effector proteins into C. albicans . A specific effector, SopB, was sufficient to manipulate C. albicans metabolism, triggering increased arginine biosynthesis in C. albicans and the release of millimolar amounts of arginine into the extracellular environment. The released arginine, in turn, induced T3SS expression in Salmonella , increasing its invasion of epithelial cells. C. albicans deficient in arginine production was unable to increase Salmonella virulence in vitro or in vivo . In addition to modulating pathogen invasion, arginine also directly influenced the host response to infection. Arginine-producing C. albicans dampened the inflammatory response during Salmonella infection, whereas C. albicans deficient in arginine production did not. Arginine supplementation in the absence of C. albicans increased the systemic spread of Salmonella and decreased the inflammatory response, phenocopying the presence of C. albicans . In summary, we identified C. albicans colonization as a susceptibility factor for disseminated Salmonella infection, and arginine as a central metabolite in the cross-kingdom interaction between fungi, bacteria, and host.

Impact of dietary arginine supplementation on immune responses and growth performance in Newcastle disease virus-infected broiler chicks.

Newcastle disease (ND) poses significant challenges within the poultry industry, leading to increased mortality rates, compromised growth, weakened immunity and elevated levels of inflammation. This study explores the potential of dietary arginine supplementation to ameliorate these adverse effects of ND, leveraging arginine's well-documented benefits in enhancing growth and immune responses. A total of 480 one-day-old male broiler chicks were meticulously categorised into eight groups, encompassing both infected and noninfected cohorts. These chicks received diets with arginine levels at 85%, 100%, 125% and 150% of recommended standards. The study entailed a comprehensive examination of clinical manifestations, growth performance metrics, haemagglutination inhibition (HI) test results, and serum concentrations of proinflammatory cytokines, adrenocorticotropic hormone (ACTH), and cortisol (CORT). The infection significantly curtailed feed consumption (p = 0.0001) and weight gain (p = 0.0001) while concurrently depressing HI titres. Additionally, infected chicks experienced an exacerbated feed conversion ratio (p = 0.0001), escalated mortality rates (p = 0.0001), and elevated serum concentrations of proinflammatory cytokines (p = 0.0001), ACTH (p = 0.0001), and CORT (p = 0.0001). Remarkably, dietary arginine supplementation effectively mitigated the adverse impacts of ND infection on growth, immune responses and proinflammatory cytokine levels. In the context of ND infection, mortality rates and inflammation surge, while growth and immunity are significantly compromised. The strategic inclusion of arginine in the diet emerges as a potent strategy to counteract the deleterious effects of ND. Supplementation with arginine at levels exceeding the conventional dietary recommendations is recommended to alleviate the detrimental consequences of ND effectively.

The effect of arginine on the growth of probiotics

Objective(s)The study objective was to examine the effect of arginine (Arg) supplementation on the growth of probiotics. MethodsLacticaseibacillus rhamnosus GG, Lactiplantibacillus plantarum, and Lactobacillus acidophilus were identified as potential probiotics. L. rhamnosus GG and L. plantarum were selected for further experimentation. The probiotics were co-treated with 0.9 % NaCl (negative control), 0.5 % Arg, and 1.0 % Arg in a 1:1 ratio for 24 h at 5 % CO2, 37 °C. The probiotics were tested for growth profiles, spectroscopic turbidity assay, metabolic assays (XTT and WST-8), live/dead cell assessment using confocal laser scanning microscopy (CLSM), and colony forming units (CFU). ResultsThe growth profiles of L. rhamnosus GG and L. plantarum were found to be similar, whereas L. acidophilus showed minimal or no transition from the initial lag phase. In the turbidity assay, the end-point absorbance for L. rhamnosus GG with 1.0 % Arg was significantly lower than 0.9 % NaCl and 0.5 % Arg (p < 0.05). For metabolic assays and CFU, increasing concentrations of Arg increased the viable cells for L. rhamnosus GG (p < 0.05), but decreased viability for L. plantarum (p < 0.05). Metabolic assays with dual-species bacterial suspensions indicated that Arg co-treatment inhibited viable proportions compared to control (p < 0.05). The dead cell proportion was significantly lower than live cell proportion for all tested interventions and probiotics (p < 0.05). ConclusionIncreasing concentrations of Arg promote the growth of L. rhamnosus GG, while conversely inhibiting the growth of L. plantarum. Therefore, the effect of prebiotic Arg on probiotics is concentration-dependent, leading to a selective promotion or inhibition of growth. Clinical significanceThe present study results show that Arg supplementation can selectively enhance the growth of L. rhamnosus GG while inhibit the growth of L. plantarum. This underscores the need to consider strain-specific responses in probiotic formulations when developing Arg-based synbiotics for modulating biofilms and creating ecologically homeostatic biofilm microenvironments.

Arginine Promoted Ovarian Development in Pacific White Shrimp Litopenaeus vannamei via the NO-sGC-cGMP and TORC1 Signaling Pathways.

This study aimed to evaluate the effects of arginine (0.5%, 1%, 1.5%, 2%, and 2.5% arginine supplementation levels were selected) on the ovarian development of Pacific white shrimp (Litopenaeus vannamei). The analyzed arginine supplementation levels in each diet were 2.90%, 3.58%, 4.08%, 4.53%, 5.04%, and 5.55%, respectively. A total of 540 shrimp (an initial weight of approximately 14 g) with good vitality were randomly distributed into six treatments, each of which had three tanks (300 L in volume filled with 200 L of water), with 30 shrimp per duplicate. Shrimp were fed three times a day (6:00 a.m., 11:00 a.m., and 6:00 p.m.). The results showed that after the 12-week raring cycle, shrimp fed with 4.08% and 4.53% Arg achieved better ovary development, which was identified by ovarian stage statistics, ovarian morphology observation, serum hormone levels (methylfarneside (MF); 5-hydroxytryptamine (5-HT); estradiol (E2); and gonadotropin-releasing hormone (GnRH)), gene expression (DNA meiotic recombinase 1 (dmc1), proliferating cell nuclear antigen (pcna), drosophila steroid hormone 1 (cyp18a), retinoid X receptor (rxra), and ecdysone receptor (ecr)). Further in-depth analysis showed that 4.08% and 4.53% Arg supplementation increased the concentration of vitellogenin in hepatopancreas and serum (p < 0.05) and upregulated the expression level of hepatopancreatic vg and vgr (p < 0.05), which promoted the synthesis of hepatopancreas exogenous vitellogenin and then transported it into the ovary through the vitellogenin receptor and further promoted ovarian maturation in L. vannamei. Meanwhile, compared with the control group, the expression level of vg in the ovary of the 4.53% Arg group was significantly upregulated (p < 0.05), which indicated endogenous vitellogenin synthesis in ovarian maturation in L. vannamei. Moreover, the expression of genes related to the mechanistic target of the rapamycin complex 1 (mTORC1) pathway and protein levels was regulated by dietary arginine supplementation levels. Arginine metabolism-related products, including nitric oxide synthase (NOS), nitric oxide (NO), and cyclic guanosine monophosphate (cGMP), were also affected. RNA interference was applied here to study the molecular regulation mechanism of arginine on ovarian development in L. vannamei. A green fluorescent protein (GFP)-derived double-stranded RNA (dsGFP) is currently commonly used as a control, while TOR-derived dsRNA (dsTOR) and NOS-derived dsRNA (dsNOS) were designed to build the TOR and NOS in vivo knockdown model. The results showed that the mTORC1 and NO-sGC-cGMP pathways were inhibited, while the vitellogenin receptor and vitellogenin gene expression levels were downregulated significantly in the hepatopancreas and ovary. Overall, dietary arginine supplementation could enhance endogenous and exogenous vitellogenin synthesis to promote ovary development in L. vannamei, and the appropriate dosages were 4.08% and 4.53%. The NO-sGC-cGMP and mTORC1 signaling pathways mediated arginine in the regulation of ovary development in L. vannamei.

Dietary Supplementation with Rumen-Protected Arginine or N-Carbamylglutamate Enhances Fetal Liver Development in Nutrient-Restricted Pregnant Hu Ewes.

This study was conducted in nutrient-restricted pregnant Hu ewes to determine whether rumen-protected arginine (RP-Arg) or N-carbamylglutamate (NCG) supplementation affects fetal liver growth and development. From 35 d to 110 d of gestation, 32 Hu ewes were randomly divided into four groups: a control group (100% of the National Research Council (NRC) requirements), a nutrient-restricted group (50% of the NRC requirements), and two treatment groups (ARG and NCG, 50% of the NRC requirements, supplemented with 20 g/day RP-Arg or 5 g/day NCG, respectively). Fetal body weights, fetal liver growth performance, the capability of antioxidation, and the expression of the mRNA and proteins of apoptosis-related genes in the fetal liver were determined and analyzed at 110 d of gestation. The dry matter, water, fat, protein, and ash components of the fetal livers in the RG group were found to be lower than in the CG group, and these components were significantly higher in the NCG group than in the RG group (p < 0.05). A decrease in DNA, RNA, and protein concentrations and contents, as well as in protein/DNA ratios, was observed in the RG group in comparison to the CG group (p < 0.05). Compared with the RG group, the NCG group had higher concentrations of DNA, RNA, and protein, as well as higher protein/DNA ratios (p < 0.05). The RG group had lower concentrations of cholinesterase, nitric oxide, nitric oxide synthase, superoxide dismutase, alanine aminotransferase, and total protein than the CG group (p < 0.05). The RG group had higher levels of glutathione peroxidase, maleic dialdehyde, and aspartate aminotransferase than the CG group (p < 0.05). In the RG group, the mRNA and protein expression of p53 and Bax was significantly increased (p < 0.05) compared with the CG group, and the gene expression of FasL and Bcl-2, the ratio of Bcl-2 to Bax, and the protein expression of Bcl-2 in the RG group were lower (p < 0.05) than in the CG group. It appears that RP-Arg and NCG supplementation during pregnancy could influence fetal liver growth and development. A nutrition-based therapeutic intervention to alleviate reduced fetal growth can be developed based on this study, which has demonstrated that maternal undernutrition during pregnancy induces the maldevelopment of the fetal liver.

Proteobacteria impair anti-tumor immunity in the omentum by consuming arginine

Gut microbiota influence anti-tumor immunity, often by producing immune-modulating metabolites. However, microbes consume a variety of metabolites that may also impact host immune responses. We show that tumors grow unchecked in the omenta of microbe-replete mice due to immunosuppressive Tregs. By contrast, omental tumors in germ-free, neomycin-treated mice or mice colonized with altered Schaedler's flora (ASF) are spontaneously eliminated by CD8+ Tcells. These mice lack Proteobacteria capable of arginine catabolism, causing increases in serum arginine that activate the mammalian target of the rapamycin (mTOR) pathway in Tregs to reduce their suppressive capacity. Transfer of the Proteobacteria, Escherichia coli (E.coli), but not a mutant unable to catabolize arginine, to ASF mice reduces arginine levels, restores Treg suppression, and prevents tumor clearance. Supplementary arginine similarly decreases Treg suppressive capacity, increases CD8+ Tcell effectiveness, and reduces tumor burden. Thus, microbial consumption of arginine alters anti-tumor immunity, offering potential therapeutic strategies for tumors in visceral adipose tissue.

Effects of dietary arginine supplementation on muscle structure, meat characteristics and lipid oxidation products in lambs and its potential mechanisms of action

This study aimed to assess the effect of dietary arginine supplementation on muscle structure and meat characteristics of lambs also considering lipid oxidation products and to contribute to reveal its mechanisms of action using tandem mass tagging (TMT) proteomics. Eighteen lambs were allocated to two dietary treatment groups: control diet or control diet with the addition of 1% L-arginine. The results revealed that dietary arginine supplementation increased muscle fibre diameter and cross-sectional area (P < 0.05), which was attributable to protein deposition, as evidenced by increased RNA content, RNA/DNA ratio, inhibition of apoptotic enzyme activity, and alterations in the IGF-1/Akt signaling pathway (P < 0.05). In addition, dietary arginine elevated pH24h, a* values, and IMF content, decreased shear force value and backfat thickness (P < 0.05), as well as decreased the formation of lipid oxidation products involved in meat flavor including hexanal, heptanal, octanal, nonanal and 1-octen-3-ol by increasing the antioxidant capacity of the muscle (P < 0.05). The proteomics results suggested that seven enrichment pathways may be potential mechanisms by which arginine affected the muscle structure and meat characteristics of lambs. In summary, arginine supplementation in lamb diets provides a safe and effective way to improve meat quality, and antioxidant capacity of muscle of lamb.