Effects Of Guanidinoacetic Acid Supplementation Research Articles

Effects of guanidinoacetic acid supplementation on liver and breast muscle fat deposition, lipid levels, and lipid metabolism-related gene expression in ducks.

Exogenous supplementation of guanidinoacetic acid can mechanistically regulate the energy distribution in muscle cells. This study aimed to investigate the effects of guanidinoacetic acid supplementation on liver and breast muscle fat deposition, lipid levels, and lipid metabolism-related gene expression in ducks. We randomly divided 480 42 days-old female Jiaji ducks into four groups with six replicates and 20 ducks for each replicate. The control group was fed the basal diet, and the experimental groups were fed the basal diet with 400, 600, and 800 mg/kg (GA400, GA600, and GA800) guanidinoacetic acid, respectively. Compared with the control group, (1) the total cholesterol (p = 0.0262), triglycerides (p = 0.0357), malondialdehyde (p = 0.0452) contents were lower in GA400, GA600 and GA800 in the liver; (2) the total cholesterol (p = 0.0365), triglycerides (p = 0.0459), and malondialdehyde (p = 0.0326) contents in breast muscle were decreased in GA400, GA600 and GA800; (3) the high density lipoprotein (p = 0.0356) and apolipoprotein-A1 (p = 0.0125) contents were increased in GA600 in the liver; (4) the apolipoprotein-A1 contents (p = 0.0489) in breast muscle were higher in GA600 and GA800; (5) the lipoprotein lipase contents (p = 0.0325) in the liver were higher in GA600 and GA800; (6) the malate dehydrogenase contents (p = 0.0269) in breast muscle were lower in GA400, GA600, and GA800; (7) the insulin induced gene 1 (p = 0.0326), fatty acid transport protein 1 (p = 0.0412), and lipoprotein lipase (p = 0.0235) relative expression were higher in GA400, GA600, and GA800 in the liver; (8) the insulin induced gene 1 (p = 0.0269), fatty acid transport protein 1 (p = 0.0234), and lipoprotein lipase (p = 0.0425) relative expression were increased in GA400, GA600, and GA800 in breast muscle. In this study, the optimum dosage of 600 mg/kg guanidinoacetic acid improved the liver and breast muscle fat deposition, lipid levels, and lipid metabolism-related gene expression in ducks.

Effects of guanidinoacetic acid supplementation on growth performance, hypothalamus-pituitary-adrenal axis, and immunity of broilers challenged with chronic heat stress

Heat stress can cause systemic immune dysregulation and threaten the health of broilers. Guanidinoacetic acid (GAA) has been shown to be effective against heat stress, but whether it is beneficial for immunity is unclear. Therefore, the effects of dietary GAA supplementation on the immunity of chronic heat-stressed broilers were evaluated. A total of 192 Arbor Acres male broilers (28-day old) were randomly allocated to 4 treatments: the normal control group (NC, 22°C, ad libitum feeding), the heat stress group (HS, 32°C, ad libitum feeding), the pair-fed group (PF, kept at 22°C and received food equivalent to that consumed by the HS group on the previous day), and the GAA group (HG, 32°C, ad libitum feeding; basal diet supplemented with 0.6 g/kg GAA). Samples were collected on d 7 and 14 after treatment. Results showed that broilers exposed to heat stress exhibited a decrease (P < 0.05) in ADG, ADFI, thymus and bursa of Fabricius indexes, and an increase (P < 0.05) in feed conversion ratio and panting frequency, compared to the NC group. Levels of corticotropin-releasing factor, corticosterone (CORT), heat shock protein 70 (HSP70), IL-6, and TNF-α were elevated (P < 0.05) while lysozyme and IgG concentration was decreased (P < 0.05) in the HS group compared with the NC group after 7 d of heat exposure. The concentrations of IgG and IL-2 were decreased (P < 0.05) and CORT was increased (P < 0.05) in the HS group compared with the NC group after 14 d of heat exposure. Noticeably, GAA supplementation decreased the levels of CORT (P < 0.05) and increased the IL-2, IgG, and IgM concentrations (P < 0.05) compared with the HS group. In conclusion, chronic heat stress increased CORT release, damaged immune organs, and impaired the immunity of broilers. Dietary supplementation of 0.6 g/kg GAA can reduce the CORT level and improve the immune function of broilers under heat stress conditions.

Epigenetic reprogramming-induced guanidinoacetic acid synthesis promotes pancreatic cancer metastasis and transcription-activating histone modifications

BackgroundPancreatic ductal adenocarcinoma (PDAC) tends to undergo distant metastasis, especially liver metastasis, leading to a poor prognosis. Metabolic remodelling and epigenetic reprogramming are two important hallmarks of malignant tumours and participate in regulating PDAC tumorigenesis and metastasis. However, the interaction between these two processes during PDAC metastasis has not been fully elucidated.MethodsWe performed metabolomics analysis to identify the critical metabolites associated with PDAC liver metastasis and focused on guanidinoacetic acid (GAA). Intracellular GAA content was significantly increased in liver metastatic PDAC cells compared to primary cancer cells in mouse xenograft tumour models. The effects of GAA supplementation and glycine amidinotransferase (GATM) knockdown on PDAC metastasis were assessed by analysing cell migration, filopodia formation, epithelial-mesenchymal transition (EMT), and in vivo metastasis in different cell and animal models. Next, ChIP‒qPCR, 3C‒qPCR, and CRISPRi/dCas9-KRAB experiments were used to validate the “epigenome-metabolome" mechanism. Finally, the results of in vitro approaches, including RNA-seq, CUT&RUN, RT‒qPCR, and western blot analyses, as well as luciferase reporter gene assay and transwell assay, revealed the GAA-c-Myc-HMGA axis and transcription-activating histone modifications reprogramming.ResultsA high level of intracellular GAA was associated with PDAC liver metastasis. GAA could promote the migration, EMT, and liver metastasis of pancreatic cancer cells in vitro and in vivo. Next, we explored the role of GATM-mediated de novo GAA synthesis in pancreatic cancer metastasis. High expression of GATM was positively correlated with advanced N stage in PDAC. Knockdown of GATM significantly reduced the intracellular level of GAA, suppressed EMT, and inhibited PDAC liver metastasis, and these effects were attenuated by GAA supplementation. Mechanistically, we identified the active enhancers looped to the Gatm gene locus that promoted GATM expression and PDAC liver metastasis. Furthermore, we found that GAA promoted cell migration and EMT by regulating c-Myc-mediated high mobility group AT-hook protein expression. Moreover, GAA increased the H3K4me3 modification level by upregulating histone methyltransferases, which induced the transcription of metastasis-related genes, including Myc.ConclusionsThese findings revealed the critical role of the epigenome-metabolome interaction in regulating PDAC liver metastasis and suggested potential therapeutic strategies targeting GAA metabolism and epigenetic regulatory mechanisms.

Effects of guanidinoacetic acid supplementation on lactation performance, nutrient digestion and rumen fermentation in Holstein dairy cows.

Considering the high energy demand of lactation and the potential of guanidinoacetic acid (GAA) addition on the increase in creatine supply for cows, the present study investigated the effects of 0, 0.3, 0.6 and 0.9g kg-1 dry matter (DM) of GAA supplementation on lactation performance, nutrient digestion and ruminal fermentation in dairy cows. The study used 40 mid-lactation multiparous Holstein cows and the study duration was 100 days. DM intake was not affected, but milk and milk component yields and feed efficiency increased linearly with increasing GAA addition. The total-tract digestibility of DM, organic matter, neutral detergent fibre, acid detergent fibre and non-fibre carbohydrates increased linearly and that of crude protein increased quadratically with increasing GAA addition. When the addition level of GAA increased, ruminal pH, molar percentages of butyrate, isobutyrate and isovalerate and the acetate-to-propionate ratio decreased linearly, and the total volatile fatty acids concentration and propionate molar percentage also increased linearly, whereas the acetate molar percentage and ammonia-N concentration were unaltered. The activities of fibrolytic enzymes, α-amylase and protease increased linearly. The populations of total bacteria, fungi, Ruminococcus albus, Fibrobacter succinogenes, Ruminococcus flavefaciens, Ruminobacter amylophilus and Prevotella ruminicola increased linearly, whereas protozoa and methanogens decreased linearly with increasing GAA addition. As for the blood metabolites, concentrations of glucose, urea nitrogen and methionine were unchanged, total protein, albumin, creatine and homocysteine increased linearly, and folate decreased linearly with increasing GAA supply. The results of the present study indicate that supplementation of GAA improved milk performance and rumen fermentation in lactating dairy cows. © 2022 Society of Chemical Industry.

Guanidinoacetic acid supplementation: A narrative review of its metabolism and effects in swine and poultry

Guanidinoacetic acid (GAA) is an amino acid derivative and precursor for creatine which plays a significant role in energy metabolism. However, because of creatine’s instability during the manufacturing process and cost, GAA has been explored as an effective alternative to creatine supplements. GAA has been tested as a potential feed additive to enhance energy utilization and growth performance in the poultry and swine industries. Moreover, GAA has been combined with methionine to improve growth outcomes and may also act as an arginine-sparing agent in birds. The safety of the GAA supplements for animals, consumers, and the environment and its efficacy in numerous livestock species have been proven. This narrative review discusses the scientific evidence regarding the metabolism and effects of GAA supplementation in swine and poultry, identifying the knowledge gaps and future directions for further research on GAA supplementation. A systematic search of the literature identified published research findings related to GAA supplementation in swine and poultry and their findings are summarized in this narrative review to confirm the impacts of GAA supplementation on growth performance, reproductive performance, and meat quality in swine and poultry. Amongst its many demonstrated benefits, GAA is effective at improving body creatine concentration, growth parameters, feed conversion ratio, and performance of animals. Although GAA exerts many non-creatine roles, including the stimulation of insulin secretion, neuromodulation, and vasodilation, further research may require in-depth elaboration.

Effect of guanidinoacetic acid supplementation on nitrogen retention and methionine methyl group flux in growing steers fed corn-based diets.

Six ruminally cannulated Holstein steers (256 ± 14 kg) were used in a 6 × 6 Latin square design to assess effects of guanidinoacetic acid (GAA) supplementation on N retention and methionine (Met) methyl group flux in growing cattle fed corn-based diets. Factorial treatments were two levels of Met (0 or 5 g/d) and three levels of GAA (0, 7.5, or 15 g/d) delivered by continuous abomasal infusion. Periods were 10 d in length and included 6 d of treatment adaptation, 3 d for total fecal and urine collections, and 1 d for blood sampling and flux measurements. Urinary N linearly increased (P < 0.01) with GAA supplementation and decreased (P < 0.05) with Met supplementation. Fecal N excretion was unaffected (P ≥ 0.42) by treatment. Retained N was not affected by GAA supplementation, but it was increased (P < 0.01) by Met supplementation. Use of methionine for transmethylation reactions, as well remethylation of homocysteine, was not affected by GAA supplementation when Met was not supplemented, but tended to be linearly increased by GAA supplementation when Met was supplemented (GAA-linear × Met interaction; P = 0.07), with the increases matching the amount of GAA provided. This response suggests that methylation reactions for compounds other than GAA were reduced by GAA supplementation when Met supply was deficient. Plasma concentrations and urinary excretion of creatine increased linearly (P = 0.03 and P = 0.06, respectively) when GAA was supplemented. There was a linear increase (P < 0.01) in urinary GAA excretion with GAA supplementation. Neither plasma concentration nor urinary excretion of creatinine was affected (P ≥ 0.17) by treatment. No treatment differences (P ≥ 0.13) were observed for plasma haptoglobin concentrations. Plasma urea-N linearly increased (P < 0.05) with GAA supplementation. Concentrations of Met and taurine increased (P < 0.05) when Met was supplemented. Plasma arginine was greatest at the intermediate level of supplemental GAA (quadratic, P < 0.05). The increase in N retention when Met was supplemented demonstrates Met was limiting in the corn-based diet. Supplementation of GAA alone or with Met as a methyl donor did not increase N retention in growing steers, perhaps because creatine production was favored over protein deposition as a use for Met.

Effects of Guanidinoacetic Acid Supplementation on Productive Performance, Pectoral Myopathies, and Meat Quality of Broiler Chickens.

Simple SummaryGenetic selection for rapid growth is accompanied with challenges in meat quality such as pectoral myopathies, which lead to downgrading of breast muscle and economic losses for slaughterhouses. This experiment evaluated the effects of guanidinoacetic acid supplementation at rate of 0%, 0.06%, and 0.12% on the productive performance and meat quality of broiler chickens. Result showed that wooden breast was manifested by low creatine and high ultimate pH, and more associated with heavy birds. Guanidinoacetic acid supplementation increased muscle glycogen, reduced the ultimate pH, and reduced the incidence of wooden breast severity. In conclusion, guanidinoacetic acid can be used in broiler diets to improve the productive performance without exacerbating pectoral myopathy or affecting meat quality.The effects of guanidinoacteic acid (GAA) supplementation on productive performance, pectoral myopathies, and meat quality of broilers were studied. Treatments consisted of corn/soybean-based diets with a GAA supplement (0%, 0.06%, and 0.12%). A total of 546 one-day-old Ross-308 males were randomly allocated to 42 floor pens with 14 replicates (13 birds/pens) for each treatment. The results showed that GAA at doses of 0.06% and 0.12% improved feed conversion, increased the percentage of normal breast, and decreased the severity of wooden breast. Breast muscle myopathy severity was positively correlated with heavy birds and negatively correlated with breast muscle creatine and glycogen. Breast muscle creatine and glycogen correlated positively with normal, less severe pectoral myopathies and meat quality. In conclusion, GAA supplementation improved broiler performance without exacerbating pectoral myopathy or affecting meat quality.

Effects of guanidinoacetic acid supplementation on nitrogen retention and methionine flux in cattle.

Creatine stores high-energy phosphate bonds in muscle and is synthesized in the liver through methylation of guanidinoacetic acid (GAA). Supplementation of GAA may therefore increase methyl group requirements, and this may affect methyl group utilization. Our experiment evaluated the metabolic responses of growing cattle to postruminal supplementation of GAA, in a model where methionine (Met) was deficient, with and without Met supplementation. Seven ruminally cannulated Holstein steers (161 kg initial body weight [BW]) were limit-fed a soybean hull-based diet (2.7 kg/d dry matter) and received continuous abomasal infusions of an essential amino acid (AA) mixture devoid of Met to ensure that no AA besides Met limited animal performance. To provide energy without increasing the microbial protein supply, all steers received ruminal infusions of 200 g/d acetic acid, 200 g/d propionic acid, and 50 g/d butyric acid, as well as abomasal infusions of 300 g/d glucose. Treatments, provided abomasally, were arranged as a 2 × 3 factorial in a split-plot design, and included 0 or 6 g/d of l-Met and 0, 7.5, and 15 g/d of GAA. The experiment included six 10-d periods. Whole body Met flux was measured using continuous jugular infusion of 1-13C-l-Met and methyl-2H3-l-Met. Nitrogen retention was elevated by Met supplementation (P < 0.01). Supplementation with GAA tended to increase N retention when it was supplemented along with Met, but not when it was supplemented without Met. Supplementing GAA linearly increased plasma concentrations of GAA and creatine (P < 0.001), but treatments did not affect urinary excretion of GAA, creatine, or creatinine. Supplementation with Met decreased plasma homocysteine (P < 0.01). Supplementation of GAA tended (P = 0.10) to increase plasma homocysteine when no Met was supplemented, but not when 6 g/d Met was provided. Protein synthesis and protein degradation were both increased by GAA supplementation when no Met was supplemented, but decreased by GAA supplementation when 6 g/d Met were provided. Loss of Met through transsulfuration was increased by Met supplementation, whereas synthesis of Met from remethylation of homocysteine was decreased by Met supplementation. No differences in transmethylation, transsulfuration, or remethylation reactions were observed in response to GAA supplementation. The administration of GAA, when methyl groups are not limiting, has the potential to improve lean tissue deposition and cattle growth.

Effects of guanidinoacetic acid supplementation on zootechnical performance and some biometric indices in broilers challenged with T3-Hormone

The objective was to elucidate the effects of dietary guanidinoacetic acid (GAA) supplementation on broiler performance, serum enzymes, oxidative biomarkers, mitochondrial activities, carcase traits, gross lesion of cardiac muscle and liver histopathology in broilers challenged with T3-hormone. A total-of-192 one-day-old mixed sexed broilers were randomly assigned in a two factorial design, including two dietary treatments; control diet supplemented with or without T3-hormone (1.5 ppm) and GAA diet (0.06%) supplemented with or without T3-hormone (1.5 ppm). Each group was subdivided into eight replicates. Results showed interactions between GAAxT3-hormone. GAA diet significantly mitigated the negative effect of T3-hormone on serum total creatine kinase (CK), cardiac muscle (CK-MB), liver malondialdehyde (MDA) and superoxide dismutase (SOD), mitochondrial activities of cardiac muscle and liver histopathological lesion. In conclusion, GAA at a rate of 0.06% may have the potential to mitigate the negative effect of dietary T3-hormone but could not reduce the ascites mortality at such inclusion rate. HIGHLIGHTS GAA protected heart muscle. GAA mitigated the oxidative radicals in T3-hormone challenged birds. GAA modulated the mitochondrial activities in T3-hormone challenged birds.

Effects of guanidinoacetic acid supplementation on growth performance, nutrient digestion, rumen fermentation and blood metabolites in Angus bulls

Guanidinoacetic acid (GAA) can improve the growth performance of bulls. This study investigated the influences of GAA addition on growth, nutrient digestion, ruminal fermentation and serum metabolites in bulls. Forty-eight Angus bulls were randomly allocated to experimental treatments, that is, control, low-GAA (LGAA), medium-GAA (MGAA) and high-GAA (HGAA), with GAA supplementation at 0, 0.3, 0.6 and 0.9 g/kg DM, respectively. Bulls were fed a basal diet containing 500 g/kg DM concentrate and 500 g/kg DM roughage. The experimental period was 104 days, with 14 days for adaptation and 90 days for data collection. Bulls in the MGAA and HGAA groups had higher DM intake and average daily gain than bulls in the LGAA and control groups. The feed conversion ratio was lowest in MGAA and highest in the control. Bulls receiving 0.9 g/kg DM GAA addition had higher digestibility of DM, organic matter, NDF and ADF than bulls in other groups. The digestibility of CP was higher for HGAA than for LGAA and control. The ruminal pH was lower for MGAA, and the total volatile fatty acid concentration was greater for MGAA and HGAA than for the control. The acetate proportion and acetate-to-propionate ratio were lower for MGAA than for LGAA and control. The propionate proportion was higher for MGAA than for control. Bulls receiving GAA addition showed decreased ruminal ammonia N. Bulls in MGAA and HGAA had higher cellobiase, pectinase and protease activities and Butyrivibrio fibrisolvens, Prevotella ruminicola and Ruminobacter amylophilus populations than bulls in LGAA and control. However, the total protozoan population was lower for MGAA and HGAA than for LGAA and control. The total bacterial and Ruminococcus flavefaciens populations increased with GAA addition. The blood level of creatine was higher for HGAA, and the activity of l-arginine glycine amidine transferase was lower for MGAA and HGAA, than for control. The blood activity of guanidine acetate N-methyltransferase and the level of folate decreased in the GAA addition groups. The results indicated that dietary addition of 0.6 or 0.9 g/kg DM GAA improved growth performance, nutrient digestion and ruminal fermentation in bulls.

Dietary supplementation of guanidinoacetic acid for sows and their progenies: Performance, blood parameters and economic viability at nursery phase

The aim of this study was to evaluate the effects of guanidinoacetic acid supplementation for sows and their litter on performance, blood parameters and economic viability of piglets at nursery phase. A total of 80 high-prolific mixed-parity sows from 3rd and 4th parity were randomly distributed between two treatments: control diet and diet supplemented with 0.1% guanidinoacetic acid. Sows were fed with the dietary treatments during the gestation and lactation. Piglets were weaned at 23 days of age and then distributed in a randomized block design, in a 2 × 2 factorial arrangement, considering two diets for the sows during gestation and lactation (control diet and diet supplemented with 0.1% GAA) and two diets for the piglets at nursery phase (control diet and diet supplemented with 0.1% GAA). Each treatment consisted of six replicates, being the pen with 40 animals considered as experimental unit. No interaction between guanidinoacetic acid supplementation for sows during the gestation and lactation and for their progenies was observed (P>0.05) on performance and blood levels of creatinine and creatine kinase of the piglets during the nursery phase. The isolated factors also did not influence (P>0.05) these parameters. There was no interaction between guanidinoacetic acid supply for sows and their progenies on economic evaluation. Piglets that received dietary supplementation of 0.1% guanidinoacetic acid presented higher average feed cost per kilogram of body weight and cost index, and also lower economic efficiency index. Dietary supplementation of 0.1% guanidinoacetic acid for sows and their litters does not influence performance and blood parameters of piglets during the nursery phase, and is economically unfeasible.

The Effects of Guanidinoacetic Acid Supplementation on Muscle Creatine Content

The Effects of Guanidinoacetic Acid Supplementation on Muscle Creatine Content

Effects of Guanidinoacetic Acid Supplementation to Broiler Diets With Varying Energy Content

An experiment was conducted to determine the response of broiler chickens to guanidinoacetic acid (GAA) added to diets with different energy levels during fattening to 35 days of age. Ross 308 male chicks were allotted to 10 treatments, each consisting of six replicates of 140 birds/pen. Five maize-soyabean meal isonitrogenous diets with decreasing AMEn levels (100, 99, 98, 97 and 96% of requirement) with or without supplements of 0.6 g/kg CreAMINO® containing a minimum of 96% GAA were formulated. The criteria of response were feed intake, body weight gains, feed conversion ratio and carcass, breast meat, leg meat and abdominal fat yields. Supplementation of broiler diets with 0.06% GAA resulted in a significant (P < 0.05) decrease in voluntary feed intake. With decreasing AMEn level, voluntary feed intake and consequently protein and amino acid intakes increased which was manifested by improved growth performance (P < 0.01). GAA supplements significantly (P < 0.001) improved feed conversion ratio and efficiency of AMEn utilization and significantly (P < 0.01) increased breast meat yield. With decreasing AMEn level, the effects of GAA supplementation tended to diminish.

Effects of guanidinoacetic acid supplementation to broiler diets with varying energy contents

SUMMARY The purpose of this experiment was to determine the effect of guanidinoacetic acid (GAA) addition to diets containing different levels of ME on the growth performance, energy efficiency, and carcass yield of broiler chickens. A total of 1,536 straight-run Cobb 500 broilers were allocated to 24 floor pens (64 birds/pen). The dietary treatments consisted of a 3 × 2 factorial arrangement with different levels of ME [100% (2,988 kcal/kg of starter from 0 to 10 d, 3,083 kcal/kg of grower from 11 to 22 d, and 3,176 kcal/kg of finisher from 23 to 40 d), 95%, and 90% of the Cobb recommendation], with or without GAA (0.06%). Guanidinoacetic acid supplementation improved FCR from 23 to 40 d and 0 to 40 d of age (P ≤ 0.05) and reduced feed intake from 23 to 40 d of age (P ≤ 0.09), with no significant effects on BW gain. Body weight gain was significantly reduced when dietary energy was reduced by 10% from 11 to 22 d, 23 to 40 d, and 0 to 40 d of age (P ≤ 0.05). The energy reduction affected feed intake from 0 to 10 d and 11 to 22 d of age, with no effect during other periods. An interaction was found between energy level and GAA for FCR during the 0 to 40 d of the experiment. Addition of GAA improved the FCR of treatments with higher energy concentrations (100 and 95% of the management guide recommendation). The main effects of GAA supplementation and energy levels on carcass traits were not significant, except that addition of GAA reduced the percentage of liver significantly (P ≤ 0.05). The weight of the small intestine was reduced in the low-energy (90%) diets supplemented with GAA. Supplementation with GAA decreased caloric intake per kilogram of BW gain and per kilogram of carcass weight. It was concluded from the current experiment that GAA has the potential to improve FCR and energy efficiency.