Gamma-aminobutyric Acid Supplementation Research Articles

Gamma-aminobutyric acid supplementation improves olanzapine-induced insulin resistance by inhibiting macrophage infiltration in mice subcutaneous adipose tissue.

To investigate whether gamma-aminobutyric acid (GABA) supplementation improves insulin resistance during olanzapine treatment in mice and to explore the underlying mechanisms. Insulin resistance and body weight gain were induced in mice by 10 weeks of olanzapine treatment. Simultaneously, the mice were administered GABA after 4 weeks of olanzapine administration. We found that mice treated with olanzapine had lower GABA levels in serum and subcutaneous white adipose tissue (sWAT). GABA supplementation restored GABA levels and improved olanzapine-induced lipid metabolism disorders and insulin resistance. Chronic inflammation in adipose tissue is one of the main contributors to insulin resistance. We found that GABA supplementation inhibited olanzapine-induced adipose tissue macrophage infiltration and M1-like polarization, especially in sWAT. In vitro studies showed that stromal vascular cells, rather than adipocytes, were sensitive to GABA. Furthermore, the results suggested that GABA improves olanzapine-induced insulin resistance at least in part through a GABAB receptor-dependent pathway. These findings suggest that targeting GABA may be a potential therapeutic approach for olanzapine-induced metabolic disorders.

GABA Supplementation, Increased Heart-Rate Variability, Emotional Response, Sleep Efficiency and Reduced Depression in Sedentary Overweight Women Undergoing Physical Exercise: Placebo-Controlled, Randomized Clinical Trial

Gamma-aminobutyric acid (GABA) serves as a pivotal neurotransmitter implicated in the pathogenesis of stress, anxiety, sleep-related disorders, and heart rate (HR) reactions. Heart-rate variability (HRV), modulated by the sympathetic and parasympathetic branches of the autonomic nervous system (ANS), offers insights into cardiac autonomic control and cardiovascular well-being. The present study aimed to explore the impact of GABA supplementation on emotional metrics, sleep quality, and HRV in sedentary women with overweight or obesity partaking in physical exercise. A randomized, double-blind, placebo-controlled clinical trial was undertaken involving 30 sedentary women with overweight or obesity. Volunteers were assigned randomly to two groups: the intervention group receiving GABA (200 mg) once daily for a total of 90 supplementation doses, and the placebo group. Both groups engaged in physical exercise, while the supplementation regimen spanned 90 days. Assessments were conducted at three intervals: baseline (T0), midway through the study (T45), and study culmination (T90). Following 90 days of GABA supplementation, the intervention group demonstrated enhancements in habitual sleep efficiency, as indicated by reductions in Pittsburgh Sleep Quality Index (PSQI) scores. Moreover, an improved emotional response was observed, characterized by diminished negative affect. GABA supplementation yielded ameliorations in depression scores as per the Depression, Anxiety, and Stress Scale (DASS-21). Notably, an augmented HRV was noted, attributed to heightened parasympathetic autonomic nervous system predominance. GABA supplementation elicited noteworthy enhancements in heart rate variability, emotional response, depression mitigation, and sleep efficiency following a 90-day supplementation.

Influence of GABA (Gamma-aminobutyric acid) supplementation on biomass, pigments, lipid and protein content of Pseudochlorella pringsheimii under salinity stress

Microalgae synthesize valuable compounds like pigments, proteins, lipids and carbohydrates under stress conditions, which make them an interesting feedstock for different industries. The effect of GABA (Gamma-aminobutyric acid) supplementation under salinity stress conditions was investigated on growth, biomass, pigments, lipid and protein content of Pseudochlorella pringsheimii. Between the varying treatments, 5 g/L NaCl combined with 2.5 mM GABA was observed as the best concentration for stimulating the production of bioactive compounds in microalga P. pringsheimii. The results revealed a significant increase in biomass content by 93.24 %, compared with the control. Moreover, a significant increase was also observed in the production of chlorophyll (chl) a, chlorophyll (chl) b, total carotenoids (car), protein and lipid content by 112.15 %, 84 %, 29.94 %, 23.08 % and 35.63 %, respectively. However, as compared to control and salinity stress alone, the total carbohydrate content was sharply declined by 52.30 % and 101.79 % in GABA supplemented groups. In addition, the presence of fatty acids and different biomolecules were also confirmed by GC–MS and FTIR analysis. The existence of different essential and non-essential amino acids in substantial amounts was validated by UHPLC analysis. Collectively, the present work contributes to a novel strategy for boosting the coproduction of biomass, lipids, proteins and pigments in P. pringsheimii under unfavorable conditions.

Effect of dietary gamma aminobutyric acid (GABA) modulated the growth performance, immune and antioxidant capacity, digestive enzymes, intestinal histology and gene expression of Nile tilapia (Oreochromisniloticus)

Dietary GABA plays an important role in a variety of physiological functions in animals, but this has been rarely reported in fish. This study investigated the effects of dietary supplementation with GABA on growth, serum antioxidant indicators, digestive enzyme activities, intestinal morphology, and the gene expression of Nile tilapia. Diets containing three different GABA concentrations, 0 (control), 200 mg/kg (GABA200), and 500 mg/kg (GABA500), were fed to Nile tilapia (6.97 ± 0.34 g) for 56 days. The present study found that increasing dietary GABA content could increase the fish growth performance including final body weight, weight gain, specific growth rate, average daily gain, protein efficiency ratio, and feed efficiency compared to the control diet. Interestingly, the feed conversion ratio was improved by dietary GABA supplementation. The antioxidant enzyme activities against ammonia stress of fish fed the GABA diets were significantly higher than the corresponding control group throughout the 96-h ammonia exposure. Moreover, significant increases in digestive enzyme activities including protease, amylase and lipase were found in fish fed the GABA diets. Intestinal morphology analysis revealed increased heights and widths of intestinal villi as well as thickness of the intestinal muscularis in fish fed the GABA diets compared to the control diet. The supplementation of diets with GABA significantly increased the expression level of immune- and growth-related genes. The above results indicate that dietary GABA can modulate the growth, improve their immune response and antioxidant status, gut health and morphology and gene expression of Nile tilapia. Therefore, GABA is a promising feed additive for Nile tilapia aquaculture.

Gamma-amino butyric acid (GABA) supplementation alleviates dexamethasone treatment-induced oxidative stress and inflammation response in broiler chickens

This experiment was conducted to investigate the effect of Gamma-amino butyric acid (GABA) on growth performance, serum and liver antioxidant status, inflammation response and hematological changes, in male broiler chickens under experimentally induced stress via in-feed dexamethasone (DEX). A total of 300 male chicks (Ross 308) on day 7 after hatching, were randomly selected into four groups which were positive control group (PC, without any treatment), negative control (NC, with 1 mg/kg DEX), a third group received 1 mg/kg DEX and 100 mg/kg GABA (DG +) and the last one was (DG ++) which received 1 mg/kg DEX and 200 mg/kg GABA. Each group has five replicates (15 birds/replicate). Dietary GABA modulated DEX-induced adverse effects on body weight, feed intake, and feed conversion ratio. The DEX-induced effect of serum levels of IL-6 and IL-10 was reduced by dietary GABA supplementation. The activity of serum and liver superoxide dismutase, catalase, glutathione peroxidase were enhanced and malondialdehyde was reduced by GABA supplementation. The serum levels of total cholesterol & triglyceride were higher while low-density lipoprotein & high-density lipoprotein were lower in GABA groups than NC group. GABA supplementation also significantly decreased the heterophil, heterophil/lymphocyte ratio and elevated the activities of aspartate aminotransferase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) than NC group. In conclusion, dietary GABA supplementation can alleviate DEX stress-induced oxidative stress and inflammation response.

Maternal Dietary Supplementation with γ-Aminobutyric Acid Alleviated Oxidative Stress in Gestating Sows and Their Offspring by Regulating GABRP.

Simple SummarySows usually suffer oxidative stress during gestation, and this limits the growth of fetuses via placenta. Gamma-aminobutyric acid (GABA) is a functional nonessential amino acid engaged in regulating the physiological status of animals. However, the effects of GABA on the oxidative homeostasis of sows and their offspring remain unclear. This study aims to investigate the effects of GABA on the oxidative stress of gestating sows, newborn piglets, as well as the H2O2-treated porcine trophectoderm cell line-2 (pTr-2 cells) and to subsequently provide guidance on the application of GABA in sows’ nutrition during late gestation. We found that GABA alleviated placental oxidative stress in gestating sows by increasing antioxidant-associated enzyme activity and by upregulating the gene expressions of gamma-aminobutyric acid receptor (GABRP) and nuclear factor-erythroid 2-related factor-2 (Nrf2) in pTr-2 cells, as well as enhanced the antioxidant capacity of sows and fetal piglets. This study provides the possibility for future application of GABA in maternal–fetal nutrition.Sows usually suffer oxidative stress during gestation, and this limits the growth of fetuses via placenta. Gamma-aminobutyric acid (GABA) is a functional nonessential amino acid engaged in regulating the physiological status of animals. However, the effects of GABA on the oxidative homeostasis of sows and their offspring remain unclear. Eighteen late gestating sows (85 d) were divided into the CON and GABA groups and fed the basal diet and the GABA diet (200 mg/kg GABA), respectively, until farrowing. At parturition, the sows’ litter characteristics, the plasma antioxidant parameters of sows, and their offspring were evaluated. The results showed that GABA supplementation had no marked effect on the reproductive performance of sows (p > 0.10) but had a trend of reducing the amount of intrauterine growth restriction (IUGR) in piglets (0.05 < p < 0.10). At the same time, the addition of GABA elevated the plasma superoxide dismutase (SOD) level of sows and enhanced the glutathione peroxidase (GSH-Px) activity of newborn piglets (p < 0.05). Based on the H2O2-induced oxidative stress in pTr-2 cells, GABA elevated intracellular GSH-Px, SOD, catalase (CAT), and total antioxidant capacity (T-AOC, p < 0.01) and upregulated the gene expressions of CAT, gamma-aminobutyric acid receptor (GABRP), and nuclear factor-erythroid 2-related factor-2 (Nrf2) in H2O2-treated pTr-2 cells (p < 0.05). Taken together, GABA improved the antioxidant capacity of sows and alleviated the placental oxidative stress by upregulating the GABRP and Nrf2 genes, which have the potential to promote oxidative homeostasis in newborn piglets.

Gamma-aminobutyric acid enhances hypoxia tolerance of juvenile Chinese mitten crab (Eriocheir sinensis) by regulating respiratory metabolism and alleviating neural excitotoxicity

With climate change and intensive aquaculture development, environmental hypoxia in aquaculture water has become a common challenge for many aquatic species. Therefore, it is crucial to improve the hypoxic tolerance of animals through nutritional strategies. This study explored the positive role of dietary gamma-aminobutyric acid (GABA) supplementation in enhancing hypoxia tolerance of juvenile Eriocheir sinensis through respiratory regulation and alleviation of hypoxia-induced neural excitotoxicity. Acute hypoxia stress significantly up-regulated the mRNA expression level of hypoxia-inducible factor 1α, oxygen consumption rate and anaerobic respiratory metabolism-related enzyme activities. On the other hand, aerobic respiratory metabolism-related enzyme activities were significantly decreased. However, dietary GABA supplementation remodeled the respiratory metabolism pattern of juvenile crabs exposed to hypoxia stress. In addition, acute hypoxic stress significantly increased the contents of free glutamate and GABA in the nervous tissue. The expression levels of N-Methyl-d-aspartate-related receptor genes and calcium-dependent degradation enzyme-related genes were significantly up-regulated. Similarly, neuronal apoptosis rates, expression levels of apoptosis-related genes, and vesicular glutamate transporter genes were also significantly increased. The high-affinity neuronal glutamate transporter decreased significantly in the crabs exposed to hypoxia stress. However, dietary GABA supplementation could effectively prevent acute hypoxia stress-induced neural excitotoxicity. Furthermore, dietary GABA could significantly improve the redox status in vivo exposed to hypoxia stress. In conclusion, acute hypoxia stress can affect respiratory metabolism and redox state and induce neural excitotoxicity in juvenile E. sinensis. GABA supplementation could improve hypoxia tolerance through multiple physiological regulation pathways.

Potential benefits of exogenous neurotransmitters in alleviating transport stress in koi carp, Cyprinus carpio

The transport of live fish is an important process in the ornamental fish trade. As such, reducing transport stress plays a vital role in improving fish survival and minimizing economic losses. The objective of this study was to assess the efficacy of exogenous neurotransmitters in alleviating transport stress in koi carp, Cyprinus carpio. First, fish were subjected to simulated transport, and samples were collected at 0, 4, 6, 12, 24, and 48 h for the determination of water quality parameters and serum indices. The results indicated that the pH of the water decreased and ammonium nitrogen (NH4-N) was enhanced with the increase of transport time. The most significant changes in stress-related indices were observed at 4 h after transport, and thus the subsequent transport experiments were scheduled for 4 h. Three types of exogenous neurotransmitters were added to the water, and fish were transported for 4 h to determine the efficacy of the neurotransmitters. Gamma-aminobutyric acid (GABA) increased the pH, and decreased the NH4-N content of the water. The concentrations of serum adrenaline, cortisol, and glucose were decreased by GABA supplementation. Guanidine acetic acid (GAA) increased the pH of the water, and decreased the concentrations of serum adrenaline and cortisol. The addition of 5-hydroxytryptamine (5-HT) lowered the NH4-N level of the water, and decreased the concentrations of serum adrenaline and cortisol in the fish. In conclusion, the addition of exogenous neurotransmitters to transport water may help to alleviate transport stress by improving water quality and depressing the enhancement of stress-related hormones.

Dietary gamma-aminobutyric acid (GABA) improves non-specific immunity and alleviates lipopolysaccharide (LPS)-induced immune overresponse in juvenile Chinese mitten crab (Eriocheir sinensis)

Inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is an immunomodulator to inhibit immune-mediated pro-inflammatory response and has been used to treat various immune-related diseases in mammals. However, the immunoregulatory effect of GABA in crustaceans has not been reported. This study evaluates the regulatory effect of dietary GABA supplementation on the innate immune status and immunoregulatory potential in lipopolysaccharide (LPS)-induced immune response in juvenile Eriocheir sinensis. Juvenile crabs were fed with six diets supplemented with graded GABA levels (0, 40, 80, 160, 320 and 640 mg/kg dry matter) for 8 weeks and then 24 h LPS challenge test was carried out. The results showed that dietary GABA supplementation significantly decreased mortality at 4 and 8 weeks. Moreover, the hemocyanin content, acid phosphatase, and alkaline phosphatase activities significantly increased in the crabs fed GABA supplementation compared with the control. On the contrary, the alanine aminotransferase and alanine aminotransferase activities in serum decreased significantly in the GABA supplementation groups compared with the control. Similarly, superoxide dismutase activity, glutathione content, and the transcriptional expression of the antioxidant-related genes and immune-related genes were significantly higher in the GABA supplementation groups than in the control. In addition, the mRNA expressions of anti-lipopolysaccharide factors (ALF 1, ALF 2, ALF 3) and inflammatory signaling pathways related genes (TLR, Myd88, Relish, LITAF, P38-MAPK, ADAM17) were significantly up-regulated in LPS stimulation groups compared with PBS treatment. Meanwhile, pro-apoptosis-related genes' mRNA expressions were significantly up-regulated, and anti-apoptosis-related genes were significantly down-regulated under LPS stimulation compared with PBS treatment. However, GABA pretreatment effectively alleviated LPS-induced immune overresponse and apoptosis. Therefore, this study demonstrates that dietary GABA supplementation could be used as an immunomodulator to improve the non-specific immunity and antioxidant capacity and alleviate the immune-mediated immune overresponse of juvenile E. sinensis.

GABA and Fermented Curcuma longa L. Extract Enriched with GABA Ameliorate Obesity through Nox4-IRE1α Sulfonation-RIDD-SIRT1 Decay Axis in High-Fat Diet-Induced Obese Mice.

Gamma-aminobutyric acid (GABA) is a natural amino acid with antioxidant activity and is often considered to have therapeutic potential against obesity. Obesity has long been linked to ROS and ER stress, but the effect of GABA on the ROS-associated ER stress axis has not been thoroughly explored. Thus, in this study, the effect of GABA and fermented Curcuma longa L. extract enriched with GABA (FCLL-GABA) on the ROS-related ER stress axis and inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) sulfonation were examined with the HFD model to determine the underlying anti-obesity mechanism. Here, GABA and FCLL-GABA supplementations significantly inhibited the weight gain in HFD fed mice. The GABA and FCLL-GABA supplementation lowered the expressions of adipogenic transcription factors such as PPAR-γ, C/EBPα, FAS, and SREBP-1c in white adipose tissue (WAT) and liver from HFD-fed mice. The enhanced hyper-nutrient dysmetabolism-based NADPH oxidase (Nox) 4 and the resultant IRE1α sulfonation-RIDD-SIRT1 decay under HFD conditions were controlled with GABA and FCLL-GABA. Notably, GABA and FCLL-GABA administration significantly increased AMPK and sirtuin 1 (SIRT1) levels in WAT of HFD-fed mice. These significant observations indicate that ER-localized Nox4-induced IRE1α sulfonation results in the decay of SIRT1 as a novel mechanism behind the positive implications of GABA on obesity. Moreover, the investigation lays a firm foundation for the development of FCLL-GABA as a functional ingredient.

Dietary gamma-aminobutyric acid supplementation does not mitigate stress responses in weaner pigs given adrenocorticotropic hormone and experimentally infected with enterotoxigenic Escherichia coli

Gamma-aminobutyric acid (GABA) is a non-protein amino acid, a major inhibitory neurotransmitter in the central nervous system that stimulates feed intake and inhibits the hypothalamic-pituitary-adrenal (HPA) axis. We hypothesised that: (1) GABA supplementation in the diet would reduce markers of the stress response in weaned pigs injected with adrenocorticotropic hormone (ACTH) and inoculated with enterotoxigenic Escherichia coli (ETEC); and (2) this reduction in stress responses would improve performance after weaning. A total of 96 newly-weaned male pigs (Large White x Landrace) were stratified into a two by four factorial arrangement with respective factors being (i) with/without ACTH injection and ETEC infection (challenge versus non-challenge) and (ii) four dietary GABA levels (0, 60, 80, 100 mg/kg). On days 8 and 9 after weaning, piglets were orally inoculated with ETEC (0.8 ml via two gelatinized capsules; serotype O149; F4) as well as being given 5 IU ACTH intramuscularly (IM), which occurred an hour before ETEC inoculation. Pigs in the non-challenged group were given IM 0.2 mL of sterile saline and sham infected with two capsules of PBS. Faecal consistency scores were recorded daily, pigs and feed were weighed weekly to determine performance and blood samples were collected at days 6, 9 and 14. GABA supplementation did not reduce plasma cortisol. However challenged pigs had higher levels compared to the non-challenge group at day 9 (P = 0.001). Performance was not influenced by GABA supplementation (P > 0.05). Between days 8–14, 54.3% of pigs in the challenge group developed diarrhoea compared to 5.6% in the non-challenged group (P = 0.001). These data indicate that eliciting both an ETEC infection challenge and an acute stress response after weaning initiated an endocrine stress response. The use of GABA in feed did not reduce this stress response, reduce diarrhoea or improve production performance.

Gamma-Aminobutyric Acid (GABA) Promotes Growth in Zebrafish Larvae by Inducing IGF-1 Expression via GABAA and GABAB Receptors.

Insulin-like growth factor-1 (IGF-1) primarily increases the release of gamma-aminobutyric acid (GABA) in neurons; moreover, it is responsible for the promotion of longitudinal growth in children and adolescents. Therefore, in this study, we investigated whether exogenous GABA supplementation activates IGF-mediated growth performance. Zebrafish larvae treated with GABA at three days post fertilization (dpf) showed a significant increase in the total body length from 6 to 12 dpf through upregulation of growth-stimulating genes, including IGF-1, growth hormone-1 (GH-1), growth hormone receptor-1 (GHR-1), and cholecystokinin A (CCKA). In particular, at 9 dpf, GABA increased total body length from 3.60 ± 0.02 to 3.79 ± 0.03, 3.89 ± 0.02, and 3.92 ± 0.04 mm at concentrations of 6.25, 12.5, and 25 mM, and the effect of GABA at 25 mM was comparable to 4 mM β-glycerophosphate (GP)-treated larvae (3.98 ± 0.02 mm). Additionally, the highest concentration of GABA (50 mM) -induced death in 50% zebrafish larvae at 12 dpf. GABA also enhanced IGF-1 expression and secretion in preosteoblast MC3T3-E1 cells, concomitant with high levels of the IGF-1 receptor gene (IGF-1R). In zebrafish larvae, the GABA-induced growth rate was remarkably decreased in the presence of an IGF-1R inhibitor, picropodophyllin (PPP), which indicates that GABA-induced IGF-1 enhances growth rate via IGF-1R. Furthermore, we investigated the effect of GABA receptors on growth performance along with IGF-1 activation. Inhibitors of GABAA and GABAB receptors, namely bicuculline and CGP 46381, respectively, considerably inhibited GABA-induced growth rate in zebrafish larvae accompanied by a marked decrease in the expression of growth-stimulating genes, including IGF-1, GH-1, GHR-1, and CCKA, but not with an inhibitor of GABAC receptor, TPMPA. Additionally, IGF-1 and IGF-1R expression was impaired in bicuculline and CGP 46381-treated MC3T3-E1 cells, but not in the cells treated with TPMPA. Furthermore, treatment with bicuculline and CGP 46381 significantly downregulated GABA-induced IGF-1 release in MC3T3-E1 cells. These data indicate that GABA stimulates IGF-1 release via GABAA and GABAB receptors and leads to growth promotion performance via IGF-1R.

Dietary gamma-aminobutyric acid (GABA) supplementation increases food intake, influences the expression of feeding-related genes and improves digestion and growth of Chinese mitten crab (Eriocheir sinensis)

Animal growth performance is determined by food intake, digestion and nutrient absorption and the complex central and peripheral nerves may regulate the quantity of food intake. This study evaluates the effects of gamma-aminobutyric acid (GABA) supplements in purified diets on the growth performance, food intake and digestive ability of juvenile Chinese mitten crab Eriocheir sinensis, and the possible mechanism of neuromodulation. A total of 1200 juvenile crabs (0.77 ± 0.02 g) were fed with six diets supplemented with graded GABA levels (0, 40, 80, 160, 320 and 640 mg/kg dry matter) for 8 weeks. Each diet group had five replicates, and each replicate had 40 crabs in a tank (100 × 80 × 60 cm). The weight gain, specific growth rate, molting frequency, and the activities of digestion (α-amylase, trypsin and lipase) and absorption (Na+-K+-ATPase and γ- glutamyl transferase) enzymes were significantly increased by moderate dietary GABA supplementation compared with the 0 mg/kg GABA supplementation group. Furthermore, the food intake of juvenile E. sinensis was significantly increased with moderate dietary GABA supplementation compared with the 0 mg/kg GABA supplementation group. The qRT-PCR results showed that the expression of the orexigenic neural signal-related genes was significantly up-regulated, and the anorexigenic neural signal-related genes were significantly down-regulated in the cranial ganglia, thoracic ganglia and intestine tissues. Meanwhile, the expressions of the main genes involved in taste modulation and reward regulation were significantly up-regulated, whereas the expression of genes related to punishment regulation was significantly down-regulated in cranial ganglia and thoracic ganglia. Two-slope broken-line regression analysis of specific growth rate and weight gain against the dietary GABA levels showed that dietary GABA at the optimal dietary level was 84–89 mg/kg, and this level can improve growth performance, food intake, digestion and absorption in juvenile E. sinensis. GABA might act as an orexigenic neural signal or work with other appetite-related nerve signals to promote food intake by participating in regulating the satiety circuit and the reward circuit.

The effect of gamma-aminobutyric acid supplementation on growth performances, immune responses, and blood parameters of chickens reared under stressful environment: a meta-analysis.

Gamma-aminobutyric acid (GABA) is a well-known feed supplement for its capability of reducing the adverse effect of stress in chickens. Several studies using GABA supplementation as a mitigatory measure have been published. However, it remains difficult to draw a general conclusion since these studies have been done under different experimental conditions. Therefore, the objective of this study was to quantify the response (growth performances, immune responses, and blood biochemical parameters) of chickens to GABA supplementation under various stressful conditions through a meta-analysis approach. A total of 19 articles published from 2011 to 2020, including 30 treatments, were used. A mixed-model ANOVA was used to assess how the growth parameters varied based on the GABA mode of supplementation. Linear mixed models and general linear models were used to evaluate the effects of the GABA doses and the duration of the supplementation on the growth performances and the immune parameters. Results indicated that supplementation of GABA via drinking water was more effective than dietary supplementation for reducing the feed conversion ratio in heat-stressed birds (P < 0.01). In addition, an increase in the GABA doses resulted in an augmentation (P < 0.01) of the body weight gain while a longer duration of supplementation resulted in increasing (P<0.01) the feed intake. Furthermore, increasing the duration of the supplementation reduced the immunoglobulin (P < 0.0001) and bursa's relative weight (P < 0.0001), while increasing blood CD8+ count (P < 0.001) and spleen's relative weight (P < 0.0001). Finally, blood total protein content was increased (P < 0.0001) by a longer duration of supplementation. This study showed that the doses and the duration of the GABA supplementation can affect the growth performances of chickens under stressful conditions. However, the effect of GABA on immune responses and blood parameters is perceived with a relatively longer supplementation duration.

Dietary GABA enhances hypoxia tolerance of a bottom-dwelling carp, Cirrhinus mrigala by modulating HIF-1α, thyroid hormones and metabolic responses.

The Indian major carp, mrigal (Cirrhinus mrigala), is a bottom-dwelling fish that can survive hypoxic episodes in its natural environment. We hypothesise that it can better survive hypoxic conditions by altering metabolic responses through GABA (Gamma-aminobutyric acid) supplementation. In the first experiment, the hypoxia tolerance time of the fishes was evaluated under extreme anoxic conditions after feeding with GABA, which showed that GABA had improved survival time under hypoxia. To study the response of dietary GABA in hypoxia-exposed fish, the branchial HIF-1α expression levels, serum thyroid hormone levels and hepatic metabolic responses were assessed in the subsequent experiment. The treatment groups were fed for 60 days with experimental diets containing 4 levels of GABA (0.00% G, 0.50% G, 0.75% G and 1.0%G) and were subjected to 72-h hypoxia exposure (0.5 ± 0.02 mg L-1 dissolved oxygen (DO)) whereas a control group was maintained under normoxic conditions (6.0 ± 0.21 mg L-1 DO). The five treatment groups with three replicates were C0 (0% G + normoxia), H0 (0% G + hypoxia), H0.5 (0.50% G + hypoxia), H0.75 (0.75% G + hypoxia) and H1.0 (1.00% G + hypoxia). The results indicated that GABA supplementation triggered downregulation of HIF 1 alpha expression. When compared with the control group, decreased thyroxine (T4) and triiodothyronine (T3) levels were observed in the GABA-fed hypoxic groups. However, TSH (thyroid stimulating hormone) level remained unchanged in all the treatments. The LDH (lactate dehydrogenase) level in hypoxia-exposed groups was decreased by GABA supplementation. Our study demonstrated that GABA supplementation restores acute hypoxia-induced HIF-1α expression, thyroid hormone levels and LDH activities. On the other hand, it enhanced the citrate synthase (CS) activities at 0.5-1.00%, which showed a sharp decline in hypoxia. Hypoxia caused increase in the serum metabolites such as glucose, lactate, cholesterol and triglycerides. However, GABA supplementation was partially effective in reducing glucose and lactate level while triglycerides and cholesterol values remained unchanged. Overall, our results suggested a potential role of GABA in suppressing metabolism during hypoxia exposure, which can increase the chances of survival of the species Cirrhinus mrigala during hypoxia.

Effects of dietary gamma-aminobutyric acid in juvenile Nile tilapia, Orechromis niloticus

Abstracts The present study was conducted to evaluate the effects of different dietary gamma-aminobutyric acid (GABA) levels in Nile tilapia, Orechromis niloticus. Six groups of fish averaging 3.03 ± 0.07 g (mean ± SD) were randomly distributed in 18 rectangular tanks in triplicates. A basal diet without GABA supplementation was used as a control (CON), and the other five diets were prepared by adding 75 mg GABA (GABA144), 75 mg GABA +50 mg heat-killed Lactobacillus paracasei (GABA189L), 150 mg GABA (GABA197), 150 mg GABA +50 mg heat-killed Lactobacillus paracasei (GABA242L), and 600 mg GABA (GABA507) per kg of diet. Actual GABA compositions for CON, GABA144, GABA189L, GABA197, GABA242L and GABA507 diets were 96, 144, 189, 197, 242 and 507 mg kg−1, respectively. After 8 weeks of experiment, weight gain, specific growth rate, feed efficiency and protein efficiency ratio of fish fed GABA189L were significantly higher than those of fish fed CON and GABA5.7 diets (P

Oral Supplementation Using Gamma-Aminobutyric Acid and Whey Protein Improves Whole Body Fat-Free Mass in Men After Resistance Training.

BackgroundOral gamma-aminobutyric acid (GABA) supplementation increases growth hormone (GH) serum levels and protein synthesis. Therefore, post-exercise supplementation using GABA and protein may help enhance training-induced muscle hypertrophy. We evaluated whether GABA with whey protein enhanced muscular hypertrophy in men after progressive resistance training.MethodsTwenty-one healthy men (26 - 48 years) were randomized to receive whey protein (WP; 10 g) or whey protein + GABA (WP + GABA; 10 g + 100 mg) daily for 12 weeks. Both groups performed resistance training twice per week (three sets of 12 repetitions at 60% of maximal strength; leg press, leg extension, leg curl, chest press, and pull down). Body composition was assessed using dual-energy X-ray absorptiometry.ResultsIn the WP + GABA group, resting plasma GH concentrations were significantly elevated at 4 and 8 weeks, compared to baseline. However, resting plasma GH concentrations in the WP group were only significantly elevated at 8 weeks. After 12 weeks, the WP + GABA group exhibited significantly greater increase in whole body fat-free mass than the WP group.ConclusionsThe GABA and whey protein combination was more effective for increasing whole body fat-free mass; daily GABA supplementation may help enhance exercise-induced muscle hypertrophy.

Application of gamma-aminobutyric acid increased the level of phytohormones in Citrus sinensis.

In the current study, we showed that exogenous GABA supplementation increases the endogenous GABA level, several amino acids, and phytohormones in citrus plants, suggesting that GABA works in harmony with phytohormones. Gamma-aminobutyric acid (GABA) plays a key role in cytosolic regulation of pH, controlling of carbon and nitrogen metabolism, and protection against biotic and abiotic stresses. Although it is well-known that GABA is implicated in plant defense and it could act as a signaling molecule, its effect on phytohormones is not completely understood. In this study, we investigated the effect of exogenous GABA on citrus phytohormones using gas chromatography-mass spectrometry. A significant increase in endogenous GABA was observed in GABA-treated plants. The highest increase in GABA was recorded in plants treated with 10mM7days post-treatment. In addition, we observed a moderate increase in several amino acids including glycine, L-alanine, L-proline, L-asparagine, and L-glutamine. The levels of benzoic acid, cinnamic acid, salicylic acid, trans-jasmonic acid, indole acetic acid, indole propionic acid, and abscisic acid were significantly increased in GABA-treated plants compared to the control. The gene expression showed that GABA transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH) were induced in GABA-treated plants, indicating a conversion of GABA to succinate. In addition, the gene expression of the regulatory enzymes of the TCA cycle (malate dehydrogenase and succinic dehydrogenase) was upregulated in GABA-treated plants, indicating an induction of respiration. In agreement with the chemical analysis, the gene expression results showed that most of the genes implicated in the biosynthesis of phytohormones were also upregulated in GABA-treated plants. Our results indicated that GABA works in harmony with phytohormones and suggested that regulation of phytohormones by exogenous GABA could play a key role in reducing plant stress.

Supplementation of gamma-aminobutyric acid (GABA) affects temporal, but not spatial visual attention

In a randomized, double-blind, and placebo-controlled experiment, the acute effects of gamma-aminobutyric acid (GABA) supplementation on temporal and spatial attention in young healthy adults were investigated. A hybrid two-target rapid serial visual presentation task was used to measure temporal attention and integration. Additionally, a visual search task was used to measure the speed and accuracy of spatial attention. While temporal attention depends primarily on the distribution of limited attentional resources across time, spatial attention represents the engagement and disengagement by relevant and irrelevant stimuli across the visual field. Although spatial attention was unaffected by GABA supplementation altogether, we found evidence supporting improved performance in the temporal attention task. The attentional blink was numerically, albeit not significantly, attenuated at Lag 3, and significantly fewer order errors were committed at Lag 1, compared to the placebo condition. No effect was found on temporal integration rates. Although there is controversy about whether oral GABA can cross the blood-brain barrier, our results offer preliminary evidence that GABA intake might help to distribute limited attentional resources more efficiently, and can specifically improve the identification and ordering of visual events that occur in close temporal succession.

Rescuing fluoride-induced damages in liver with gamma aminobutyric acid

Fluorine poisoning affects human health all over the world and an urgent task is to develop alleviative medicine to recover or ameliorate the damages to the body. Here we studied the effects of gamma-aminobutyric acid (GABA), a liver protector reported previously, on fluoride-induced damage in the mouse liver. Through microscope imaging of the liver tissue, TUNEL immunostaining, real-time RT-PCR, enzyme immunoassay and colorimetric method, we found that GABA supplementation prevented the metabolic toxicity caused by fluoride treatment in mice. This detoxification was reflected by the reduced oxidative stress and apoptosis, enhanced neuron protection and liver function. Collectively, this study provided evidence of the beneficial effects of GABA supplement on liver damage, implicating its therapeutic potential in fluorosis.