scholarly journals Branched-chain amino acids govern the high learning ability phenotype in Tokai high avoider (THA) rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yukari Shida ◽  
Hitoshi Endo ◽  
Satoshi Owada ◽  
Yutaka Inagaki ◽  
Hideaki Sumiyoshi ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Interindividual Variability ◽  
Nutritional Supplements ◽  
Brain Dysfunction ◽  
Learning Ability ◽  
Metabolomic Analysis ◽  
High Learning ◽  
Learning Capacity ◽  
Branched Chain Amino Acid ◽  
Branched Chain

AbstractTo fully understand the mechanisms governing learning and memory, animal models with minor interindividual variability and higher cognitive function are required. THA rats established by crossing those with high learning capacity exhibit excellent learning and memory abilities, but the factors underlying their phenotype are completely unknown. In the current study, we compare the hippocampi of parental strain Wistar rats to those of THA rats via metabolomic analysis in order to identify molecules specific to the THA rat hippocampus. Higher branched-chain amino acid (BCAA) levels and enhanced activation of BCAA metabolism-associated enzymes were observed in THA rats, suggesting that acetyl-CoA and acetylcholine are synthesized through BCAA catabolism. THA rats maintained high blood BCAA levels via uptake of BCAAs in the small intestine and suppression of BCAA catabolism in the liver. Feeding THA rats with a BCAA-reduced diet decreased acetylcholine levels and learning ability, thus, maintaining high BCAA levels while their proper metabolism in the hippocampus is the mechanisms underlying the high learning ability in THA rats. Identifying appropriate BCAA nutritional supplements and activation methods may thus hold potential for the prevention and amelioration of higher brain dysfunction, including learning disabilities and dementia.

scholarly journals Metabolomic Analysis of the Effects of Leptin Replacement Therapy in Patients with Lipodystrophy

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Shivraj Grewal ◽  
Sriram Gubbi ◽  
Andin Fosam ◽  
Caroline Sedmak ◽  
Shanaz Sikder ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Metabolomic Analysis ◽  
Metabolomic Profiling ◽  
Branched Chain Amino Acid ◽  
Before And After ◽  
Branched Chain

Abstract Context and Objective Leptin treatment has dramatic clinical effects on glucose and lipid metabolism in leptin-deficient patients with lipodystrophy. Further elucidation of metabolic effects of exogenous leptin therapy will shed light on understanding leptin physiology in humans. Our objective was to utilize metabolomic profiling to examine the changes associated with administration of short-term metreleptin therapy in patients with lipodystrophy. Study Design We conducted a pre-post-treatment study in 19 patients (75% female) with varying forms of lipodystrophy (congenital generalized lipodystrophy, n = 10; acquired generalized lipodystrophy, n = 1; familial partial lipodystrophy, n = 8) who received daily subcutaneous metreleptin injections for a period of 16 to 23 weeks. A 3-hour oral glucose tolerance test and body composition measurements were conducted before and after the treatment period, and fasting blood samples were used for metabolomic profiling. The study outcome aimed at measuring changes in physiologically relevant metabolites before and after leptin therapy. Results Metabolomic analysis revealed changes in pathways involving branched-chain amino acid metabolism, fatty acid oxidation, protein degradation, urea cycle, tryptophan metabolism, nucleotide catabolism, vitamin E, and steroid metabolism. Fold changes in pre- to post-treatment metabolite levels indicated increased breakdown of fatty acids, branched chain amino acids proteins, and nucleic acids. Conclusions Leptin replacement therapy has significant effects on important metabolic pathways implicated in patients with lipodystrophy. Continued metabolomic studies may provide further insight into the mechanisms of action of leptin replacement therapy and provide novel biomarkers of lipodystrophy. Abbreviations: 1,5-AG, 1,5-anhydroglucitol; 11βHSD1, 11-β hydroxysteroid dehydrogenase 1; BCAA, branched-chain amino acid; FFA, free fatty acid; GC-MS, gas chromatography mass spectrometry; IDO, indoleamine 2,3-dioxygenase; IFN-γ, interferon-γ; m/z, mass to charge ratio; OGTT, oral glucose tolerance test; TDO, tryptophan 2,3-dioxygenase; TNF-α, tumor necrosis factor-α; UPLC-MS/MS, ultra-performance liquid chromatography-tandem mass spectrometry.

scholarly journals Quantitative Analysis of Branched-chain Amino Acids in Five Nutritional Supplements Using a Leucine Dehydrogenase Assay (P23-004-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Brendan Eley
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Nutritional Supplements ◽  
Sport Nutrition ◽  
Free Form ◽  
Leucine Dehydrogenase ◽  
Funding Sources ◽  
Branched Chain Amino Acid ◽  
Branched Chain ◽  
The Given

Abstract Objectives The objective of this experiment was to determine the branched-chain amino acid (BCAA) content in five different sport nutrition supplements compared to the amount claimed on the label. Methods To measure the BCAA content of five nutritional supplements, a leucine dehydrogenase enzyme assay was used. This enzyme catalyzes the reaction of turning the given BCAA (L-leucine, L-valine, and L-isoleucine), water, and NAD+ into their respective metabolite, NH3, NADH, and H+. Ultraviolet-visible light spectrophotometry (UV/Vis) was used at 340 nm to create a standard curve. This curve uses the Beer-Lambert Law to measure NADH concentration from absorbance. NADH is in a 1:1 ratio with each BCAA molecule thus relaying the content of the given sample. The assay is specific to the three BCAAs in their free form. Other amino acids, as well as BCAAs in oligopeptides, do not interfere with this experiment. Products including oligo- and polypeptides were not included for testing. The assay was performed for each product and ran against a known standard (≥98% L-leucine) for validation. Due to different supplements having different BCAA amounts per serving, % content of the claimed amount was measured. Results Compared to the amount provided by the labels of each supplement, BCAA content was on average only 61% of the manufacturer claims when compared to ≥98% L-leucine. This shows that these BCAA supplements do not meet label claims for BCAA content (P < 0.01). Conclusions The five tested nutritional supplements contain significantly less branched-chain amino acid content than claimed on the label. This experiment can be expanded on in the future to test content of other BCAA containing supplements to determine how common underdosing is in the industry as a whole. Funding Sources The author claims no funding sources.

scholarly journals Transcriptomic and metabolomic analysis reveals the role of CoA in the salt tolerance of Zygophyllum spp

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jie Wang ◽  
Xi Jiang ◽  
Chufeng Zhao ◽  
Zhongming Fang ◽  
Peipei Jiao
Keyword(s):  
Salt Stress ◽  
Salt Tolerance ◽  
Metabolomic Analysis ◽  
Kegg Pathways ◽  
Branched Chain Amino Acid ◽  
Significant Difference ◽  
Branched Chain ◽  
Shifting Sand ◽  
Important Medicinal Plant

Abstract Background Zygophyllum is an important medicinal plant, with notable properties such as resistance to salt, alkali, and drought, as well as tolerance of poor soils and shifting sand. However, the response mechanism of Zygophyllum spp. to abiotic stess were rarely studied. Results Here, we aimed to explore the salt-tolerance genes of Zygophyllum plants by transcriptomic and metabolic approaches. We chose Z. brachypterum, Z. obliquum and Z. fabago to screen for salt tolerant and sensitive species. Cytological observation showed that both the stem and leaf of Z. brachypterum were significantly thicker than those of Z. fabago. Then, we treated these three species with different concentrations of NaCl, and found that Z. brachypterum exhibited the highest salt tolerance (ST), while Z. fabago was the most sensitive to salt (SS). With the increase of salt concentration, the CAT, SOD and POD activity, as well as proline and chlorophyll content in SS decreased significantly more than in ST. After salt treatment, the proportion of open stomata in ST decreased significantly more than in SS, although there was no significant difference in stomatal number between the two species. Transcriptomic analysis identified a total of 11 overlapping differentially expressed genes (DEGs) in the leaves and roots of the ST and SS species after salt stress. Two branched-chain-amino-acid aminotransferase (BCAT) genes among the 11 DEGs, which were significantly enriched in pantothenate and CoA biosynthesis, as well as the valine, leucine and isoleucine biosynthesis pathways, were confirmed to be significantly induced by salt stress through qRT-PCR. Furthermore, overlapping differentially abundant metabolites showed that the pantothenate and CoA biosynthesis pathways were significantly enriched after salt stress, which was consistent with the KEGG pathways enriched according to transcriptomics. Conclusions In our study, transcriptomic and metabolomic analysis revealed that BCAT genes may affect the pantothenate and CoA biosynthesis pathway to regulate the salt tolerance of Zygophyllum species, which may constitute a newly identified signaling pathway through which plants respond to salt stress.

Ameliorative Potential of Glycyrrhiza glabra extracts on Memory Impairments in Stress Triggered Rats

2020 ◽  
Vol 06 ◽  
Author(s):  
Parul Kamboj ◽  
Ajit Kumar Thakur
Keyword(s):  
Antioxidant Enzyme ◽  
Learning And Memory ◽  
Acetylcholinesterase Activity ◽  
Molecular Study ◽  
Glycyrrhiza Glabra ◽  
Learning Ability ◽  
Future Research ◽  
Standard Drug ◽  
Behavioral Alteration ◽  
Memory Enhancing

Background: Glycyrrhiza glabra Linn. (Family: Fabaceae) has been known to very useful medicinal plant in the Traditional Medicinal Systems from the centuries. With ethnopharmacological values, it is well-reported plant for their traditional uses for anti-inflammatory, antioxidant, anxiolytic, expectorant activities, and antidepressant activities. Objective: Although it is described for memory enhancing activity, the present study was focused to examine the comparative effect of Glycyrrhiza glabra extracts viz. flavonoid rich (GGFE) and glycyrrhizin rich (GGGE) in stress triggered rats and to provide future research insight for this herbal drug, for which no scientific justification has been reported till now. Methods: Male Wister rats divided into 7 different groups (n= 6 per group) were given chronic foot-shock stress for 21 successive days with scheduled administration of the extracts (50 and 100 mg/kg) and standard drug (10 mg/kg) for 28 days. Elevated Plus Maze, Rectangular Maze, Morris Water Maze, and Locomotor activity were performed to test behavioral alteration and learning ability of stressed rats. Further, rats were sacrificed to assay acetylcholinesterase activity and antioxidant activity in brain samples for the mechanistic role in learning and memory. Results: Extracts of Glycyrrhiza glabra were indicated a significant alteration in stress induced learning and memory deficiency in behavioral parameters studied. These extracts were also modulated significant changes in acetylcholinesterase and antioxidant enzyme activity to improve the learning and memory of stressed rats. Conclusions: It is concluded that both extracts of Glycyrrhiza glabra (GGFE and GGGE) possess memory enhancing property in stress triggered rats. Moreover, these comparative results provided information and confirmed the high potential of GGGE in comparison to GGFE might be due to rich glycyrrhizin content present in GGGE responsible for acetylcholinesterase and antioxidant enzyme modulatory activity. Therefore, GGGE could be used as a promising lead for further mechanistic and molecular study for defining the role of glycyrrhizin of Glycyrrhiza glabra.

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