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mTOR & BCAA

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https://www.readbyqxmd.com/read/28336113/effect-of-branched-chain-amino-acid-ratio-on-the-proliferation-differentiation-and-expression-levels-of-key-regulators-involved-in-protein-metabolism-of-myocytes
#1
Yehui Duan, Liming Zeng, Fengna Li, Wenlong Wang, Yinghui Li, Qiuping Guo, Yujiao Ji, Bi'e Tan, Yulong Yin
OBJECTIVES: Branched-chain amino acids (BCAAs), including leucine (Leu), isoleucine (Ile), and valine (Val), are key regulators of protein synthesis in muscle. The aim of this study was to investigate the effect of different BCAA ratios (Leu:Ile:Val) on the proliferation, differentiation, and expression levels of the regulators related to protein metabolism of C2 C12 myocytes. METHODS: Studies were conducted in C2C12 myocytes exposed to different BCAA ratios (Leu: Ile: Val = 0, 1:0...
April 2017: Nutrition
https://www.readbyqxmd.com/read/28326005/bioactivity-of-food-peptides-biological-response-of-rats-to-bovine-milk-whey-peptides-following-acute-exercise
#2
Carolina Soares Moura, Pablo Christiano Barboza Lollo, Priscila Neder Morato, Eder Muller Risso, Jaime Amaya-Farfan
Background: Several physiologically beneficial effects of consuming a whey protein hydrolysate (WPH) have been attributed to the greater availability of bioactive peptides. Aims: The aim was to investigate the effect of four branched-chain amino acid- (BCAA-)containing dipeptides, present in WPH, on immune modulation, stimulation of HSP expression, muscle protein synthesis, glycogen content, satiety signals and the impact of these peptides on the plasma free amino acid profiles. Methods: The animals were divided in groups: control (rest, without gavage), vehicle (water), L-isoleucyl-L-leucine (lle-Leu), L-leucyl-L-isoleucine (Leu-lle), L-valyl-Lleucine (Val-Leu), L-leucyl-L-valine (Leu-Val) and WPH...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28235484/branched-chain-amino-acid-transaminase-1-bcat1-promotes-the-growth-of-breast-cancer-cells-through-improving-mtor-mediated-mitochondrial-biogenesis-and-function
#3
Ling Zhang, Junqing Han
Branched-chain amino acids (BCAAs) are important nutrient signals that have direct and indirect effects. BCAA catabolism is a conserved regulator of physiological aging and participates in diverse physiological and pathological processes, including carcinoma development. The roles of BCAA catabolism in human breast cancer remains unknown. Here we provide evidence that BCAA catabolism is involved in human breast cancer. The plasma and tissue levels of BCAAs are increased in breast cancer, which is accompanied by the elevated expression of the catabolic enzymes, including branched-chain amino acid transaminase 1 (BCAT1)...
February 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28127425/novel-metabolic-and-physiological-functions-of-branched-chain-amino-acids-a-review
#4
REVIEW
Shihai Zhang, Xiangfang Zeng, Man Ren, Xiangbing Mao, Shiyan Qiao
It is widely known that branched chain amino acids (BCAA) are not only elementary components for building muscle tissue but also participate in increasing protein synthesis in animals and humans. BCAA (isoleucine, leucine and valine) regulate many key signaling pathways, the most classic of which is the activation of the mTOR signaling pathway. This signaling pathway connects many diverse physiological and metabolic roles. Recent years have witnessed many striking developments in determining the novel functions of BCAA including: (1) Insufficient or excessive levels of BCAA in the diet enhances lipolysis...
2017: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/28089725/high-concentration-of-branched-chain-amino-acids-promotes-oxidative-stress-inflammation-and-migration-of-human-peripheral-blood-mononuclear-cells-via-mtorc1-activation
#5
Olha Zhenyukh, Esther Civantos, Marta Ruiz-Ortega, Maria Soledad Sánchez, Clotilde Vázquez, Concepción Peiró, Jesús Egido, Sebastián Mas
Leucine, isoleucine and valine are essential aminoacids termed branched-chain amino acids (BCAA) due to its aliphatic side-chain. In several pathological and physiological conditions increased BCAA plasma concentrations have been described. Elevated BCAA levels predict insulin resistance development. Moreover, BCAA levels higher than 2mmol/L are neurotoxic by inducing microglial activation in maple syrup urine disease. However, there are no studies about the direct effects of BCAA in circulating cells. We have explored whether BCAA could promote oxidative stress and pro-inflammatory status in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors...
March 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27886623/liver-bcatm-transgenic-mouse-model-reveals-the-important-role-of-the-liver-in-maintaining-bcaa-homeostasis
#6
Elitsa A Ananieva, Cynthia G Van Horn, Meghan R Jones, Susan M Hutson
Unlike other amino acids, the branched-chain amino acids (BCAAs) largely bypass first-pass liver degradation due to a lack of hepatocyte expression of the mitochondrial branched-chain aminotransferase (BCATm). This sets up interorgan shuttling of BCAAs and liver-skeletal muscle cooperation in BCAA catabolism. To explore whether complete liver catabolism of BCAAs may impact BCAA shuttling in peripheral tissues, the BCATm gene was stably introduced into mouse liver. Two transgenic mouse lines with low and high hepatocyte expression of the BCATm transgene (LivTg-LE and LivTg-HE) were created and used to measure liver and plasma amino acid concentrations and determine whether the first two BCAA enzymatic steps in liver, skeletal muscle, heart and kidney were impacted...
February 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27843095/branched-chain-amino-acids-cause-liver-injury-in-obese-diabetic-mice-by-promoting-adipocyte-lipolysis-and-inhibiting-hepatic-autophagy
#7
Fuyang Zhang, Shihao Zhao, Wenjun Yan, Yunlong Xia, Xiyao Chen, Wei Wang, Jinglong Zhang, Chao Gao, Cheng Peng, Feng Yan, Huishou Zhao, Kun Lian, Yan Lee, Ling Zhang, Wayne Bond Lau, Xinliang Ma, Ling Tao
The Western meat-rich diet is both high in protein and fat. Although the hazardous effect of a high fat diet (HFD) upon liver structure and function is well recognized, whether the co-presence of high protein intake contributes to, or protects against, HF-induced hepatic injury remains unclear. Increased intake of branched chain amino acids (BCAA, essential amino acids compromising 20% of total protein intake) reduces body weight. However, elevated circulating BCAA is associated with non-alcoholic fatty liver disease and injury...
November 2016: EBioMedicine
https://www.readbyqxmd.com/read/27542406/defective-branched-chain-amino-acids-catabolism-contributes-to-cardiac-dysfunction-and-remodeling-following-myocardial-infarction
#8
Wei Wang, Fuyang Zhang, Yunlong Xia, Shihao Zhao, Wenjuan Yan, Helin Wang, Yan Lee, Congye Li, Ling Zhang, Kun Lian, Erhe Gao, Hexiang Cheng, Ling Tao
Cardiac metabolic remodeling is a central event during heart failure (HF) development following myocardial infarction (MI). It is well-known that myocardial glucose and fatty acids dysmetabolism contributes to post-MI cardiac dysfunction and remodeling. However, the role of amino acids metabolism in post-MI HF remains elusive. Branched chain amino acids (BCAA) are an important group of essential amino acids and function as a crucial nutrient signaling in mammalian animals. The present study aimed to determine the role of cardiac BCAA metabolism in post-MI HF progression...
August 19, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27490818/branched-chain-amino-acids-as-new-biomarkers-of-major-depression-a-novel-neurobiology-of-mood-disorder
#9
Andreas Baranyi, Omid Amouzadeh-Ghadikolai, Dirk von Lewinski, Hans-Bernd Rothenhäusler, Simon Theokas, Christoph Robier, Harald Mangge, Gerhard Reicht, Peter Hlade, Andreas Meinitzer
BACKGROUND: The proteinogenic branched-chain amino acids (BCAAs) valine, leucine and isoleucine might play an unrecognised crucial role in the development of depression through their activation of the mammalian target of rapamycin (mTor) pathway. The aim of this research project is to evaluate whether BCAAs are altered in patients with major depression and might thus be appropriate biomarkers for major depression. METHODS: The concentrations of valine, leucine and isoleucine were determined in 71 in-patients with major depression and 48 healthy controls by high-pressure liquid chromatography...
2016: PloS One
https://www.readbyqxmd.com/read/27376324/the-emerging-role-of-branched-chain-amino-acids-in-insulin-resistance-and-metabolism
#10
REVIEW
Mee-Sup Yoon
Insulin is required for maintenance of glucose homeostasis. Despite the importance of insulin sensitivity to metabolic health, the mechanisms that induce insulin resistance remain unclear. Branched-chain amino acids (BCAAs) belong to the essential amino acids, which are both direct and indirect nutrient signals. Even though BCAAs have been reported to improve metabolic health, an increased BCAA plasma level is associated with a high risk of metabolic disorder and future insulin resistance, or type 2 diabetes mellitus (T2DM)...
July 1, 2016: Nutrients
https://www.readbyqxmd.com/read/27259235/germline-brca1-mutation-reprograms-breast-epithelial-cell-metabolism-towards-mitochondrial-dependent-biosynthesis-evidence-for-metformin-based-starvation-strategies-in-brca1-carriers
#11
Elisabet Cuyàs, Salvador Fernández-Arroyo, Tomás Alarcón, Ruth Lupu, Jorge Joven, Javier A Menendez
We hypothesized that women inheriting one germline mutation of the BRCA1 gene ("one-hit") undergo cell-type-specific metabolic reprogramming that supports the high biosynthetic requirements of breast epithelial cells to progress to a fully malignant phenotype. Targeted metabolomic analysis was performed in isogenic pairs of nontumorigenic human breast epithelial cells in which the knock-in of 185delAG mutation in a single BRCA1 allele leads to genomic instability. Mutant BRCA1 one-hit epithelial cells displayed constitutively enhanced activation of biosynthetic nodes within mitochondria...
August 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27079773/supplementation-of-branched-chain-amino-acids-to-a-reduced-protein-diet-improves-growth-performance-in-piglets-involvement-of-increased-feed-intake-and-direct-muscle-growth-promoting-effect
#12
Liufeng Zheng, Hongkui Wei, Chuanshang Cheng, Quanhang Xiang, Jiaman Pang, Jian Peng
The aim of this study was to investigate whether supplementing branched-chain amino acids (AA) (BCAA) along with a reduced-protein diet increases piglet growth, and whether elevated feed intake and muscle growth-promoting effect contribute to this improvement. In Expt 1, twenty-eight weanling piglets were randomly fed one of the following four diets: a positive control (PC) diet, a reduced-protein negative control (NC) diet, an NC diet supplemented with BCAA to the same levels as in the PC diet (test 1 (T1)) and an NC diet supplemented with a 2-fold dose of BCAA in T1 diet (test 2 (T2)) for 28 d...
June 2016: British Journal of Nutrition
https://www.readbyqxmd.com/read/26957625/impact-of-dietary-branched-chain-amino-acids-concentration-on-broiler-chicks-during-aflatoxicosis
#13
X Chen, Q Zhang, T J Applegate
A 20-day trial was conducted to determine the effects of dietary branched-chain amino acids (BCAA) on performance, nutrient digestibility, and gene expression of the mTOR pathway in broiler chicks when exposed to aflatoxin B1 (AFB1). The 6 dietary treatments were arranged in a 2 × 3 factorial with 3 BCAA concentrations (1.16, 1.94, and 2.73%) with or without 1.5 mg/kg AFB1 (1.77 mg/kg analyzed). Each diet was fed to 8 replicate cages (6 chicks per cage) from 6 to 20 d of age. Exposure to AFB1 significantly reduced gain:feed ratio and breast muscle weight (P < 0...
June 1, 2016: Poultry Science
https://www.readbyqxmd.com/read/26620638/branched-chain-amino-acid-catabolism-is-a-conserved-regulator-of-physiological-ageing
#14
Johannes Mansfeld, Nadine Urban, Steffen Priebe, Marco Groth, Christiane Frahm, Nils Hartmann, Juliane Gebauer, Meenakshi Ravichandran, Anne Dommaschk, Sebastian Schmeisser, Doreen Kuhlow, Shamci Monajembashi, Sibylle Bremer-Streck, Peter Hemmerich, Michael Kiehntopf, Nicola Zamboni, Christoph Englert, Reinhard Guthke, Christoph Kaleta, Matthias Platzer, Jürgen Sühnel, Otto W Witte, Kim Zarse, Michael Ristow
Ageing has been defined as a global decline in physiological function depending on both environmental and genetic factors. Here we identify gene transcripts that are similarly regulated during physiological ageing in nematodes, zebrafish and mice. We observe the strongest extension of lifespan when impairing expression of the branched-chain amino acid transferase-1 (bcat-1) gene in C. elegans, which leads to excessive levels of branched-chain amino acids (BCAAs). We further show that BCAAs reduce a LET-363/mTOR-dependent neuro-endocrine signal, which we identify as DAF-7/TGFβ, and that impacts lifespan depending on its related receptors, DAF-1 and DAF-4, as well as ultimately on DAF-16/FoxO and HSF-1 in a cell-non-autonomous manner...
2015: Nature Communications
https://www.readbyqxmd.com/read/26351290/global-deletion-of-bcatm-increases-expression-of-skeletal-muscle-genes-associated-with-protein-turnover
#15
Christopher J Lynch, Scot R Kimball, Yuping Xu, Anna C Salzberg, Yuka Imamura Kawasawa
Consumption of a protein-containing meal by a fasted animal promotes protein accretion in skeletal muscle, in part through leucine stimulation of protein synthesis and indirectly through repression of protein degradation mediated by its metabolite, α-ketoisocaproate. Mice lacking the mitochondrial branched-chain aminotransferase (BCATm/Bcat2), which interconverts leucine and α-ketoisocaproate, exhibit elevated protein turnover. Here, the transcriptomes of gastrocnemius muscle from BCATm knockout (KO) and wild-type mice were compared by next-generation RNA sequencing (RNA-Seq) to identify potential adaptations associated with their persistently altered nutrient signaling...
November 2015: Physiological Genomics
https://www.readbyqxmd.com/read/26255285/the-role-of-leucine-and-its-metabolites-in-protein-and-energy-metabolism
#16
REVIEW
Yehui Duan, Fengna Li, Yinghui Li, Yulong Tang, Xiangfeng Kong, Zemeng Feng, Tracy G Anthony, Malcolm Watford, Yongqing Hou, Guoyao Wu, Yulong Yin
Leucine (Leu) is a nutritionally essential branched-chain amino acid (BCAA) in animal nutrition. It is usually one of the most abundant amino acids in high-quality protein foods. Leu increases protein synthesis through activation of the mammalian target of rapamycin (mTOR) signaling pathway in skeletal muscle, adipose tissue and placental cells. Leu promotes energy metabolism (glucose uptake, mitochondrial biogenesis, and fatty acid oxidation) to provide energy for protein synthesis, while inhibiting protein degradation...
January 2016: Amino Acids
https://www.readbyqxmd.com/read/26226162/administration-of-exogenous-growth-hormone-is-associated-with-changes-in-plasma-and-intracellular-mammary-amino-acid-profiles-and-abundance-of-the-mammary-gland-amino-acid-transporter-slc3a2-in-mid-lactation-dairy-cows
#17
Quentin L Sciascia, David Pacheco, Susan A McCoard
The objectives of this study were to (1) identify changes in plasma and mammary intracellular amino acid (AA) profiles in dairy cows treated with growth hormone (GH), and (2) evaluate the expression of mammary gland genes involved in the transport of AA identified in (1). Eight non-pregnant (n = 4 per group) lactating dairy cows were treated with a single subcutaneous injection of either a slow-release formulation of commercially available GH (Lactotropin 500 mg) or physiological saline solution. Six days after treatment, cows were milked and blood collected from the jugular vein for the analysis of free AA in the plasma...
2015: PloS One
https://www.readbyqxmd.com/read/26086773/dexamethasone-and-bcaa-failed-to-modulate-muscle-mass-and-mtor-signaling-in-gh-deficient-rats
#18
Hikaru Nishida, Ayaka Ikegami, Chiaki Kaneko, Hitomi Kakuma, Hisano Nishi, Noriko Tanaka, Michiko Aoyama, Makoto Usami, Yasuhiko Okimura
Branched-chain amino acids (BCAAs) and IGF-I, the secretion of which is stimulated by growth hormone (GH), prevent muscle atrophy. mTOR plays a pivotal role in the protective actions of BCAA and IGF-1. The pathway by which BCAA activates mTOR is different from that of IGF-1, which suggests that BCAA and GH work independently. We tried to examine whether BCAA exerts a protective effect against dexamethasone (Dex)-induced muscle atrophy independently of GH using GH-deficient spontaneous dwarf rats (SDRs). Unexpectedly, Dex did not induce muscle atrophy assessed by the measurement of cross-sectional area (CSA) of the muscle fibers and did not increase atrogin-1, MuRF1 and REDD1 expressions, which are activated during protein degradation...
2015: PloS One
https://www.readbyqxmd.com/read/26030804/gc-ms-based-plasma-metabolomics-for-identification-of-candidate-biomarkers-for-hepatocellular-carcinoma-in-egyptian-cohort
#19
Mohammad R Nezami Ranjbar, Yue Luo, Cristina Di Poto, Rency S Varghese, Alessia Ferrarini, Chi Zhang, Naglaa I Sarhan, Hanan Soliman, Mahlet G Tadesse, Dina H Ziada, Rabindra Roy, Habtom W Ressom
This study evaluates changes in metabolite levels in hepatocellular carcinoma (HCC) cases vs. patients with liver cirrhosis by analysis of human blood plasma using gas chromatography coupled with mass spectrometry (GC-MS). Untargeted metabolomic analysis of plasma samples from participants recruited in Egypt was performed using two GC-MS platforms: a GC coupled to single quadruple mass spectrometer (GC-qMS) and a GC coupled to a time-of-flight mass spectrometer (GC-TOFMS). Analytes that showed statistically significant changes in ion intensities were selected using ANOVA models...
2015: PloS One
https://www.readbyqxmd.com/read/26020623/maternal-diabetes-leads-to-adaptation-in-embryonic-amino-acid-metabolism-during-early-pregnancy
#20
Jacqueline Gürke, Frank Hirche, René Thieme, Elisa Haucke, Maria Schindler, Gabriele I Stangl, Bernd Fischer, Anne Navarrete Santos
During pregnancy an adequate amino acid supply is essential for embryo development and fetal growth. We have studied amino acid composition and branched chain amino acid (BCAA) metabolism at day 6 p.c. in diabetic rabbits and blastocysts. In the plasma of diabetic rabbits the concentrations of 12 amino acids were altered in comparison to the controls. Notably, the concentrations of the BCAA leucine, isoleucine and valine were approximately three-fold higher in diabetic rabbits than in the control. In the cavity fluid of blastocysts from diabetic rabbits BCAA concentrations were twice as high as those from controls, indicating a close link between maternal diabetes and embryonic BCAA metabolism...
2015: PloS One
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