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mTOR AND BCAA

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https://www.readbyqxmd.com/read/27886623/liver-bcatm-transgenic-mouse-model-reveals-the-important-role-of-the-liver-in-maintaining-bcaa-homeostasis
#1
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...
November 2, 2016: 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
#2
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...
October 11, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27542406/defective-branched-chain-amino-acids-catabolism-contributes-to-cardiac-dysfunction-and-remodeling-following-myocardial-infarction
#3
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
#4
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
#5
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)...
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
#6
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...
May 31, 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
#7
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
#8
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
#9
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/26255285/the-role-of-leucine-and-its-metabolites-in-protein-and-energy-metabolism
#10
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
#11
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/26120590/nutrient-excess-in-ampk-downregulation-and-insulin-resistance
#12
Kimberly A Coughlan, Rudy J Valentine, Neil B Ruderman, Asish K Saha
It is well established that chronic exposure to excess nutrients leads to insulin resistance (IR) in skeletal muscle. Since skeletal muscle is responsible for 70-80% of insulin-stimulated glucose uptake, skeletal muscle IR is a key pathological component of type 2 diabetes (T2D). Recent evidence suggests that inhibition of the nutrient-sensing enzyme AMP-activated protein kinase (AMPK) is an early event in the development of IR in response to high glucose, branched chain amino acids (BCAA), or fatty acids (FA)...
July 2013: Journal of Endocrinology, Diabetes & Obesity
https://www.readbyqxmd.com/read/26086773/dexamethasone-and-bcaa-failed-to-modulate-muscle-mass-and-mtor-signaling-in-gh-deficient-rats
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/25787688/branched-chain-amino-acids-modulate-the-expression-of-hepatic-fatty-acid-metabolism-related-genes-in-female-broiler-chickens
#16
Jie Bai, Elizabeth Greene, Weifen Li, Michael T Kidd, Sami Dridi
SCOPE: The effects and roles of branched-chain amino acids (BCAAs) in hepatic fat metabolism are still unknown. METHODS AND RESULTS: Here, we used broiler chickens, in which lipogenesis occurs essentially in the liver as in human, to investigate the effects of three levels of BCAAs (control "C," low "L" and exogenous supplemented diet "L+S") on growth, carcass traits, immunity, and hepatic fat metabolism. Despite the same productive performance, immunity, and plasma BCAA levels between all groups, low BCAA levels significantly downregulated the hepatic expression of lipogenic genes particularly acetyl-CoA carboxylase alpha (ACCα) and stearoyl-coA desaturase 1 (p = 0...
June 2015: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/25721400/chronic-activation-of-mtor-complex-1-by-branched-chain-amino-acids-and-organ-hypertrophy
#17
S Hallaj Neishabouri, S M Hutson, J Davoodi
The mitochondrial branched chain aminotransferase-deficient mouse model (BCATm KO), which exhibits elevated plasma and tissue branched chain amino acids (BCAAs), was used to study the effect of BCAAs on mammalian target of rapamycin complex 1 (mTORC1) regulation of organ size. BCATm is the first enzyme in the BCAA catabolic pathway. BCATm KO mouse exhibited hypertrophy of heart, kidneys, and spleen. On the other hand, the mass of the gastrocnemius was reduced relative to body mass. Feeding the mice with a diet supplemented with rapamycin prevented the enlargement of the heart and spleen, suggesting that mTORC1 is the mediator of these effects...
June 2015: Amino Acids
https://www.readbyqxmd.com/read/25613922/metabolic-and-molecular-responses-to-leucine-enriched-branched-chain-amino-acid-supplementation-in-the-skeletal-muscle-of-alcoholic-cirrhosis
#18
Cynthia Tsien, Gangarao Davuluri, Dharmvir Singh, Allawy Allawy, Gabriella A M Ten Have, Samjhana Thapaliya, John M Schulze, David Barnes, Arthur J McCullough, Marielle P K J Engelen, Nicolaas E P Deutz, Srinivasan Dasarathy
UNLABELLED: Skeletal muscle loss (sarcopenia) is a major clinical complication in alcoholic cirrhosis with no effective therapy. Skeletal muscle autophagic proteolysis and myostatin expression (inhibitor of protein synthesis) are increased in cirrhosis and believed to contribute to anabolic resistance. A prospective study was performed to determine the mechanisms of sarcopenia in alcoholic cirrhosis and potential reversal by leucine. In six well-compensated, stable, alcoholic patients with cirrhosis and eight controls, serial vastus lateralis muscle biopsies were obtained before and 7 hours after a single oral branched chain amino acid mixture enriched with leucine (BCAA/LEU)...
June 2015: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/25553480/nutritional-and-regulatory-roles-of-leucine-in-muscle-growth-and-fat-reduction
#19
REVIEW
Yehui Duan, Fengna Li, Hongnan Liu, Yinghui Li, Yingying Liu, Xiangfeng Kong, Yuzhe Zhang, Dun Deng, Yulong Tang, Zemeng Feng, Guoyao Wu, Yulong Yin
The metabolic roles for L-leucine, an essential branched-chain amino acid (BCAA), go far beyond serving exclusively as a building block for de novo protein synthesis. Growing evidence shows that leucine regulates protein and lipid metabolism in animals. Specifically, leucine activates the mammalian target of rapamycin (mTOR) signaling pathway, including the 70 kDa ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein 1 (4EBP1) to stimulate protein synthesis in skeletal muscle and adipose tissue and to promote mitochondrial biogenesis, resulting in enhanced cellular respiration and energy partitioning...
2015: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/24685128/leucine-supplementation-differentially-enhances-pancreatic-cancer-growth-in-lean-and-overweight-mice
#20
Kristyn A Liu, Laura M Lashinger, Audrey J Rasmussen, Stephen D Hursting
BACKGROUND: The risk of pancreatic cancer, the 4th deadliest cancer for both men and women in the United States, is increased by obesity. Calorie restriction (CR) is a well-known dietary regimen that prevents or reverses obesity and suppresses tumorigenesis in a variety of animal models, at least in part via inhibition of mammalian target of rapamycin (mTOR) signaling. Branched-chain amino acids (BCAA), especially leucine, activate mTOR and enhance growth and proliferation of myocytes and epithelial cells, which is why leucine is a popular supplement among athletes...
2014: Cancer & Metabolism
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