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https://www.readbyqxmd.com/read/29144447/bcat1-restricts-%C3%AE-kg-levels-in-aml-stem-cells-leading-to-idhmut-like-dna-hypermethylation
#1
Simon Raffel, Mattia Falcone, Niclas Kneisel, Jenny Hansson, Wei Wang, Christoph Lutz, Lars Bullinger, Gernot Poschet, Yannic Nonnenmacher, Andrea Barnert, Carsten Bahr, Petra Zeisberger, Adriana Przybylla, Markus Sohn, Martje Tönjes, Ayelet Erez, Lital Adler, Patrizia Jensen, Claudia Scholl, Stefan Fröhling, Sibylle Cocciardi, Patrick Wuchter, Christian Thiede, Anne Flörcken, Jörg Westermann, Gerhard Ehninger, Peter Lichter, Karsten Hiller, Rüdiger Hell, Carl Herrmann, Anthony D Ho, Jeroen Krijgsveld, Bernhard Radlwimmer, Andreas Trumpp
The branched-chain amino acid (BCAA) pathway and high levels of BCAA transaminase 1 (BCAT1) have recently been associated with aggressiveness in several cancer entities. However, the mechanistic role of BCAT1 in this process remains largely uncertain. Here, by performing high-resolution proteomic analysis of human acute myeloid leukaemia (AML) stem-cell and non-stem-cell populations, we find the BCAA pathway enriched and BCAT1 protein and transcripts overexpressed in leukaemia stem cells. We show that BCAT1, which transfers α-amino groups from BCAAs to α-ketoglutarate (αKG), is a critical regulator of intracellular αKG homeostasis...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29141216/slc3a2-mediates-branched-chain-amino-acid-dependent-maintenance-of-regulatory-t-cells
#2
Kayo Ikeda, Makoto Kinoshita, Hisako Kayama, Shushi Nagamori, Pornparn Kongpracha, Eiji Umemoto, Ryu Okumura, Takashi Kurakawa, Mari Murakami, Norihisa Mikami, Yasunori Shintani, Satoko Ueno, Ayatoshi Andou, Morihiro Ito, Hideki Tsumura, Koji Yasutomo, Keiichi Ozono, Seiji Takashima, Shimon Sakaguchi, Yoshikatsu Kanai, Kiyoshi Takeda
Foxp3(+) regulatory T (Treg) cells, which suppress immune responses, are highly proliferative in vivo. However, it remains unclear how the active replication of Treg cells is maintained in vivo. Here, we show that branched-chain amino acids (BCAAs), including isoleucine, are required for maintenance of the proliferative state of Treg cells via the amino acid transporter Slc3a2-dependent metabolic reprogramming. Mice fed BCAA-reduced diets showed decreased numbers of Foxp3(+) Treg cells with defective in vivo proliferative capacity...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29122443/identification-of-serum-metabolites-associated-with-obesity-and-traditional-risk-factors-for-metabolic-disease-in-chinese-adults
#3
S M Wang, R Y Yang, M Wang, F S Ji, H X Li, Y M Tang, W X Chen, J Dong
BACKGROUND AND AIMS: Obesity is a major worldwide health problem and is often associated with many metabolic diseases. Levels of several serum-specific metabolites may be altered in patients with these metabolic diseases. We aimed to investigate the associations of serum metabolite levels with obesity and traditional risk factors for metabolic disease in Chinese individuals. METHODS AND RESULTS: Six-hundred Chinese individuals undergoing annual physical exams were recruited and categorized into overweight/obese and control groups (1:1 ratio)...
October 3, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/29118722/branched-chain-amino-acid-negatively-regulates-klf15-expression-via-pi3k-akt-pathway
#4
Yunxia Liu, Weibing Dong, Jing Shao, Yibin Wang, Meiyi Zhou, Haipeng Sun
Recent studies have linked branched-chain amino acid (BCAA) with numerous metabolic diseases. However, the molecular basis of BCAA's roles in metabolic regulation remains to be established. KLF15 (Krüppel-like factor 15) is a transcription factor and master regulator of glycemic, lipid, and amino acids metabolism. In the present study, we found high concentrations of BCAA suppressed KLF15 expression while BCAA starvation induced KLF15 expression, suggesting KLF15 expression is negatively controlled by BCAA...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29108327/evaluation-of-the-branched-chain-amino-acid-to-tyrosine-ratio-prior-to-treatment-as-a-prognostic-predictor-in-patients-with-liver-cirrhosis
#5
Toru Ishikawa, Michitaka Imai, Masayoshi Ko, Hiroki Sato, Yujiro Nozawa, Tomoe Sano, Akito Iwanaga, Keiichi Seki, Terasu Honma, Toshiaki Yoshida
This study evaluated whether the branched-chain amino acid-to-tyrosine ratio (BTR) is a prognostic predictive factor in patients with liver cirrhosis by determining the relationship of the BTR with event-free survival in a retrospective, observational cohort study. The medical records of patients with liver cirrhosis who visited our institution from February 2000 to May 2012 were examined. Events due to liver cirrhosis were defined as death, worsening of esophageal and/or gastric varices, hepatocellular carcinoma, and liver failure...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29104034/distribution-of-the-branched-chain-%C3%AE-ketoacid-dehydrogenase-complex-e1%C3%AE-subunit-and-glutamate-dehydrogenase-in-the-human-brain-and-their-role-in-neuro-metabolism
#6
Jonathon Hull, Marcela Usmari Moraes, Emma Brookes, Seth Love, Myra E Conway
Glutamate is the major excitatory neurotransmitter of the central nervous system, with the branched-chain amino acids (BCAAs) acting as key nitrogen donors for de novo glutamate synthesis. Despite the importance of these major metabolites, their metabolic pathway in the human brain is still not well characterised. The metabolic pathways that influence the metabolism of BCAAs have been well characterised in rat models. However, the expression of key proteins such as the branched-chain α-ketoacid dehydrogenase (BCKD) complex and glutamate dehydrogenase isozymes (GDH) in the human brain is still not well characterised...
November 9, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29075976/specific-plasma-amino-acid-disturbances-associated-with-metabolic-syndrome
#7
Marta Siomkajło, Jacek Rybka, Magdalena Mierzchała-Pasierb, Andrzej Gamian, Joanna Stankiewicz-Olczyk, Marek Bolanowski, Jacek Daroszewski
PURPOSE: The primary objective of the present study was to examine the association between branched chain and aromatic amino acid profiles (BCAA and AAA respectively) and the metabolic syndrome (MS), and to evaluate the clinical utility of these associations in the diagnostic process. METHODS: Two hundred and sixty three healthy men with MS [MS(+): n = 165] and without MS [MS(-): n = 98] were enrolled in the observational study. Anthropometrical, biochemical, and amino acid measurements were performed...
October 26, 2017: Endocrine
https://www.readbyqxmd.com/read/29075574/perinatal-western-type-diet-and-associated-gestational-weight-gain-alter-postpartum-maternal-mood
#8
Jessica L Bolton, Melanie G Wiley, Bailey Ryan, Samantha Truong, Melva Strait, Dana Creighton Baker, Nancy Y Yang, Olga Ilkayeva, Thomas M O'Connell, Shelley W Wroth, Cristina L Sánchez, Geeta Swamy, Christopher Newgard, Cynthia Kuhn, Staci D Bilbo, Leigh Ann Simmons
INTRODUCTION: The role of perinatal diet in postpartum maternal mood disorders, including depression and anxiety, remains unclear. We investigated whether perinatal consumption of a Western-type diet (high in fat and branched-chain amino acids [BCAA]) and associated gestational weight gain (GWG) cause serotonin dysregulation in the central nervous system (CNS), resulting in postpartum depression and anxiety (PPD/A). METHODS: Mouse dams were fed one of four diets (high-fat/high BCAA, low-fat/high BCAA, high-fat, and low-fat) prior to mating and throughout gestation and lactation...
October 2017: Brain and Behavior
https://www.readbyqxmd.com/read/29066459/branched-chain-ketoacids-secreted-by-glioblastoma-cells-via-mct1-modulate-macrophage-phenotype
#9
Lidia Santos Silva, Gernot Poschet, Yannic Nonnenmacher, Holger M Becker, Sean Sapcariu, Ann-Christin Gaupel, Magdalena Schlotter, Yonghe Wu, Niclas Kneisel, Martina Seiffert, Rüdiger Hell, Karsten Hiller, Peter Lichter, Bernhard Radlwimmer
Elevated amino acid catabolism is common to many cancers. Here, we show that glioblastoma are excreting large amounts of branched-chain ketoacids (BCKAs), metabolites of branched-chain amino acid (BCAA) catabolism. We show that efflux of BCKAs, as well as pyruvate, is mediated by the monocarboxylate transporter 1 (MCT1) in glioblastoma. MCT1 locates in close proximity to BCKA-generating branched-chain amino acid transaminase 1, suggesting possible functional interaction of the proteins. Using in vitro models, we demonstrate that tumor-excreted BCKAs can be taken up and re-aminated to BCAAs by tumor-associated macrophages...
October 24, 2017: EMBO Reports
https://www.readbyqxmd.com/read/29062026/early-onset-and-classical-forms-of-type-2-diabetes-show-impaired-expression-of-genes-involved-in-muscle-branched-chain-amino-acids-metabolism
#10
María Isabel Hernández-Alvarez, Angels Díaz-Ramos, María Berdasco, Jeff Cobb, Evarist Planet, Diane Cooper, Agnieszka Pazderska, Krzystof Wanic, Declan O'Hanlon, Antonio Gomez, Laura R de la Ballina, Manel Esteller, Manuel Palacin, Donal J O'Gorman, John J Nolan, Antonio Zorzano
The molecular mechanisms responsible for the pathophysiological traits of type 2 diabetes are incompletely understood. Here we have performed transcriptomic analysis in skeletal muscle, and plasma metabolomics from subjects with classical and early-onset forms of type 2 diabetes (T2D). Focused studies were also performed in tissues from ob/ob and db/db mice. We document that T2D, both early and late onset, are characterized by reduced muscle expression of genes involved in branched-chain amino acids (BCAA) metabolism...
October 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29048482/n-acetylglucosamine-more-than-a-silent-partner-in-insulin-resistance
#11
Geoffrey G Hesketh, James W Dennis
Pedersen et al. (Pedersen HK, Gudmundsdottir V, Nielsen HB, Hyotylainen T, Nielsen T, Jensen BA, Forslund K, Hildebrand F, Prifti E, Falony G, et al. 2016. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature. 535: 376-381.) report that human serum levels of branched-chain amino acids (BCAA) and N-acetylglucosamine (GlcNAc) increase in proportion to insulin resistance. They focus on the microbiome and the contributing subset of microbe species, thereby demonstrating disease causality in mice...
July 1, 2017: Glycobiology
https://www.readbyqxmd.com/read/29046328/genetic-support-for-a-causal-role-of-insulin-resistance-on-circulating-branched-chain-amino-acids-and-inflammation
#12
Qin Wang, Michael V Holmes, George Davey Smith, Mika Ala-Korpela
OBJECTIVE: Insulin resistance has deleterious effects on cardiometabolic disease. We used Mendelian randomization analyses to clarify the causal relationships of insulin resistance (IR) on circulating blood-based metabolites to shed light on potential mediators of the IR to cardiometabolic disease relationship. RESEARCH DESIGN AND METHODS: We used 53 single nucleotide polymorphisms associated with IR from a recent genome-wide association study (GWAS) to explore their effects on circulating lipids and metabolites...
October 18, 2017: Diabetes Care
https://www.readbyqxmd.com/read/29046316/evidence-for-the-presence-in-rainbow-trout-brain-of-amino-acid-sensing-systems-involved-in-the-control-of-food-intake
#13
Sara Comesana, Cristina Velasco, Rosa M Ceinos, Marcos A Lopez-Patiño, Jesus M Miguez, Sofia Morais, Jose L Soengas
To assess the existence of central amino acid sensing systems in fish we carried out two experiments in rainbow trout. In the first one, we injected ICV two different branched-chain amino acids (BCAA), leucine and valine, and assessed food intake up to 48 h later. Leucine decreased and valine increased food intake. In a second experiment, 6h after similar ICV treatment we determined changes in parameters related to putative amino acid sensing systems. Amino acid sensing systems respond to leucine in hypothalamus and telencephalon, and to valine in telencephalon...
October 18, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29037781/uncovering-the-role-of-branched-chain-amino-acid-transaminases-in-saccharomyces-cerevisiae-isobutanol-biosynthesis
#14
Sarah K Hammer, José L Avalos
Isobutanol and other branched-chain higher alcohols (BCHAs) are promising advanced biofuels derived from the degradation of branched-chain amino acids (BCAAs). The yeast Saccharomyces cerevisiae is a particularly attractive host for the production of BCHAs due to its high tolerance to alcohols and prevalent use in the bioethanol industry. Degradation of BCAAs begins with transamination reactions, catalyzed by branched-chain amino acid transaminases (BCATs) located in the mitochondria (Bat1p) and cytosol (Bat2p)...
October 13, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/29035970/emerging-perspectives-on-branched-chain-amino-acid-metabolism-during-adipocyte-differentiation
#15
Daniela Salinas-Rubio, Armando R Tovar, Lilia G Noriega
PURPOSE OF REVIEW: Adipogenesis has been extensively studied in the context of carbohydrate and lipid metabolism. However, little information exists on the role of amino acid metabolism during adipocyte differentiation. Here, we review how branched-chain amino acid (BCAA) metabolism is modified during adipogenesis and, due to the limited information in the area, address questions that remain to be answered with further research. RECENT FINDINGS: BCAAs are rapidly consumed during adipocyte differentiation and are indispensable for this process...
October 14, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/29035969/effects-of-medical-food-leucine-content-in-the-management-of-methylmalonic-and-propionic-acidemias
#16
Jennifer G Myles, Irini Manoli, Charles P Venditti
PURPOSE OF REVIEW: The current review highlights the varied effects of medical foods high in leucine (Leu) and devoid of valine (Val) and isoleucine (Ile) in the management of methylmalonic acidemia (MMA) and propionic acidemia and cobalamin C (cblC) deficiency, aiming to advance dietary practices. RECENT FINDINGS: Leu is a key metabolic regulator with a multitude of effects on different organ systems. Recent observational studies have demonstrated that these effects can have unintended consequences in patients with MMA as a result of liberal use of medical foods...
October 14, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/29030588/impaired-branched-chain-amino-acid-metabolism-may-underlie-the-nonalcoholic-fatty-liver-disease-like-pathology-of-neonatal-testosterone-treated-female-rats
#17
Álvaro Anzai, Rodrigo R Marcondes, Thiago H Gonçalves, Kátia C Carvalho, Manuel J Simões, Natália Garcia, José M Soares, Vasantha Padmanabhan, Edmund C Baracat, Ismael D C G da Silva, Gustavo A R Maciel
Polycystic ovary syndrome (PCOS) is frequently associated with non-alcoholic fatty liver disease (NAFLD), but the mechanisms involved in the development of NAFLD in PCOS are not well known. We investigated histological changes and metabolomic profile in the liver of rat models of PCOS phenotype induced by testosterone or estradiol. Two-day old female rats received sc injections of 1.25 mg testosterone propionate (Testos; n = 10), 0.5 mg estradiol benzoate (E2; n = 10), or vehicle (control group, CNT; n = 10)...
October 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29024598/effects-of-long-term-exposures-to-low-iron-and-branched-chain-amino-acid-containing-diets-on-aging-skeletal-muscle-of-fisher-344-brown-norway-rats
#18
Yuho Kim, Sok Sambo Men, Chen Liang, Candace N Receno, Tom D Brutsaert, Donna L Korol, Kevin S Heffernan, Keith C DeRuisseau
Aging skeletal muscle displays an altered iron status that may promote oxidative stress and sarcopenia. A low iron (LI) containing diet could reduce muscle iron status and attenuate age-related muscle atrophy. Supplemental branched-chain amino acids (BCAA) may also alleviate sarcopenia by promoting muscle protein synthesis and iron status improvement. This study examined individual and combined effects of LI and BCAA diets on anabolic signaling and iron status in skeletal muscle of aging rats. Twenty-nine-month-old male F344BN rats consumed the following control-base diets: Control + regular iron (35 mg iron/kg) (CR; n = 11); Control + LI (~6 mg iron/kg) (CL; n = 11); 2×BCAA + regular iron (BR; n = 10); and 2×BCAA + LI (BL; n = 12) for 12 weeks...
October 12, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/29016470/efficacy-of-branched-chain-amino-acid-supplementation-and-walking-exercise-for-preventing-sarcopenia-in-patients-with-liver-cirrhosis
#19
Atsushi Hiraoka, Kojiro Michitaka, Daisuke Kiguchi, Hirofumi Izumoto, Hidetaro Ueki, Miho Kaneto, Shogo Kitahata, Toshihiko Aibiki, Tomonari Okudaira, Hideomi Tomida, Yuji Miyamoto, Hiroka Yamago, Yoshifumi Suga, Ryuichiro Iwasaki, Kenichiro Mori, Hideki Miyata, Eiji Tsubouchi, Masato Kishida, Tomoyuki Ninomiya, Shigeru Kohgami, Masashi Hirooka, Yoshio Tokumoto, Masanori Abe, Bunzo Matsuura, Yoichi Hiasa
BACKGROUND/AIM: Sarcopenia is recognized as a condition related to quality of life and prognosis in patients with chronic liver disease, although no useful strategy for improving muscle volume and strength has been established. Here, we evaluated the efficacy of supplementation with branched-chain amino acid (BCAA) administration and walking exercise. PATIENTS AND METHODS: From December 2015 to July 2016, 33 Japanese outpatients with liver cirrhosis were enrolled (median: 67 years, HCV : HBV : alcohol : others=26 : 2 : 2 : 3, male : female=13 : 20, Child-Pugh A : B=30 : 3)...
December 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28987236/associations-of-cord-blood-metabolites-with-perinatal-characteristics-newborn-anthropometry-and-cord-blood-hormones-in-project-viva
#20
Wei Perng, Sheryl L Rifas-Shiman, Scott McCulloch, Leda Chatzi, Christos Mantzoros, Marie-France Hivert, Emily Oken
CONTEXT: Metabolomics has emerged as a powerful tool to characterize biomarkers and elucidate physiological processes underlying adverse health outcomes. Little is known of these relationships during gestation and infancy, which are critical period for development of metabolic disease risk. OBJECTIVES: To identify cord blood metabolite patterns associated with birth size; and to investigate relations of the birth size-associated metabolite patterns, and a branched chain amino acid (BCAA) metabolite pattern with a range of newborn and perinatal characteristics...
November 2017: Metabolism: Clinical and Experimental
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