Branched-chain amino acid

Aline Rissetti Roquetto, Carolina Soares Moura, Valfredo de Almeida Santos-Junior, Paulo Otávio Sammarco Oliveira, Karla Idelça Aires Machado, Gessika Cristina Borges Castro Carvalho, Eder Müller Risso, Jaime Amaya-Farfan
Notwithstanding the fact that dietary branched-chain amino acids (BCAAs) have been considered to be a cause of insulin resistance (IR), evidence indicates that BCAA-rich whey proteins (WPs) do not lead to IR in animals consuming high-fat (HF) diets and may instead improve glucose homeostasis. To address the role of BCAA-rich WP as dietary protein in IR and inflammatory response, we fed C57BL/6J mice either high-fat (HF) or low-fat (LF) diets formulated with moderate protein levels (13% w/w) of either WP or hydrolyzed WP (WPH) and compared them with casein (CAS) as a reference...
January 8, 2020: Journal of Nutritional Biochemistry
Chih-Yung Chiu, Mei-Ling Cheng, Meng-Han Chiang, Chia-Jung Wang, Ming-Han Tsai, Gigin Lin
Several metabolomics studies have identified altered metabolic pathways that are related to asthma. However, an integrative analysis of the metabolic responses across blood and urine for a comprehensive framework of asthma in early childhood remains lacking. Fifty-four age-matched children with asthma (n = 28) and healthy controls (n = 26) were enrolled. Metabolome analysis of the plasma and urine samples was performed using 1 H-nuclear magnetic resonance (NMR) spectroscopy coupled with partial least-squares discriminant analysis (PLS-DA)...
March 24, 2020: Journal of Clinical Medicine
Nicole Vogelzangs, Carla J H van der Kallen, Marleen M J van Greevenbroek, Birgitta W van der Kolk, Johan W E Jocken, Gijs H Goossens, Nicolaas C Schaper, Ronald M A Henry, Simone J P M Eussen, Armand Valsesia, Thomas Hankemeier, Arne Astrup, Wim H M Saris, Coen D A Stehouwer, Ellen E Blaak, Ilja C W Arts
BACKGROUND: Recent evidence indicates that insulin resistance (IR) in obesity may develop independently in different organs, representing different etiologies toward type 2 diabetes and other cardiometabolic diseases. The aim of this study was to investigate whether IR in the liver and IR in skeletal muscle are associated with distinct metabolic profiles. METHODS: This study includes baseline data from 634 adults with overweight or obesity (BMI ≥ 27 kg/m2 ) (≤65 years; 63% women) without diabetes of the European Diogenes Study...
March 17, 2020: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Guoqiang Han, Ning Xu, Xieping Sun, Jinzhao Chen, Chun Chen, Qing Wang
As one of the branched-chain amino acids, l-valine is an essential nutrient for most mammalian species. In this study, the l-valine producer Corynebacterium glutamicum ΔppcΔaceEΔalatΔpqo was first constructed. Additionally, an improved biosensor based on the Lrp-type transcriptional regulator and temperature-sensitive replication was built. Then, the C. glutamicum strain was mutagenized by atmospheric and room temperature plasma. A sequential three-step procedure was carried out to screen l-valine-producing strains, including the fluorescence-activated cell sorting (FACS), 96-well plate screening, and flask fermentation...
March 17, 2020: ACS Omega
Yanyan Xu, Haojie Jiang, Li Li, Fengwu Chen, Yunxia Liu, Meiyi Zhou, Ji Wang, Jingjing Jiang, Xiaoying Li, Xuemei Fan, Lin Zhang, Junfeng Zhang, Junqiang Qiu, Yi Wu, Chao Fang, Haipeng Sun, Junling Liu
Background: Branched-chain amino acids (BCAAs), essential nutrients including leucine, isoleucine and valine, serve as a resource for energy production and the regulator of important nutrient and metabolic signals. Recent studies have suggested that dysfunction of BCAA catabolism is associated with a risk of cardiovascular disease. Platelets play an important role in cardiovascular disease, but the functions of BCAA catabolism in platelets remain unknown. Methods: The activity of human platelets from healthy subjects before and after ingestion of BCAAs were measured...
March 23, 2020: Circulation
Jordi Mayneris-Perxachs, Josep Puig, Rémy Burcelin, Marc-Emmanuel Dumas, Richard H Barton, Lesley Hoyles, Massimo Federici, José-Manuel Fernández-Real
BACKGROUND & AIMS: Atherosclerosis is characterized by an inflammatory disease linked to excessive lipid accumulation in the artery wall. The Notch signalling pathway has been shown to play a key regulatory role in the regulation of inflammation. Recently, in vitro and pre-clinical studies have shown that apolipoprotein A-I binding protein (AIBP) regulates cholesterol metabolism (SREBP) and NOTCH signalling (haematopoiesis) and may be protective against atherosclerosis, but the evidence in humans is scarce...
March 8, 2020: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
Tenuun Bayaraa, Julia L Kurz, Khushboo M Patel, Waleed M Hussein, Jessica K Bilyj, Nicholas P West, Gerhard Schenk, Ross P McGeary, Luke William Guddat
Ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid biosynthesis pathway, is a potential drug target for bacterial infections including Mycobacterium tuberculosis . Here, we have screened the Medicines for Malaria Venture Pathogen Box against purified M. tuberculosis ( Mt ) KARI and identified two compounds that have K i values below 200 nM. In Mt cell susceptibility assays one of these compounds exhibited an IC 50 value of 0.8 μM. Co-crystallization of this compound, 3-((methylsulfonyl)methyl)-2 H -benzo[ b ][1,4]oxazin-2-one (MMV553002), in complex with Staphylococcus aureus KARI, which has 56% identity with Mt KARI, NADPH and Mg 2+ yielded a structure to 1...
March 21, 2020: Chemistry: a European Journal
Philipp Wuggenig, Berna Kaya, Hassan Melhem, C Korcan Ayata, Petr Hruz, A Emre Sayan, Hideki Tsumura, Morihiro Ito, Julien Roux, Jan Hendrik Niess
Comprehensive development is critical for gut macrophages being essential for the intestinal immune system. However, the underlying mechanisms of macrophage development in the colon remain elusive. To investigate the function of branched-chain amino acids in the development of gut macrophages, an inducible knock-out mouse model for the branched-chain amino acid transporter CD98hc in CX3CR1+ macrophages was generated. The relatively selective deletion of CD98hc in macrophage populations leads to attenuated severity of chemically-induced colitis that we assessed by clinical, endoscopic, and histological scoring...
2020: Communications Biology
Wei-Hua Sun, Bing-Bing Wu, Ya-Qiong Wang, Meng-Yuan Wu, Xin-Ran Dong, Yue-Ping Zhang, Wei Lu, Ping Zhang, Bin Yang, Min Zhang, Hong-Jiang Wu, Wen-Hao Zhou
BACKGROUND: Maple syrup urine disease (MSUD) is an autosomal recessive inherited disorder that affects the degradation of branched-chain amino acids and is associated with acute and chronic brain dysfunction. This study presents 11 new patients with MSUD and describes the clinical characteristics and gene mutations reported in Chinese individuals. METHODS: During 2011-2018, 11 pedaitric patients with MSUD from 11 Chinese families were analyzed based on clinical characteristics and mass spectrometry, with confirmation via gene sequencing...
March 19, 2020: World Journal of Pediatrics: WJP
Philipp Wuggenig, Berna Kaya, Hassan Melhem, C Korcan Ayata, Petr Hruz, A Emre Sayan, Hideki Tsumura, Morihiro Ito, Julien Roux, Jan Hendrik Niess
Comprehensive development is critical for gut macrophages being essential for the intestinal immune system. However, the underlying mechanisms of macrophage development in the colon remain elusive. To investigate the function of branched-chain amino acids in the development of gut macrophages, an inducible knock-out mouse model for the branched-chain amino acid transporter CD98hc in CX3CR1+ macrophages was generated. The relatively selective deletion of CD98hc in macrophage populations leads to attenuated severity of chemically-induced colitis that we assessed by clinical, endoscopic, and histological scoring...
March 18, 2020: Communications Biology
Huishou Zhao, Fuyang Zhang, Dan Sun, Xiong Wang, Xiaomeng Zhang, Jinglong Zhang, Feng Yan, Chong Huang, Huaning Xie, Chen Lin, Yi Liu, Miaomiao Fan, Wenjun Yan, Youhu Chen, Kun Lian, Yueyang Li, Ling Zhang, Shan Wang, Ling Tao
Branched chain amino acids (BCAAs) are associated with the progression of obesity-related metabolic disorders, including T2DM and non-alcoholic fatty liver disease. However, whether BCAAs disrupt the homeostasis of hepatic glucose and lipid metabolism remains unknown. In this study, we observed that BCAAs supplementation significantly reduced high-fat (HF) diet-induced hepatic lipid accumulation while increasing the plasma lipid levels and promoting muscular and renal lipid accumulation. Further studies demonstrated that BCAAs supplementation significantly increased hepatic gluconeogenesis and suppressed hepatic lipogenesis in HF diet-induced obese (DIO) mice...
March 17, 2020: Diabetes
Antonello E Rigamonti, Roberto Leoncini, Alessandra De Col, Sofia Tamini, Sabrina Cicolini, Laura Abbruzzese, Silvano G Cella, Alessandro Sartorio
The satiating effect of whey proteins depends upon their unique amino acid composition because there is no difference when comparing whey proteins or a mix of amino acids mimicking the amino acid composition of whey proteins. The specific amino acids underlying the satiating effect of whey proteins have not been investigated to date. AIMS AND METHODS: The aim of the present study was to evaluate the appetite-suppressant effect of an isocaloric drink containing whey proteins or maltodextrins on appetite (satiety/hunger measured by a visual analogue scale or VAS), anorexigenic gastrointestinal peptides (circulating levels of glucagon-like peptide 1 (GLP-1) and peptide tyrosine tyrosine (PYY)) and amino acids (circulating levels of single, total [TAA] and branched-chain amino acids [BCAA]) in a cohort of obese female subjects ( n = 8; age: 18...
March 15, 2020: Nutrients
Anna K Puszko, Piotr Sosnowski, Françoise Raynaud, Olivier Hermine, Gérard Hopfgartner, Yves Lepelletier, Aleksandra Misicka
The structure-activity relationship of branched H-Lys( h Arg)-Dab-Dhp-Arg-OH sequence analogues, modified with Cys-Asp or Cys at N-terminal amino acids (Lys, h Arg), in VEGF-A165 /Neuropilin-1 complex inhibition is presented. The addition of Cys residue led to a 100-fold decrease in the IC50 value, compared to the parent peptide. The change occurred regardless of coupling Cys to the free N-terminal amino group present in the main or the side chain. A few analogues extended by the attachment of Cys at the N-terminus of several potent NRP-1 peptide ligands documented in the literature are also presented...
March 13, 2020: Biomolecules
Itziar Lamiquiz-Moneo, Ana M Bea, Cristian Palacios-Pérez, Pilar De Miguel-Etayo, Esther M González-Gil, Chuan López-Ariño, Fernando Civeira, Luis A Moreno, Rocio Mateo-Gallego
INTRODUCTION: The global prevalence of type 2 diabetes (T2D) is increasing rapidly, especially in low- and middle-income countries and has a high number of associated comorbidities. Plasmatic concentrations of branched chain amino acids (BCAA) and retinol-binding protein 4 (RBP4) have been shown to be elevated in T2D subjects in cross-sectional studies. However, the effect of lifestyle community-based interventions on BCAA and RBP4 concentrations has not yet been analyzed. MATERIAL AND METHODS: The Feel4Diabetes study is a school and community-based intervention that identified 360 European families with a high risk of developing T2D according to the FINDRISC questionnaire...
March 12, 2020: Cells
J Tian, C Liu, X Zheng, X Jia, X Peng, R Yang, X Zhou, X Xu
Insulin resistance is one of the critical pathogeneses of type 2 diabetes mellitus (T2DM). Elevated levels of plasma branched-chain amino acids (BCAAs) are associated with insulin resistance. Recent studies have demonstrated the role of Porphyromonas gingivalis in the development of insulin resistance. However, the mechanisms by which P. gingivalis induces insulin resistance are still unclear. The purpose of this study was to investigate whether P. gingivalis induces insulin resistance through BCAA biosynthesis...
March 16, 2020: Journal of Dental Research
Limiao Jiang, Rengasamy Ramamoorthy, Srinivasan Ramachandran, Prakash P Kumar
Dwarfism and semi-dwarfism are among the most valuable agronomic traits in crop breeding, which were adopted by the "Green Revolution". Previously, we reported a novel semi-dwarf rice mutant ( oscyp96b4 ) derived from the insertion of a single copy of Dissociator (Ds) transposon into the gene OsCYP96B4 . However, the systems metabolic effect of the mutation is not well understood, which is important for understanding the gene function and developing new semi-dwarf mutants. Here, the metabolic phenotypes in the semi-dwarf mutant (M) and ectopic expression (ECE) rice line were compared to the wild-type (WT) rice, by using nuclear magnetic resonance (NMR) metabolomics and quantitative real-time polymerase chain reaction (qRT-PCR)...
March 11, 2020: International Journal of Molecular Sciences
Kota Arima, Mai Chan Lau, Melissa Zhao, Koichiro Haruki, Keisuke Kosumi, Kosuke Mima, Mancang Gu, Juha P Väyrynen, Tyler S Twombly, Yoshifumi Baba, Kenji Fujiyoshi, Junko Kishikawa, Chunguang Guo, Hideo Baba, William G Richards, Andrew T Chan, Reiko Nishihara, Jeffrey A Meyerhardt, Jonathan A Nowak, Marios Giannakis, Charles S Fuchs, Shuji Ogino
Accumulating evidence suggests that metabolic reprogramming has a critical role in carcinogenesis and tumor progression. The usefulness of formalin-fixed paraffin-embedded (FFPE) tissue material for metabolomics analysis as compared with fresh frozen tissue material remains unclear. Liquid chromatography tandem mass spectrometry-based metabolomics analysis was performed on 11 pairs of matched tumor and normal tissues in both FFPE and fresh frozen tissue materials from colorectal carcinoma patients. Permutation t-test was applied to identify metabolites with differential abundance between tumor and normal tissues...
March 12, 2020: Molecular Cancer Research: MCR
Agnieszka B Wegrzyn, Katharina Herzog, Albert Gerding, Marcel Kwiatkowski, Justina C Wolters, Amalia M Dolga, Alida E M van Lint, Ronald J A Wanders, Hans R Waterham, Barbara M Bakker
Refsum disease is an inborn error of metabolism that is characterised by a defect in peroxisomal α-oxidation of the branched-chain fatty acid phytanic acid. The disorder presents with late-onset progressive retinitis pigmentosa and polyneuropathy and can be diagnosed biochemically by elevated levels of phytanate in plasma and tissues of patients. To date, no cure exists for Refsum disease, but phytanate levels in patients can be reduced by plasmapheresis and a strict diet. In this study, we reconstructed a fibroblast-specific genome-scale model based on the recently published, FAD-curated model, based on Recon3D reconstruction...
March 11, 2020: FEBS Journal
Raphael Machado Castilhos, Marina Coutinho Augustin, José Augusto Dos Santos, José Luiz Pedroso, Orlando Barsottini, Roberta Saba, Henrique Ballalai Ferraz, Fernando Regla Vargas, Gabriel Vasata Furtado, Marcia Polese-Bonatto, Luiza Paulsen Rodrigues, Lucas Schenatto Sena, Carmen Regla Vargas, Maria Luiza Saraiva-Pereira, Laura Bannach Jardim, Rede Neurogenética
BACKGROUND: Huntington's disease (HD), caused by an expanded CAG repeat at HTT, has no treatment, and biomarkers are needed for future clinical trials. OBJECTIVE: The objective of this study was to verify if free carnitine and branched chain amino acids levels behave as potential biomarkers in HD. METHODS: Symptomatic and asymptomatic HD carriers and controls were recruited. Age, sex, body mass index (BMI), age of onset, disease duration, UHDRS scores, and expanded CAG tract were obtained; valine, leucine, isoleucine, and free carnitine were measured...
February 2020: Arquivos de Neuro-psiquiatria
Stefan Krywawych, Maureen Cleary, Mel McSweeney, Simon Heales
Earwax was investigated as a source to identify patients' different inborn errors of metabolism (IEMs). Acylcarnitines, amino acids, and guanidino metabolites were measured from 28 treated patients with 11 different metabolic disorders including 3 organic acidaemias, 2 fatty acid oxidation defects, 6 amino acid disorders, and 1 peroxisomal abnormality. On the basis of the ratio of different acylcarnitine species relative to free carnitine, isovaleric acidaemia, methylmalonic acidaemia, and long-chain hydroxyacylCoA dehydrogenase deficiency could be discriminated from the other disorders...
March 2020: JIMD Reports
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