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Altered tyrosine metabolism

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https://read.qxmd.com/read/30875680/vertical-sleeve-gastrectomy-improves-liver-and-hypothalamic-functions-in-obese-mice
#1
Peixin Li, Zhijian Rao, Brenton Laing, Wyatt Paul Bunner, Taylor Landry, Amber Prete, Yuan Yuan, Zhong-Tao Zhang, Hu Huang
Vertical sleeve gastrectomy (VSG) is an effective surgery to treat obesity and diabetes. However, the direct effect of VSG on metabolic functions is not fully understood. We aimed to investigate if alterations in hypothalamic neurons were linked with perturbations in liver metabolism after VSG in an energy intake-controlled obese mouse model. C57BL/6 and hrNPY-GFP reporter mice received HFD for 12 weeks and were then divided into three groups: Sham (ad lib), sham (pair-fed) with VSG, and VSG. Food intake was measured daily, and blood glucose levels were measured before and after the study...
March 1, 2019: Journal of Endocrinology
https://read.qxmd.com/read/30875096/impaired-clearance-of-sunitinib-leads-to-metabolic-disorders-and-hepatotoxicity
#2
Qi Zhao, Ting Zhang, Xue-Rong Xiao, Jian-Feng Huang, Yan Wang, Frank J Gonzalez, Fei Li
BACKGROUND AND PURPOSE: Sunitinib is a small molecule tyrosine kinase inhibitor associated with hepatotoxicity. The mechanisms of its toxicity are still unclear. EXPERIMENTAL APPROACH: In the present study, mice were treated with 60 mg kg-1, 150 mg kg-1, and 450 mg kg-1 sunitinib to evaluate sunitinib hepatotoxicity. Sunitinib metabolites and endogenous metabolites in liver, serum, feces, and urine were analyzed using ultra-performance liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry-based metabolomics...
March 15, 2019: British Journal of Pharmacology
https://read.qxmd.com/read/30870965/pharmacokinetic-and-metabolomic-studies-with-bio-300-a-nanosuspension-of-genistein-in-a-nonhuman-primate-model
#3
Amrita K Cheema, Khyati Y Mehta, Paola T Santiago, Oluseyi O Fatanmi, Michael D Kaytor, Vijay K Singh
Genistein is a naturally occurring phytoestrogen isoflavone and is the active drug ingredient in BIO 300, a radiation countermeasure under advanced development for acute radiation syndrome (H-ARS) and for the delayed effects of acute radiation exposure (DEARE). Here we have assessed the pharmacokinetics (PK) and safety of BIO 300 in the nonhuman primate (NHP). In addition, we analyzed serum samples from animals receiving a single dose of BIO 300 for global metabolomic changes using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight mass spectrometry (QTOF-MS)...
March 12, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30858393/alterations-in-the-tyrosine-and-phenylalanine-pathways-revealed-by-biochemical-profiling-in-cerebrospinal-fluid-of-huntington-s-disease-subjects
#4
Stephanie Herman, Valter Niemelä, Payam Emami Khoonsari, Jimmy Sundblom, Joachim Burman, Anne-Marie Landtblom, Ola Spjuth, Dag Nyholm, Kim Kultima
Huntington's disease (HD) is a severe neurological disease leading to psychiatric symptoms, motor impairment and cognitive decline. The disease is caused by a CAG expansion in the huntingtin (HTT) gene, but how this translates into the clinical phenotype of HD remains elusive. Using liquid chromatography mass spectrometry, we analyzed the metabolome of cerebrospinal fluid (CSF) from premanifest and manifest HD subjects as well as control subjects. Inter-group differences revealed that the tyrosine metabolism, including tyrosine, thyroxine, L-DOPA and dopamine, was significantly altered in manifest compared with premanifest HD...
March 11, 2019: Scientific Reports
https://read.qxmd.com/read/30844580/perfluoroalkyl-substances-metabolomic-profiling-and-alterations-in-glucose-homeostasis-among-overweight-and-obese-hispanic-children-a-proof-of-concept-analysis
#5
Tanya L Alderete, Ran Jin, Douglas I Walker, Damaskini Valvi, Zhanghua Chen, Dean P Jones, Cheng Peng, Frank D Gilliland, Kiros Berhane, David V Conti, Michael I Goran, Lida Chatzi
OBJECTIVE: To examine the prospective associations between exposure to perfluoroalkyl substances (PFASs) and longitudinal measurements of glucose metabolism in high-risk overweight and obese Hispanic children. METHODS: Forty overweight and obese Hispanic children (8-14 years) from urban Los Angeles underwent clinical measures and 2-hour oral glucose tolerance tests (OGTT) at baseline and a follow-up visit (range: 1-3 years after enrollment). Baseline plasma perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS), and the plasma metabolome were measured by liquid-chromatography with high-resolution mass spectrometry...
March 4, 2019: Environment International
https://read.qxmd.com/read/30826467/reduced-biliverdin-reductase-a-levels-are-associated-with-early-alterations-of-insulin-signaling-in-obesity
#6
Flavia Agata Cimini, Andrea Arena, Ilaria Barchetta, Antonella Tramutola, Valentina Ceccarelli, Chiara Lanzillotta, Mario Fontana, Laura Bertoccini, Frida Leonetti, Danila Capoccia, Gianfranco Silecchia, Claudio Di Cristofano, Caterina Chiappetta, Fabio Di Domenico, Marco Giorgio Baroni, Marzia Perluigi, Maria Gisella Cavallo, Eugenio Barone
Biliverdin reductase-A (BVR-A) is a serine/threonine/tyrosine kinase involved in the regulation of insulin signaling. In vitro studies have demonstrated that BVR-A is a substrate of the insulin receptor and regulates IRS1 by avoiding its aberrant activation, and in animal model of obesity the loss of hepatic BVR-A has been associated with glucose/insulin alterations and fatty liver disease. However, no studies exist in humans. Here, we evaluated BVR-A expression levels and activation in peripheral blood mononuclear cells (PBMC) from obese subjects and matched lean controls and we investigated the related molecular alterations of the insulin along with clinical correlates...
February 28, 2019: Biochimica et Biophysica Acta. Molecular Basis of Disease
https://read.qxmd.com/read/30826206/environmental-cadmium-exposure-induces-alterations-in-the-urinary-metabolic-profile-of-pregnant-women
#7
Han Li, Kai Huang, Shuna Jin, Yang Peng, Wenyu Liu, Mu Wang, Hongling Zhang, Bin Zhang, Wei Xia, Yuanyuan Li, Shi Lu, Shunqing Xu
Cadmium (Cd) is a well-recognized, hazardous toxic heavy metal, and the adverse effects of high-level Cd exposure on human health have been well documented. However, little is known about the health effects of low-level environmental Cd exposure on pregnant women. The objective of this study was to assess urinary metabolic alterations in pregnant women exposed to environmental Cd, and to identify informative biomarkers. Urine samples from 246 pregnant women in the first trimester of pregnancy were collected, and urinary Cd concentrations were quantified using inductively coupled plasma mass spectrometry (ICP-MS)...
February 27, 2019: International Journal of Hygiene and Environmental Health
https://read.qxmd.com/read/30816517/neuroprotection-of-hydroxysafflor-yellow-a-in-experimental-cerebral-ischemia-reperfusion-injury-via-metabolic-inhibition-of-phenylalanine-and-mitochondrial-biogenesis
#8
Suning Chen, Mao Sun, Xianghui Zhao, Zhifu Yang, Wenxing Liu, Jinyi Cao, Yi Qiao, Xiaoxing Luo, Aidong Wen
Stroke is the second most frequent cause of mortality, resulting in a huge societal burden worldwide. Timely reperfusion is the most effective therapy; however, it is difficult to prevent ischemia/reperfusion (I/R) injury. In traditional Chinese medicine, hydroxysafflor yellow A (HSYA) has been widely used for the treatment of cerebrovascular disease and as a protective therapy against I/R injury. Evidence has demonstrated that HSYA could reduce the levels of reactive oxygen species and suppress cellular apoptosis; however, whether HSYA alters the metabolic profile as its underlying mechanism for neuroprotection remains unknown...
February 15, 2019: Molecular Medicine Reports
https://read.qxmd.com/read/30804231/fructose-1-6-bis-phosphatase-getting-the-message-across
#9
David J Timson
Fructose 1,6- bis phosphatase (FBPase) is a key enzyme in gluconeogenesis.  It is a potential drug target in the treatment of type II diabetes.  The protein is also associated with a rare inherited metabolic disease and some cancer cells lack FBPase activity which promotes glycolysis facilitating the Warburg effect.  Thus, there is interest in both inhibiting the enzyme (for diabetes treatment) and restoring its activity (in relevant cancers).  The mammalian enzyme is tetrameric, competitively inhibited by Fructose 2,6- bis phosphate and negatively allosterically regulated by AMP...
February 25, 2019: Bioscience Reports
https://read.qxmd.com/read/30782595/a-comprehensive-lc-qtof-ms-metabolic-phenotyping-strategy-application-to-alkaptonuria
#10
Brendan P Norman, Andrew S Davison, Gordon A Ross, Anna M Milan, Andrew T Hughes, Hazel Sutherland, Jonathan C Jarvis, Norman B Roberts, James A Gallagher, Lakshminarayan R Ranganath
BACKGROUND: Identification of unknown chemical entities is a major challenge in metabolomics. To address this challenge, we developed a comprehensive targeted profiling strategy, combining 3 complementary liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) techniques and in-house accurate mass retention time (AMRT) databases established from commercial standards. This strategy was used to evaluate the effect of nitisinone on the urinary metabolome of patients and mice with alkaptonuria (AKU)...
February 19, 2019: Clinical Chemistry
https://read.qxmd.com/read/30756431/maternal-apical-periodontitis-is-associated-with-insulin-resistance-in-adult-offspring
#11
T V S Tsosura, F Y Chiba, M S L C Mattera, R F Pereira, L T A Cintra, L C Conti, R M Dos Santos, J H P Mateus, C A S Garbin, D H Sumida
AIM: To investigate the plasma concentrations of glucose, insulin, and tumour necrosis factor-α (TNF-α) of rats with maternal apical periodontitis (AP) and to explore the effect of maternal inflammation on the initial steps of insulin signaling and the inflammatory pathway in the gastrocnemius muscle (GM) and periepididymal white adipose tissue (pWAT) of adult offspring. METHODOLOGY: Fifteen female Wistar rats were distributed into a control group (CN), a group with 1 AP (1AP) and group with 4 AP (4AP)...
February 12, 2019: International Endodontic Journal
https://read.qxmd.com/read/30753112/amino-acid-and-fatty-acid-metabolomic-profile-during-fasting-and-hyperinsulinemia-in-girls-with-polycystic-ovarian-syndrome
#12
Melanie Cree-Green, Anne-Marie Carreau, Haseeb Rahat, Yesenia Garcia-Reyes, Bryan C Bergman, Laura Pyle, Kristen J Nadeau
Polycystic Ovarian Syndrome (PCOS) is associated with insulin resistance (IR) and altered muscle mitochondrial oxidative phosphorylation. IR in adults with obesity and diabetes is associated with changes in amino acid, free fatty acid (FFA) and mitochondrial acylcarnitine (AC) metabolism. We sought to determine if these metabolites are associated with IR and/or androgens in youth-onset PCOS. We enrolled obese girls with PCOS [n = 15, 14.5 ± 1.6 years, BMI %ile 98.5 ± 1.0] and without PCOS [n = 6, 13.2 ± 1...
February 12, 2019: American Journal of Physiology. Endocrinology and Metabolism
https://read.qxmd.com/read/30739038/administration-of-tetrahydrobiopterin-restored-the-decline-of-dopamine-in-the-striatum-induced-by-an-acute-action-of-mptp
#13
Hiroki Kurosaki, Kentaro Yamaguchi, Kohei Man-Yoshi, Shin-Ichi Muramatsu, Satoshi Hara, Hiroshi Ichinose
Parkinson's disease (PD) is the second common neurodegenerative disorder. Deficit of the nigro-striatal dopaminergic neurons causes the motor symptoms of PD. While the oxidative stress is thought to be deeply involved in the etiology of PD, molecular targets for the oxidative insults has not been fully elucidated. 6R-5,6,7,8-Tetrahydrobiopterin (BH4) is a cofactor for tyrosine hydroxylase (TH), the rate-limiting enzyme for production of dopamine, and easily oxidized to its dihydro-form. In this study, we examined the alteration in the metabolism of BH4 caused by a parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)...
February 7, 2019: Neurochemistry International
https://read.qxmd.com/read/30737597/adhd-pathogenesis-in-the-immune-endocrine-and-nervous-systems-of-juvenile-and-maturating-shr-and-wky-rats
#14
Anna Kozłowska, Paweł Wojtacha, Maciej Równiak, Małgorzata Kolenkiewicz, Andrew Chih Wei Huang
RATIONALE: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurobehavioural disorders with morphological and functional brain abnormalities. However, there is a growing body of evidence that abnormalities in the immune and endocrine systems may also account for the ADHD pathogenesis. OBJECTIVES: To test ADHD pathogenesis in neurological, immune and endocrine systems, this study examined the concentrations of cytokines, chemokines, oxidative stress markers, metabolic parameters, steroid hormones and steroidogenic enzymes in the serum and/or tissues of spontaneously hypertensive rats (SHRs, animal model of ADHD) and Wistar Kyoto rats (WKYs, control animals)...
February 8, 2019: Psychopharmacology
https://read.qxmd.com/read/30735834/cd36-dependent-redoxosomes-promotes-ceramide-mediated-pancreatic-%C3%AE-cell-failure-via-p66shc-activation
#15
Udayakumar Karunakaran, Suma Elumalai, Jun Sung Moon, Kyu Chang Won
Altered metabolism is implicated in the pathogenesis of beta-cell failure in type 2 diabetes (T2D). Plasma and tissue levels of ceramide species play positive roles in inflammatory and oxidative stress responses in T2D. However, oxidative targets and mechanisms underlying ceramide signaling are unclear. We investigated the role of CD36-dependent redoxosome (redox-active endosome), a membrane-based signaling agent, in ceramide-induced beta-cell dysfunction and failure. Exposure of beta cells to C2-ceramide (N-acetyl-sphingosine) induced a CD36-dependent non-receptor tyrosine kinase Src-mediated redoxosome (Vav2-Rac1-NOX) formation...
February 5, 2019: Free Radical Biology & Medicine
https://read.qxmd.com/read/30734239/competitive-endogenous-rna-cerna-regulation-network-of-lncrna-mirna-mrna-in-colorectal-carcinogenesis
#16
Jingwei Liu, Hao Li, Bowen Zheng, Liping Sun, Yuan Yuan, Chengzhong Xing
BACKGROUND: Competitive endogenous RNA (ceRNA) regulation suggested complex network of all transcript RNAs including long noncoding RNAs (lncRNAs), which can act as natural miRNA sponges to inhibit miRNA functions and modulate mRNA expression. Until now, the specific ceRNA regulatory mechanism of lncRNA-miRNA-mRNA in colorectal cancer (CRC) still remains unclear. MATERIALS AND METHODS: RNA sequencing data of 478 colon adenocarcinoma cases and 41 controls as well as 166 rectum adenocarcinoma cases and 10 controls were obtained from The Cancer Genome Atlas (TCGA) to investigate the significant changes of lncRNAs, miRNAs and mRNAs in colorectal carcinogenesis...
February 7, 2019: Digestive Diseases and Sciences
https://read.qxmd.com/read/30733286/ahr-controls-redox-homeostasis-and-shapes-the-tumor-microenvironment-in-brca1-associated-breast-cancer
#17
Shawn P Kubli, Christian Bassi, Cecilia Roux, Andrew Wakeham, Christoph Göbl, Wenjing Zhou, Soode Moghadas Jafari, Bryan Snow, Lisa Jones, Luis Palomero, Kelsie L Thu, Luca Cassetta, Daniel Soong, Thorsten Berger, Parameswaran Ramachandran, Shakiba P Baniasadi, Gordon Duncan, Moshit Lindzen, Yosef Yarden, Carmen Herranz, Conxi Lazaro, Mandy F Chu, Jillian Haight, Paul Tinto, Jennifer Silvester, David W Cescon, Anna Petit, Sven Pettersson, Jeffrey W Pollard, Tak W Mak, Miguel A Pujana, Paola Cappello, Chiara Gorrini
Cancer cells have higher reactive oxygen species (ROS) than normal cells, due to genetic and metabolic alterations. An emerging scenario is that cancer cells increase ROS to activate protumorigenic signaling while activating antioxidant pathways to maintain redox homeostasis. Here we show that, in basal-like and BRCA1-related breast cancer (BC), ROS levels correlate with the expression and activity of the transcription factor aryl hydrocarbon receptor (AhR). Mechanistically, ROS triggers AhR nuclear accumulation and activation to promote the transcription of both antioxidant enzymes and the epidermal growth factor receptor (EGFR) ligand, amphiregulin (AREG)...
February 7, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/30707914/local-and-systemic-metabolic-alterations-in-brain-plasma-and-liver-of-rats-in-response-to-aging-and-ischemic-stroke-as-detected-by-nuclear-magnetic-resonance-nmr-spectroscopy
#18
Umadevi V Wesley, Vijesh J Bhute, James F Hatcher, Sean P Palecek, Robert J Dempsey
Metabolic dysfunction impacts stroke incidence and outcome. However, the intricate association between altered metabolic program due to aging, and focal ischemia in brain, circulation, and peripheral organs is not completely elucidated. Here we identified locally and systemically altered metabolites in brain, liver, and plasma as a result of normal aging, ischemic-stroke, and extended time of reperfusion injury. Comprehensive quantitative metabolic profiling was carried out using nuclear magnetic resonance spectroscopy...
January 29, 2019: Neurochemistry International
https://read.qxmd.com/read/30696813/altered-gut-metabolome-contributes-to-depression-like-behaviors-in-rats-exposed-to-chronic-unpredictable-mild-stress
#19
Li Jianguo, Jia Xueyang, Wang Cui, Wu Changxin, Qin Xuemei
The gut microbiota has been increasingly correlated with depressive disorder. It was recently shown that the transplantation of the gut microbiota from depressed patients to animals can produce depressive-like behaviors, suggesting that the gut microbiota plays a causal role in the development of depression. In addition, metabolic disorder, which is strongly associated with depression, is exacerbated by changes in the composition of the gut microbiota and is alleviated by treatment with antidepressants. However, the key players and pathways that link the gut microbiota to the pathogenesis of depression remain largely unknown...
January 29, 2019: Translational Psychiatry
https://read.qxmd.com/read/30692269/imp2-increases-mouse-skeletal-muscle-mass-and-voluntary-activity-by-enhancing-autocrine-igf2-production-and-optimizing-muscle-metabolism
#20
Laura Regué, Fei Ji, Daniel Flicker, Dana Kramer, William Pierce, Teekhon Davidoff, Jeffrey J Widrick, Nicholas Houstis, Liliana Minichiello, Ning Dai, Joseph Avruch
The IGF2 mRNA binding protein2/IMP2 was selectively deleted from adult mouse muscle; two phenotypes were observed: decreased accrual of skeletal muscle mass after weaning and reduced wheel running activity but normal forced treadmill performance. Reduced wheel running occurs when fed a high fat diet but is normalized consuming standard chow. The two phenotypes are due to altered abundance of different IMP2 client mRNAs. The reduced fiber size of IMP2 deficient muscle is attributable, in part, to diminished autocrine Igf2 production; basal tyrosine phosphorylation of the Insulin and IGF1 receptors is diminished and Akt1 activation is selectively reduced...
January 28, 2019: Molecular and Cellular Biology
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