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https://www.readbyqxmd.com/read/28937600/the-gut-microbial-metabolite-trimethylamine-n-oxide-is-present-in-human-cerebrospinal-fluid
#1
Daniele Del Rio, Francesca Zimetti, Paolo Caffarra, Michele Tassotti, Franco Bernini, Furio Brighenti, Andrea Zini, Ilaria Zanotti
Trimethylamine-N-oxide (TMAO) is a small organic molecule, derived from the intestinal and hepatic metabolism of dietary choline and carnitine. Although the involvement of TMAO in the framework of many chronic diseases has been recently described, no evidence on its putative role in the central nervous system has been provided. The aim of this study was to evaluate whether TMAO is present at detectable levels in human cerebrospinal fluid (CSF). CSF was collected for diagnostic purposes from 58 subjects by lumbar puncture and TMAO was quantified by using liquid chromatography coupled with multiple-reaction monitoring mass spectrometry...
September 22, 2017: Nutrients
https://www.readbyqxmd.com/read/28934691/the-role-of-ppar-alpha-in-perfluorooctanoic-acid-induced-developmental-cardiotoxicity-and-l-carnitine-mediated-protection-results-of-in-ovo-gene-silencing
#2
Meng Zhao, Qixiao Jiang, Min Geng, Li Zhu, Yunqiu Xia, Aashish Khanal, Chunbo Wang
Perfluorooctanoic acid (PFOA) is a persistent organic pollutant. This study established an in ovo peroxisome proliferator-activated receptor alpha (PPAR alpha) silencing model in chicken embryo heart, and investigated the role of PPAR alpha in PFOA induced developmental cardiotoxicity. The in ovo silencing was achieved by introducing lentivirus expressing PPAR alpha siRNA into ED2 chicken embryo via microinjection (0.05ul/g egg weight). Transfection efficacy was confirmed by fluorescent microscopy and western blotting...
September 14, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28921605/simple-determination-of-betaine-l-carnitine-and-choline-in-human-urine-using-self-packed-column-and-column-switching-ion-chromatography-with-non-suppressed-conductivity-detection
#3
Dan Wei, Yan Zhu, Ming Guo
A sequential on-line extraction, clean-up and separation system for the determination of betaine, L-carnitine and choline in human urine using column-switching ion chromatography with non-suppressed conductivity detection was developed in this work. Self-packed pretreatment column (50 mm×4.6 mm, i.d.) was used for the extraction and clean-up of betaine, L-carnitine and choline. The separation was achieved using self-packed cationic exchange column (150 mm×4.6 mm, i.d.), followed by non-suppressed conductivity detection...
September 15, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28919076/mitochondrial-priming-by-cd28
#4
Ramon I Klein Geltink, David O'Sullivan, Mauro Corrado, Anna Bremser, Michael D Buck, Joerg M Buescher, Elke Firat, Xuekai Zhu, Gabriele Niedermann, George Caputa, Beth Kelly, Ursula Warthorst, Anne Rensing-Ehl, Ryan L Kyle, Lana Vandersarren, Jonathan D Curtis, Annette E Patterson, Simon Lawless, Katarzyna Grzes, Jing Qiu, David E Sanin, Oliver Kretz, Tobias B Huber, Sophie Janssens, Bart N Lambrecht, Angelika S Rambold, Edward J Pearce, Erika L Pearce
T cell receptor (TCR) signaling without CD28 can elicit primary effector T cells, but memory T cells generated during this process are anergic, failing to respond to secondary antigen exposure. We show that, upon T cell activation, CD28 transiently promotes expression of carnitine palmitoyltransferase 1a (Cpt1a), an enzyme that facilitates mitochondrial fatty acid oxidation (FAO), before the first cell division, coinciding with mitochondrial elongation and enhanced spare respiratory capacity (SRC). microRNA-33 (miR33), a target of thioredoxin-interacting protein (TXNIP), attenuates Cpt1a expression in the absence of CD28, resulting in cells that thereafter are metabolically compromised during reactivation or periods of increased bioenergetic demand...
September 1, 2017: Cell
https://www.readbyqxmd.com/read/28916721/loss-of-cardiac-carnitine-palmitoyltransferase-2-results-in-rapamycin-resistant-acetylation-independent-hypertrophy
#5
Andrea S Pereyra, Like Y Hasek, Kate L Harris, Alycia G Berman, Frederick W Damen, Craig J Goergen, Jessica M Ellis
Cardiac hypertrophy is closely linked to impaired fatty acid oxidation, but the molecular basis of this link is unclear. Here, we investigated the loss of an obligate enzyme in mitochondrial long-chain fatty acid oxidation, carnitine palmitoyltransferase 2 (CPT2), on muscle and heart structure, function, and molecular signatures in a muscle- and heart-specific CPT2-deficient mouse (Cpt2M-/-) model. CPT2 loss in heart and muscle reduced complete oxidation of long-chain fatty acids by 87% and 69%, respectively, without altering body weight, energy expenditure, respiratory quotient, or adiposity...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28914566/a-novel-etfdh-mutation-in-an-adult-patient-with-late-onset-riboflavin-responsive-multiple-acyl-coa-dehydrogenase-deficiency
#6
Min Chen, Jing Peng, Wei Wei, Wang, Hongliang Xu, Hongbo Liu
We report a novel mutation in the electron transfer flavoprotein dehydrogenase (ETFDH) gene in an adult patient with late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD) characterized by muscle weakness and hypoglycemia as main clinical presentation. At the age of 34 years, the patient experienced progressive muscle weakness and short of breath. Blood creatine kinase level was significantly higher than normal. The blood glucose was significantly lower than normal. The muscle biopsy revealed lipid storage myopathy...
September 15, 2017: International Journal of Neuroscience
https://www.readbyqxmd.com/read/28912919/intravenous-carnitine-administration-in-addition-to-parenteral-nutrition-with-lipid-emulsion-may-decrease-the-inflammatory-reaction-in-postoperative-surgical-patients
#7
Yu Koyama, Kazuki Moro, Masato Nakano, Kohei Miura, Masayuki Nagahashi, Shin-Ichi Kosugi, Junko Tsuchida, Mayuko Ikarashi, Masato Nakajima, Hiroshi Ichikawa, Takaaki Hanyu, Yoshifumi Shimada, Jun Sakata, Hitoshi Kameyama, Takashi Kobayashi, Toshifumi Wakai
BACKGROUND: A prospective randomized study was performed to investigate the validity of intravenous carnitine administration during postoperative parenteral nutrition (PN) with lipid emulsion. METHODS: Patients undergoing surgery for gastric or colorectal cancer were enrolled in the study and were randomly divided into two groups (n = 8 in each group): 1) group L, who received a peripheral PN (PPN) solution of 7.5% glucose, 30% amino acid, and 20% lipid emulsion; and 2) group LC, who received the same PPN solution, as well as carnitine intravenously...
October 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28911246/dual-targeting-of-l-carnitine-conjugated-nanoparticles-to-octn2-and-atb-0-to-deliver-chemotherapeutic-agents-for-colon-cancer-therapy
#8
Longfa Kou, Qing Yao, Sathish Sivaprakasam, Qiuhua Luo, Yinghua Sun, Qiang Fu, Zhonggui He, Jin Sun, Vadivel Ganapathy
l-Carnitine, obligatory for oxidation of fatty acids, is transported into cells by the Na(+)-coupled transporter OCTN2 and the Na(+)/Cl(-)-coupled transporter ATB(0,+). Here we investigated the potential of L-carnitine-conjugated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (LC-PLGA NPs) to deliver chemotherapeutic drugs into cancer cells by targeting the nanoparticles to both OCTN2 and ATB(0,+). The cellular uptake of LC-PLGA NPs in the breast cancer cell line MCF7 and the colon cancer cell line Caco-2 was increased compared to unmodified nanoparticles, but decreased in the absence of co-transporting ions (Na(+) and/or Cl(-)) or in the presence of competitive substrates for the two transporters...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28895586/maresin-1-mitigates-liver-steatosis-in-ob-ob-and-diet-induced-obese-mice
#9
L M Laiglesia, S Lorente-Cebrián, L Martínez-Fernández, N Sáinz, P L Prieto-Hontoria, M A Burrell, C M Rodríguez-Ortigosa, J A Martínez, M J Moreno-Aliaga
BACKGROUND/OBJECTIVES: The aim of this study was to characterize the effects of Maresin 1 (MaR1) in obesity-related liver steatosis and the mechanisms involved. METHODS: MaR1 effects on fatty liver disease were tested in ob/ob (2-10 μg/kg i.p., 20 days) and in diet-induced obese (DIO) mice (2 μg/kg, i.p., or 50 μg/kg, oral gavage for 10 days), as well as in cultured hepatocytes. RESULTS: In ob/ob mice, MaR1 reduced liver triglycerides (TG) content, fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 protein expression, while increased acetyl-CoA carboxylase (ACC) phosphorylation and LC3II protein expression, in parallel with a drop in p62 levels...
September 12, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28892370/mass-spectrometry-based-chemical-cartography-of-a-cardiac-parasitic-infection
#10
Laura-Isobel McCall, James T Morton, Jean A Bernatchez, Jair Lage de Siqueira-Neto, Rob Knight, Pieter C Dorrestein, James H McKerrow
Trypanosoma cruzi parasites are the causative agents of Chagas disease, a leading infectious form of heart failure whose pathogenesis is still not fully characterized. In this work, we applied untargeted liquid chromatography-tandem mass spectrometry to heart sections from T. cruzi-infected and uninfected mice. We combined molecular networking and three-dimensional modeling to generate chemical cartographical heart models. This approach revealed for the first time preferential parasite localization to the base of the heart and regiospecific distributions of nucleoside derivatives and eicosanoids, which we correlated to tissue-damaging immune responses...
September 22, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28891931/beneficial-effects-of-common-bean-on-adiposity-and-lipid-metabolism
#11
Henry J Thompson, John N McGinley, Elizabeth S Neil, Mark A Brick
In developed countries which are at the epicenter of the obesity pandemic, pulse crop consumption is well below recommended levels. In a recent systematic review and meta-analysis of 21 randomized controlled clinical trials, pulse consumption was associated with improved weight control and reduced adiposity, although the underlying mechanisms were a matter of speculation. Common bean (Phaseolus vulgaris L.) is the most widely consumed pulse crop and was the focus of this investigation. Using outbred genetic models of dietary induced obesity resistance and of dietary induced obesity sensitivity in the rat, the impact of bean consumption was investigated on the efficiency with which consumed food was converted to body mass (food efficiency ratio), body fat accumulation, adipocyte morphometrics, and patterns of protein expression associated with lipid metabolism...
September 9, 2017: Nutrients
https://www.readbyqxmd.com/read/28877455/global-analysis-of-plasma-lipids-identifies-liver-derived-acylcarnitines-as-a-fuel-source-for-brown-fat-thermogenesis
#12
Judith Simcox, Gisela Geoghegan, John Alan Maschek, Claire L Bensard, Marzia Pasquali, Ren Miao, Sanghoon Lee, Lei Jiang, Ian Huck, Erin E Kershaw, Anthony J Donato, Udayan Apte, Nicola Longo, Jared Rutter, Renate Schreiber, Rudolf Zechner, James Cox, Claudio J Villanueva
Cold-induced thermogenesis is an energy-demanding process that protects endotherms against a reduction in ambient temperature. Using non-targeted liquid chromatography-mass spectrometry-based lipidomics, we identified elevated levels of plasma acylcarnitines in response to the cold. We found that the liver undergoes a metabolic switch to provide fuel for brown fat thermogenesis by producing acylcarnitines. Cold stimulates white adipocytes to release free fatty acids that activate the nuclear receptor HNF4α, which is required for acylcarnitine production in the liver and adaptive thermogenesis...
September 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28872093/-research-progress-of-trimethylamine-n-oxide-in-the-pathogenesis-of-atherosclerosis
#13
Huahua He, Xinfu Lian, Zhiqun Tang
Trimethylamine-N-oxide (TMAO), metabolites of the intestinal microflora, is a newly discovered risk factor for cardiovascular disease. The intestinal flora converted choline and L-carnitine into trimethylamine in the food. Trimethylamine is oxidized to TMAO in liver enzymes. Lowering TMA can stimulate macrophages to reverse cholesterol transport and inhibit atherogenesis. TMAO poietin-monooxygenase 3 (FMO3) is a tool for cholesterol metabolism and reverse cholesterol transpor, lowering FMO3 can slow the gallbladder's secretion of bile, delay intestinal absorption of cholesterol, and limit the synthesis of oxidized cholesterol and cholesterol esters...
August 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28870581/pharmacological-treatments-for-fatigue-in-patients-with-multiple-sclerosis-a-systematic-review-and-meta-analysis
#14
Ting-Ting Yang, Li Wang, Xiao-Yang Deng, Gang Yu
BACKGROUND: Multiple sclerosis (MS) is a chronic immune-mediated inflammatory disease. Fatigue is the most common symptom of MS patients, affecting >80% subjects. Medical treatment is an important method for managing fatigue. Currently, although many drugs have been tested in treatment of MS fatigue, the efficacy of these drugs remain largely unclear. METHODS: We researched available literatures in PubMed, Embase, Medline, Google Scholar, Cochrane Library (August 31, 2016)...
September 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28866892/plasma-l-carnitine-levels-in-terminally-ill-cancer-patients-receiving-only-palliative-care
#15
Akiyuki Sakamoto, Yoshiko Tsukahara, Daisuke Gomi, Toshirou Fukushima, Takashi Kobayashi, Hirohide Matsushita, Nodoka Sekiguchi, Keiko Mamiya, Tomonobu Koizumi
BACKGROUND: Several studies indicated that plasma L-carnitine (LC) levels are significantly decreased during chemotherapy or chemoradiation and that LC supplementation can improve the fatigue score in some cancer patients. However, the LC levels in end-stage cancer patients treated only with palliative care remained unclear. The present study was performed to examine the plasma LC levels of terminally ill and hospitalized patients. METHODS: Twenty-one terminally ill cancer patients in our hospital, with expected survival of several months, were enrolled in the present study...
August 2017: Annals of Palliative Medicine
https://www.readbyqxmd.com/read/28862226/serum-metabolomics-in-oral-leukoplakia-and-oral-squamous-cell-carcinoma
#16
Gokul Sridharan, Pratibha Ramani, Sangeeta Patankar
CONTEXT: Metabolomics is a core discipline of system biology focusing on the study of low molecular weight compounds in biological system. Analysis of human metabolome, which is composed of diverse group of metabolites, can aid in diagnosis and prognosis of oral squamous cell carcinoma (OSCC). AIM: The aim of the present study is to analyze and identify serum metabolites in oral leukoplakia and OSCC as a potential diagnostic biomarker and a predictor for malignant transformation of oral leukoplakia...
July 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28862145/expanded-newborn-metabolic-screening-programme-in-hong-kong-a-three-year-journey
#17
S C Chong, L K Law, J Hui, C Y Lai, T Y Leung, Y P Yuen
INTRODUCTION: No universal expanded newborn screening service for inborn errors of metabolism is available in Hong Kong despite its long history in developed western countries and rapid development in neighbouring Asian countries. To increase the local awareness and preparedness, the Centre of Inborn Errors of Metabolism of the Chinese University of Hong Kong started a private inborn errors of metabolism screening programme in July 2013. This study aimed to describe the results and implementation of this screening programme...
September 1, 2017: Hong Kong Medical Journal, Xianggang Yi Xue za Zhi
https://www.readbyqxmd.com/read/28857146/recessive-mutations-in-ndufa2-cause-mitochondrial-leukoencephalopathy
#18
S Perrier, L Gauquelin, M Tétreault, L Tran, N Webb, M Srour, J J Mitchell, C Brunel-Guitton, J Majewski, V Long, S Keller, M J Gambello, C Simons, A Vanderver, G Bernard
Deficiencies of mitochondrial respiratory chain complex I frequently result in leukoencephalopathy in young patients, and different mutations in the genes encoding its subunits are still being uncovered. We report two patients with cystic leukoencephalopathy and complex I deficiency with recessive mutations in NDUFA2, an accessory subunit of complex I. The first patient was initially diagnosed with a primary systemic carnitine deficiency associated with a homozygous variant in SLC22A5, but also exhibited developmental regression and cystic leukoencephalopathy, and an additional diagnosis of complex I deficiency was suspected...
August 30, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28855839/ameliorative-effects-of-l-carnitine-on-rats-raised-on-a-diet-supplemented-with-lead-acetate
#19
El-Said El-Sherbini, Gehad El-Sayed, Rehab El Shotory, Nervana Gheith, Mohamed Abou-Alsoud, Steve Mustapha Harakeh, Gamal I Karrouf
Lead intoxication has been a major health hazard in humans. It affects people at all ages. Its toxicity is associated with various organs of the body and affects different metabolic pathways. Based on histological data, l-carnitine reduced the severity of tissue damage produced as a result of exposure of rats to lead acetate. The main objective of this study was to evaluate the underlying mechanism of protection offered by l-carnitine against lead acetate intoxication using male Sprague-Dawley rats. Forty male Sprague-Dawley rats were randomly divided into four groups with ten rats in each...
September 2017: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/28854364/a-fatty-acid-oxidation-dependent-metabolic-shift-regulates-adult-neural-stem-cell-activity
#20
Marlen Knobloch, Gregor-Alexander Pilz, Bart Ghesquière, Werner J Kovacs, Thomas Wegleiter, Darcie L Moore, Martina Hruzova, Nicola Zamboni, Peter Carmeliet, Sebastian Jessberger
Hippocampal neurogenesis is important for certain forms of cognition, and failing neurogenesis has been implicated in neuropsychiatric diseases. The neurogenic capacity of hippocampal neural stem/progenitor cells (NSPCs) depends on a balance between quiescent and proliferative states. Here, we show that the rate of fatty acid oxidation (FAO) regulates the activity of NSPCs. Quiescent NSPCs show high levels of carnitine palmitoyltransferase 1a (Cpt1a)-dependent FAO, which is downregulated in proliferating NSPCs...
August 29, 2017: Cell Reports
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