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https://www.readbyqxmd.com/read/28425060/positron-emission-tomography-assessment-of-cerebral-glucose-metabolic-rates-in-autism-spectrum-disorder-and-schizophrenia
#1
Serge A Mitelman, Marie-Cecile Bralet, M Mehmet Haznedar, Eric Hollander, Lina Shihabuddin, Erin A Hazlett, Monte S Buchsbaum
Several models have been proposed to account for observed overlaps in clinical features and genetic predisposition between schizophrenia and autism spectrum disorder. This study assessed similarities and differences in topological patterns and vectors of glucose metabolism in both disorders in reference to these models. Co-registered (18)fluorodeoxyglucose PET and MRI scans were obtained in 41 schizophrenia, 25 ASD, and 55 healthy control subjects. AFNI was used to map cortical and subcortical regions of interest...
April 19, 2017: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/28422055/c-myc-making-liver-sick-role-of-c-myc-in-hepatic-cell-function-homeostasis-and-disease
#2
REVIEW
Kang Zheng, Francisco Javier Cubero, Yulia A Nevzorova
Over 35 years ago, c-MYC, a highly pleiotropic transcription factor that regulates hepatic cell function, was identified. In recent years, a considerable increment in the number of publications has significantly shifted the way that the c-MYC function is perceived. Overexpression of c-MYC alters a wide range of roles including cell proliferation, growth, metabolism, DNA replication, cell cycle progression, cell adhesion and differentiation. The purpose of this review is to broaden the understanding of the general functions of c-MYC, to focus on c-MYC-driven pathogenesis in the liver, explain its mode of action under basal conditions and during disease, and discuss efforts to target c-MYC as a plausible therapy for liver disease...
April 19, 2017: Genes
https://www.readbyqxmd.com/read/28421296/metabolite-signatures-of-doxorubicin-induced-toxicity-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#3
Umesh Chaudhari, James K Ellis, Vilas Wagh, Harshal Nemade, Jürgen Hescheler, Hector C Keun, Agapios Sachinidis
Drug-induced off-target cardiotoxicity, particularly following anti-cancer therapy, is a major concern in new drug discovery and development. To ensure patient safety and efficient pharmaceutical drug development, there is an urgent need to develop more predictive cell model systems and distinct toxicity signatures. In this study, we applied our previously proposed repeated exposure toxicity methodology and performed (1)H NMR spectroscopy-based extracellular metabolic profiling in culture medium of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) exposed to doxorubicin (DOX), an anti-cancer agent...
April 18, 2017: Amino Acids
https://www.readbyqxmd.com/read/28420713/acute-versus-chronic-exposure-to-high-fat-diet-leads-to-distinct-regulation-of-pka
#4
Edra London, Maria Nesterova, Constantine A Stratakis
The cAMP-dependent protein kinase (PKA) is an essential regulator of lipid and glucose metabolism that plays a critical role in energy homeostasis. The impact of diet on PKA signaling has not been defined, although perturbations in individual PKA subunits are associated with changes in adiposity, physical activity, and energy intake in mice and humans. We hypothesized that a high fat diet (HFD) would elicit peripheral and central alterations in the PKA system that would differ depending on length of exposure to HFD; these differences could protect against or promote diet-induced obesity (DIO)...
April 18, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28417532/non-alcoholic-fatty-liver-disease-nafld-prevalence-and-its-metabolic-associations-in-patients-with-type-1-diabetes-and-type-2-diabetes
#5
Kenneth Cusi, Arun J Sanyal, Shuyu Zhang, Mark L Hartman, Juliana M Bue-Valleskey, Byron J Hoogwerf, Axel Haupt
We investigated non-alcoholic fatty liver disease (NAFLD) prevalence and its metabolic associations in patients with type 1 diabetes (T1D), and in insulin-naïve and insulin-treated patients with type 2 diabetes (T2D). Baseline data from patients who had liver fat content (LFC) evaluated by magnetic resonance imaging in 4 phase 3 studies of basal insulin peglispro (BIL) were analyzed. Associations of NAFLD with clinical characteristics, glycemic control and diabetes therapy were evaluated. The prevalence of NAFLD (defined as LFC ≥6%) was low in T1D (8...
April 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28412757/fatty-acid-metabolism-in-breast-cancer-subtypes
#6
REVIEW
Marie E Monaco
Dysregulation of fatty acid metabolism is recognized as a component of malignant transformation in many different cancers, including breast; yet the potential for targeting this pathway for prevention and/or treatment of cancer remains unrealized. Evidence indicates that proteins involved in both synthesis and oxidation of fatty acids play a pivotal role in the proliferation, migration and invasion of breast cancer cells. The following essay summarizes data implicating specific fatty acid metabolic enzymes in the genesis and progression of breast cancer, and further categorizes the relevance of specific metabolic pathways to individual intrinsic molecular subtypes of breast cancer...
February 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410378/metabolic-changes-and-inflammation-in-cultured-astrocytes-from-the-5xfad-mouse-model-of-alzheimer-s-disease-alleviation-by-pantethine
#7
Manuel van Gijsel-Bonnello, Kévin Baranger, Philippe Benech, Santiago Rivera, Michel Khrestchatisky, Max de Reggi, Bouchra Gharib
Astrocytes play critical roles in central nervous system homeostasis and support of neuronal function. A better knowledge of their response may both help understand the pathophysiology of Alzheimer's disease (AD) and implement new therapeutic strategies. We used the 5xFAD transgenic mouse model of AD (Tg thereafter) to generate astrocyte cultures and investigate the impact of the genotype on metabolic changes and astrocytes activation. Metabolomic analysis showed that Tg astrocytes exhibited changes in the glycolytic pathway and tricarboxylic acid (TCA) cycle, compared to wild type (WT) cells...
2017: PloS One
https://www.readbyqxmd.com/read/28408641/gastroparesis-and-lipid-metabolism-associated-dysbiosis-in-wistar-kyoto-rats
#8
Julie E Dalziel, Karl Fraser, Wayne Young, Catherine M Lloyd-West, Shalome A Bassett, Nicole C Roy
Altered gastric accommodation and intestinal morphology suggests impaired gastrointestinal (GI) transit may occur in the Wistar Kyoto (WKY) rat strain, as common in stress-associated functional GI disorders. Because changes in GI transit can alter microbiota composition, we investigated whether these are altered in WKY rats compared with the resilient Sprague Dawley (SD) rats under basal conditions, and characterized plasma lipid and metabolite differences. Bead transit was tracked by X-ray imaging to monitor: gastric emptying (GE; 4 h), small intestine (SI) transit (9 h) and large intestine transit (12 h)...
April 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28406702/an-alternatively-activated-macrophage-marker-cd163-in-severely-obese-patients-the-influence-of-very-low-calorie-diet-and-bariatric-surgery
#9
A Cinkajzlová, Z Lacinová, J Kloučková, P Kaválková, P Trachta, M Kosák, J Krátký, M Kasalický, K DoleŽalová, M Mráz, M Haluzík
CD163 is a marker of macrophages with anti-inflammatory properties and its soluble form (sCD163) is considered a prognostic predictor of several diseases including type 2 diabetes mellitus (T2DM). We explored sCD163 levels at baseline and after very low-calorie diet (VLCD) or bariatric surgery in 32 patients with obesity (20 undergoing VLCD and 12 bariatric surgery), 32 obese patients with T2DM (22 undergoing VLCD and 10 bariatric surgery), and 19 control subjects. We also assessed the changes of CD163 positive cells of monocyte-macrophage lineage in peripheral blood and subcutaneous adipose tissue (SAT) in subset of patients...
April 12, 2017: Physiological Research
https://www.readbyqxmd.com/read/28405305/metabolic-costs-of-capital-energy-storage-in-a-small-bodied-ectotherm
#10
Blaine D Griffen
Reproduction is energetically financed using strategies that fall along a continuum from animals that rely on stored energy acquired prior to reproduction (i.e., capital breeders) to those that rely on energy acquired during reproduction (i.e., income breeders). Energy storage incurs a metabolic cost. However, previous studies suggest that this cost may be minimal for small-bodied ectotherms. Here I test this assumption. I use a laboratory feeding experiment with the European green crab Carcinus maenas to establish individuals with different amounts of energy storage...
April 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28404824/glycolytic-inhibition-by-2-deoxy-d-glucose-abolishes-both-neuronal-and-network-bursts-in-an-in-vitro-seizure-model
#11
Li-Rong Shao, Carl E Stafstrom
Neuronal activity is energy demanding and coupled to cellular metabolism. In this study, we investigated the effects of glycolytic inhibition with 2-deoxy-D-glucose (2-DG) on basal membrane properties, spontaneous neuronal firing, and epileptiform network bursts in hippocampal slices. The effect of glycolytic inhibition on basal membrane properties was examined in hippocampal CA1 neurons, which are not ordinarily active spontaneously. Intracellular application of 2-DG did not significantly alter the membrane input resistance, action-potential threshold, firing pattern or input-output relationship of these neurons compared with simultaneously recorded neighboring neurons without intracellular 2-DG...
April 12, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28403937/glucocorticoids-modulate-human-brown-adipose-tissue-thermogenesis-in-vivo
#12
RANDOMIZED CONTROLLED TRIAL
Hannah Scotney, Michael E Symonds, James Law, Helen Budge, Don Sharkey, Konstantinos N Manolopoulos
INTRODUCTION: Brown adipose tissue (BAT) is a thermogenic organ with substantial metabolic capacity and has important roles in the maintenance of body weight and metabolism. Regulation of BAT is primarily mediated through the β-adrenoceptor (β-AR) pathway. The in vivo endocrine regulation of this pathway in humans is unknown. The objective of our study was to assess the in vivo BAT temperature responses to acute glucocorticoid administration. METHODS: We studied 8 healthy male volunteers, not pre-selected for BAT presence or activity and without prior BAT cold-activation, on two occasions, following an infusion with hydrocortisone (0...
May 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28402605/biotin-thiamine-responsive-basal-ganglia-disease-identification-of-a-pyruvate-peak-on-brain-spectroscopy-novel-mutation-in-slc19a3-and-calculation-of-prevalence-based-on-allele-frequencies-from-aggregated-next-generation-sequencing-data
#13
Carlos R Ferreira, Matthew T Whitehead, Eyby Leon
Biotin-thiamine responsive basal ganglia disease is an inborn error of metabolism caused by mutations in SLC19A3, encoding a transporter of thiamine across the plasma membrane. We report a novel mutation identified in the homozygous state in a patient with typical brain MRI changes. In addition, this patient had markedly elevated CSF pyruvate, a low lactate-to-pyruvate molar ratio, and an abnormal pyruvate peak at 2.4 ppm on brain magnetic resonance spectroscopy. Using aggregated exome sequencing data, we calculate the carrier frequency of mutations in SLC19A3 as 1 in 232 individuals in the general population, for an estimated prevalence of the disease of approximately 1 in 215,000 individuals...
April 12, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28401400/glucose-uptake-of-the-muscle-and-adipose-tissues-in-diabetes-and-obesity-disease-models-evaluation-of-insulin-and-%C3%AE-3-adrenergic-receptor-agonist-effects-by-18-f-fdg
#14
Seigo Ishino, Taku Sugita, Yusuke Kondo, Mika Okai, Kazue Tsuchimori, Masanori Watanabe, Ikuo Mori, Masaki Hosoya, Takashi Horiguchi, Hidenori Kamiguchi
OBJECTIVE: One of the major causes of diabetes and obesity is abnormality in glucose metabolism and glucose uptake in the muscle and adipose tissue based on an insufficient action of insulin. Therefore, many of the drug discovery programs are based on the concept of stimulating glucose uptake in these tissues. Improvement of glucose metabolism has been assessed based on blood parameters, but these merely reflect the systemic reaction to the drug administered. We have conducted basic studies to investigate the usefulness of glucose uptake measurement in various muscle and adipose tissues in pharmacological tests using disease-model animals...
April 11, 2017: Annals of Nuclear Medicine
https://www.readbyqxmd.com/read/28401293/how-low-can-you-go-an-adaptive-energetic-framework-for-interpreting-basal-metabolic-rate-variation-in-endotherms
#15
REVIEW
David L Swanson, Andrew E McKechnie, François Vézina
Adaptive explanations for both high and low body mass-independent basal metabolic rate (BMR) in endotherms are pervasive in evolutionary physiology, but arguments implying a direct adaptive benefit of high BMR are troublesome from an energetic standpoint. Here, we argue that conclusions about the adaptive benefit of BMR need to be interpreted, first and foremost, in terms of energetics, with particular attention to physiological traits on which natural selection is directly acting. We further argue from an energetic perspective that selection should always act to reduce BMR (i...
April 11, 2017: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
https://www.readbyqxmd.com/read/28397408/effect-of-oxygen-affinity-of-liposome-encapsulated-hemoglobin-on-cerebral-ischemia-and-reperfusion-as-detected-by-positron-emission-tomography-in-nonhuman-primates
#16
Akira T Kawaguchi, Mariko Yamano, Munetaka Haida, Hiroyuki Ohba, Takeharu Kakiuchi, Hideo Tsukada
We tested a hypothesis that liposome-encapsulated hemoglobin (LEH) with high oxygen (O2 ) affinity (h-LEH, P50 O2  = 10 mm Hg) may work better than LEH with low O2 affinity (l-LEH, P50 O2  = 40 mm Hg) in cerebral ischemia and reperfusion injury using positron emission tomography (PET) in primates undergoing middle cerebral artery (MCA) occlusion and reperfusion. Cerebral blood flow (CBF), O2 extract fraction (OEF), and cerebral metabolic rate of O2 (CMRO2 ) were successively determined by PET before ischemia, at 2 h of ischemia, immediately after reperfusion, and 3 h after reperfusion...
April 2017: Artificial Organs
https://www.readbyqxmd.com/read/28396201/pharmacological-but-not-genetic-alteration-of-neural-epo-modifies-the-co2-h-central-chemosensitivity-in-postnatal-mice
#17
Sofien Laouafa, Anne-Sophie Perrin-Terrin, Florine Jeton, Elizabeth Elliot-Portal, Rose Tam, Laurence Bodineau, Nicolas Voituron, Jorge Soliz
Cerebral erythropoietin (Epo) plays a crucial role for respiratory control in newborn rodents. We showed previously that soluble Epo receptor (sEpoR: an Epo antagonist) reduces basal ventilation and hypoxic hyperventilation at postnatal day 10 (P10) and in adult mice. However, at these ages (P10 and adulthood), Epo had no effect on central chemosensitivity. Nevertheless, it is known that the sensitivity to CO2/H(+) during the mammalian respiratory network maturation process is age-dependent. Accordingly, in this study we wanted to test the hypothesis that cerebral Epo is involved in the breathing stimulation induced by the activation of central CO2/H(+) chemoreceptors at earlier postnatal ages...
April 8, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28392796/spatiotemporal-transcriptome-analysis-provides-insights-into-bicolor-tepal-development-in-lilium-tiny-padhye
#18
Leifeng Xu, Panpan Yang, Yayan Feng, Hua Xu, Yuwei Cao, Yuchao Tang, Suxia Yuan, Xinyan Liu, Jun Ming
The bicolor Asiatic hybrid lily cultivar "Tiny Padhye" is an attractive variety because of its unique color pattern. During its bicolor tepal development, the upper tepals undergo a rapid color change from green to white, while the tepal bases change from green to purple. However, the molecular mechanisms underlying these changes remain largely uncharacterized. To systematically investigate the dynamics of the lily bicolor tepal transcriptome during development, we generated 15 RNA-seq libraries from the upper tepals (S2-U) and basal tepals (S1-D, S2-D, S3-D, and S4-D) of Lilium "Tiny Padhye...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28390265/acute-exposure-of-primary-rat-soleus-muscle-to-zilpaterol-hcl-%C3%AE-2-adrenergic-agonist-tnf%C3%AE-or-il-6-in-culture-increases-glucose-oxidation-rates-independent-of-the-impact-on-insulin-signaling-or-glucose-uptake
#19
Caitlin N Cadaret, Kristin A Beede, Hannah E Riley, Dustin T Yates
Recent studies show that adrenergic agonists and inflammatory cytokines can stimulate skeletal muscle glucose uptake, but it is unclear if glucose oxidation is similarly increased. Thus, the objective of this study was to determine the effects of ractopamine HCl (β1 agonist), zilpaterol HCl (β2 agonist), TNFα, and IL-6 on glucose uptake and oxidation rates in unstimulated and insulin-stimulated soleus muscle strips from adult Sprague-Dawley rats. Effects on phosphorylation of Akt (phospho-Akt), p38 MAPK (phospho-p38), and p44/42 MAPK (phospho-p44/42) was also determined...
April 5, 2017: Cytokine
https://www.readbyqxmd.com/read/28389215/clock-gene-dysregulation-induced-by-chronic-er-stress-disrupts-%C3%AE-cell-function
#20
Yasuharu Ohta, Akihiko Taguchi, Takuro Matsumura, Hiroko Nakabayashi, Masaru Akiyama, Kaoru Yamamoto, Ruriko Fujimoto, Risa Suetomi, Akie Yanai, Koh Shinoda, Yukio Tanizawa
In Wfs1(-/-)A(y)/a islets, in association with endoplasmic reticulum (ER) stress, D-site-binding protein (Dbp) expression decreased and Nuclear Factor IL-3 (Nfil3)/E4 Promoter-binding protein 4 (E4bp4) expression increased, leading to reduced DBP transcriptional activity. Similar alterations were observed with chemically-induced ER stress. Transgenic mice expressing E4BP4 under the control of the mouse insulin I gene promoter (MIP), in which E4BP4 in β-cells is expected to compete with DBP for D-box, displayed remarkable glucose intolerance with severely impaired insulin secretion...
March 30, 2017: EBioMedicine
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