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Ketone bodies

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https://www.readbyqxmd.com/read/28526997/nafld-as-a-sexual-dimorphic-disease-role-of-gender-and-reproductive-status-in-the-development-and-progression-of-nonalcoholic-fatty-liver-disease-and-inherent-cardiovascular-risk
#1
REVIEW
Stefano Ballestri, Fabio Nascimbeni, Enrica Baldelli, Alessandra Marrazzo, Dante Romagnoli, Amedeo Lonardo
Nonalcoholic fatty liver disease (NAFLD) spans steatosis through nonalcoholic steatohepatis, cirrhosis, and hepatocellular carcinoma (HCC) associated with striking systemic features and excess cardiovascular and liver-related mortality. The pathogenesis of NAFLD is complex and multifactorial. Endocrine derangements are closely linked with dysmetabolic traits. For example, in animal and human studies, female sex is protected from dysmetabolism thanks to young individuals' ability to partition fatty acids towards ketone body production rather than very low density lipoprotein (VLDL)-triacylglycerol, and to sex-specific browning of white adipose tissue...
May 19, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28521671/the-anticonvulsant-effects-of-ketogenic-diet-on%C3%A2-epileptic-seizures-and-potential-mechanisms
#2
Yifan Zhang, Jingwei Xu, Yingchao Zhang, Wei Yang, Bingjin Li
Epilepsy is one of the most commonly diagnosed neurologic disorders with characteristics of epileptic seizures. Although the multitude of anticonvulsant drugs has been developed, recurrent epileptic seizures remain intractable and contribute to the serious morbidity worldwide. Recently, increasing studies have established the beneficial effects of ketogenic diet (KD) on epileptic seizure reduction. Both basic experiments and clinical trials demonstrated that KD significantly reduced seizure frequency with mild adverse effects...
May 17, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28514599/a-bioenergetics-systems-evaluation-of-ketogenic-diet-liver-effects
#3
Lewis J Hutfles, Heather M Wilkins, Scott J Koppel, Ian W Weidling, J Eva Selfridge, Eephie Tan, John P Thyfault, Chad Slawson, Aron W Fenton, Hao Zhu, Russell H Swerdlow
Ketogenic diets induce hepatocyte fatty acid oxidation and ketone body production. To further evaluate how ketogenic diets affect hepatocyte bioenergetic infrastructure, we analyzed livers from C57Bl/6J male mice maintained for one month on a ketogenic or standard chow diet. Compared to the standard diet, the ketogenic diet increased cytosolic and mitochondrial protein acetylation and also altered protein succinylation patterns. SIRT3 protein decreased while SIRT5 protein increased, and gluconeogenesis, oxidative phosphorylation, and mitochondrial biogenesis pathway proteins were variably and likely strategically altered...
May 17, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28512002/cell-surface-g-protein-coupled-receptors-for-tumor-associated-metabolites-a-direct-link-to-mitochondrial-dysfunction-in-cancer
#4
REVIEW
Bojana Ristic, Yangzom D Bhutia, Vadivel Ganapathy
Mitochondria are the sites of pyruvate oxidation, citric acid cycle, oxidative phosphorylation, ketogenesis, and fatty acid oxidation. Attenuation of mitochondrial function is one of the most significant changes that occurs in tumor cells, directly linked to oncogenesis, angiogenesis, Warburg effect, and epigenetics. In particular, three mitochondrial enzymes are inactivated in cancer: pyruvate dehydrogenase (PDH), succinate dehydrogenase (SDH), and 3-hydroxy-3-methylglutaryl CoA synthase-2 (HMGCS2). These enzymes are subject to regulation via acetylation/deacetylation...
May 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28510035/ketone-bodies-as-a-possible-adjuvant-to-ketogenic-diet-in-pdhc-deficiency-but-not-in-glut1-deficiency
#5
F Habarou, N Bahi-Buisson, E Lebigot, C Pontoizeau, M T Abi-Warde, A Brassier, K H Le Quan Sang, C Broissand, S Vuillaumier-Barrot, A Roubertie, A Boutron, C Ottolenghi, P de Lonlay
OBJECTIVE: Ketogenic diet is the first line therapy for neurological symptoms associated with pyruvate dehydrogenase deficiency (PDHD) and intractable seizures in a number of disorders, including GLUT1 deficiency syndrome (GLUT1-DS). Because high-fat diet raises serious compliance issues, we investigated if oral L,D-3-hydroxybutyrate administration could be as effective as ketogenic diet in PDHD and GLUT1-DS. METHODS: We designed a partial or total progressive substitution of KD with L,D-3-hydroxybutyrate in three GLUT1-DS and two PDHD patients...
May 17, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28502807/augmenting-brain-metabolism-to-increase-macro-and-chaperone-mediated-autophagy-for-decreasing-neuronal-proteotoxicity-and-aging
#6
REVIEW
Ben Loos, Daniel J Klionsky, Esther Wong
Accumulation of toxic protein aggregates in the nerve cells is a hallmark of neuronal diseases and brain aging. Mechanisms to enhance neuronal surveillance to improve neuronal proteostasis have a direct impact on promoting neuronal health and forestalling age-related decline in brain function. Autophagy is a lysosomal degradative pathway pivotal for neuronal protein quality control. Different types of autophagic mechanisms participate in protein handling in neurons. Macroautophagy targets misfolded and aggregated proteins in autophagic vesicles to the lysosomes for destruction, while chaperone-mediated autophagy (CMA) degrades specific soluble cytosolic proteins delivered to the lysosomes by chaperones...
May 11, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28496348/role-of-sodium-glucose-cotransporter-2-inhibitors-in-type-i-diabetes-mellitus
#7
REVIEW
Hala Ahmadieh, Nisrine Ghazal, Sami T Azar
The burden of diabetes mellitus (DM) in general has been extensively increasing over the past few years. Selective sodium glucose cotransporter-2 (SGLT2) inhibitors were extensively studied in type 2 DM and found to have sustained urinary glucose loss, improvement of glycemic control, in addition to their proven metabolic effects on weight, blood pressure, and cardiovascular benefits. Type 1 DM (T1D) patients clearly depend on insulin therapy, which till today fails to achieve the optimal glycemic control and metabolic targets that are needed to prevent risk of complications...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28488182/successful-management-of-pregnancies-in-patients-with-inherited-disorders-of-ketone-body-metabolism
#8
Raashda Ainuddin Sulaiman, Maha Al-Nemer, Rubina Khan, Munirah Almasned, Bedour S Handoum, Zuhair N Al-Hassnan
Patients with succinyl-CoA:3-oxoacid CoA transferase (SCOT) deficiency and 3-hydroxy-3-methylglutaryl (HMG)-CoA lyase deficiency are at increased risk of developing metabolic acidosis and hypoglycemia during pregnancy, delivery, and postpartum period. This can be fatal if not treated appropriately. Pregnancy in such patients should be managed in a specialist center by a multidisciplinary team including metabolic physician, high-risk obstetrician, and metabolic dietician. We report two pregnancies in women with SCOT deficiency and HMG-CoA lyase deficiency, which were successfully managed at this tertiary care center...
May 10, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28486923/kynurenic-acid-and-neuroprotective-activity-of-the-ketogenic-diet-in-the-eye
#9
Tomasz Żarnowski, Maria Tulidowicz-Bielak, Iwona Żarnowska, Krystyna Mitosek-Szewczyk, Artur Wnorowski, Krzysztof Jóźwiak, Maciej Gasior, Waldemar A Turski
There is growing evidence of the involvement of the kynurenine metabolic pathway and the enhancement of kynurenic acid (KYNA) production in the neuroprotective effects of the ketogenic diet (KD). KD and ketone bodies (KBs) that are elevated during exposure to the KD each have a neuroprotective effect on retinal ganglion cells in a rat model of N-methyl-D-aspartate (NMDA)-induced neuronal damage. Chronic exposure to KD also increases KYNA concentrations in discrete rat brain structures. A non-selective glutamate receptor agonist, glutamate, also decreases the production of KYNA in bovine retinal slices; this effect is attenuated by acetoacetate and β-hydroxybutyrate, two of three KBs overproduced during KD...
May 9, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28483672/acetoacetate-is-a-more-efficient-energy-yielding-substrate-for-human-mesenchymal-stem-cells-than-glucose-and-generates-fewer-reactive-oxygen-species
#10
Mary Board, Colleen Lopez, Christian van den Bos, Richard Callaghan, Kieran Clarke, Carolyn Carr
Stem cells have been assumed to demonstrate a reliance on anaerobic energy generation, suited to their hypoxic in vivo environment. However, we found that human mesenchymal stem cells (hMSCs) have an active oxidative metabolism with a range of substrates. More ATP was consistently produced from substrate oxidation than glycolysis by cultured hMSCs. Strong substrate preferences were shown with the ketone body, acetoacetate, being oxidised at up to 35 times the rate of glucose. ROS-generation was 45-fold lower during acetoacetate oxidation compared with glucose and substrate preference may be an adaptation to reduce oxidative stress...
May 5, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28482939/daytime-restricted-feeding-modifies-the-daily-regulation-of-fatty-acid-%C3%AE-oxidation-and-the-lipoprotein-profile-in-rats
#11
J B Rivera-Zavala, C Molina-Aguilar, M Pérez-Mendoza, M Olguín-Martínez, R Hernández-Muñoz, G A Báez-Ruiz, M Díaz-Muñoz
Daytime restricted feeding (2 h of food access from 12.00 to 14.00 hours for 3 weeks) is an experimental protocol that modifies the relationship between metabolic networks and the circadian molecular clock. The precise anatomical locus that controls the biochemical and physiological adaptations to optimise nutrient use is unknown. We explored the changes in liver oxidative lipid handling, such as β-oxidation and its regulation, as well as adaptations in the lipoprotein profile. It was found that daytime restricted feeding promoted an elevation of circulating ketone bodies before mealtime, an altered hepatic daily rhythmicity of 14CO2 production from radioactive palmitic acid, and an up-regulation of the fatty acid oxidation activators, the α-subunit of AMP-activated protein kinase (AMPK), the deacetylase silent mating type information regulation homolog 1, and the transcriptional factor PPARγ-1α coactivator...
May 9, 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28482601/functionalized-biocompatible-and-impermeable-nanoscale-coatings-for-peek
#12
Firas Awaja, Pieter Cools, Birgit Lohberger, Anton Yu Nikiforov, Giorgio Speranza, Rino Morent
Biologically compatible coatings that provide hermetic seal could resolve a major technological hurdle in the attempt to replace metals with polymers for biochips and active medical implants. The use of amorphous carbon/diamond like carbon (a-C:H) coatings to hermetically seal and biologically enhance polyether-ether-ketone (PEEK) for biomedical device integration in the human body was investigated. The PEEK coating functionality (sp3/sp2 ratio), hardness and thickness (70-200nm) were controlled, by varying H2 and N2 concentration during the plasma operation with CH4...
July 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28473603/increased-hepatic-mitochondrial-fa-oxidation-leads-to-lower-tg-levels-in-rat-liver-and-plasma-and-is-associated-with-upregulation-of-uncoupling-proteins-and-downregulation-of-apolipoprotein-c-iii
#13
Carine Lindquist, Bodil Bjørndal, Christine Renate Rossmann, Deusdedit Tusubira, Asbjørn Svardal, Gro Vatne Røsland, Karl Johan Tronstad, Seth Hallström, Rolf Kristian Berge
Hepatic mitochondrial function, APOC-III and LPL are potential targets for TG lowering drugs. After three weeks of dietary treatment with the compound 2-(tridec-12 -yn-1-ylthio) acetic acid (1-triple TTA), the hepatic mitochondrial FA oxidation increased more than 5-fold in male Wistar rats. Gene expression analysis in liver showed significant downregulation of APOC-III, and upregulation of LPL and the VLDL receptor. This led to lower hepatic (53 %) and plasma (73 %) TG levels. Concomitantly liver-specific biomarkers related to mitochondrial biogenesis and function (mitochondrial DNA, citrate synthase activity and cytochrome c and Tfam gene expression) were elevated...
May 4, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28473467/hepatic-protein-phosphatase-1-regulatory-subunit-3b-ppp1r3b-promotes-hepatic-glycogen-synthesis-and-thereby-regulates-fasting-energy-homeostasis
#14
Minal B Mehta, Swapnil V Shewale, Raymond N Sequeira, John S Millar, Nicholas J Hand, Daniel J Rader
Maintenance of whole-body glucose homeostasis is critical to glycemic function. Genetic variants mapping to chromosome 8p23.1 in genome-wide association studies have been linked to glycemic traits in humans. The gene of known function closest to the mapped region, PPP1R3B (protein phosphatase 1 regulatory subunit 3B), encodes a protein (GL) that regulates glycogen metabolism in the liver. We therefore sought to test the hypothesis that hepatic PPP1R3B is associated with glycemic traits. We generated mice with either liver-specific deletion (Ppp1r3bΔhep) or liver-specific overexpression of Ppp1r3b...
May 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28468827/hmg-coa-synthase-1-is-a-synthetic-lethal-partner-of-braf-v600e-in-human-cancers
#15
Liang Zhao, Jun Fan, Siyuan Xia, Yaozhu Pan, Shuangping Liu, Guoqing Qian, Zhiyu Qian, Hee-Bum Kang, Jack L Arbiser, Brian P Pollack, Ragini Kudchadkar, David H Lawson, Michael Rossi, Omar Abdel-Wahab, Taha Merghoub, Hanna J Khoury, Fadlo R Khuri, Lawrence H Boise, Sagar Lonial, Fangping Chen, Jing Chen, Ruiting Lin
Contributions of metabolic changes to cancer development and maintenance have received increasing attention in recent years. Although many human cancers share similar metabolic alterations, it remains unclear whether oncogene-specific metabolic alterations are required for tumor development. Using RNAi-based screen targeting the majority of the known metabolic proteins, we recently found that oncogenic BRAF(V600E) upregulates HMG-CoA lyase (HMGCL), which converts HMG-CoA to acetyl-CoA and a ketone body, acetoacetate, that selectively enhances BRAFV600E-dependent MEK1 activation in human cancer...
May 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28452030/the-effects-and-the-toxicity-increases-caused-by-bicarbonate-chloride-and-other-water-components-during-the-uv-tio2-degradation-of-oxazaphosphorine-drugs
#16
Webber Wei-Po Lai, Ying-Chih Chuang, Angela Yu-Chen Lin
The influences of HCO3(-), Cl(-), and other components on the UV/TiO2 degradation of the antineoplastic agents ifosfamide (IFO) and cyclophosphamide (CP) were studied in this work. The results indicated that the presence of HCO3(-), Cl(-), NO3(-), and SO4(2-) in water bodies resulted in lower degradation efficiencies. The half-lives of IFO and CP were 1.2 and 1.1 min and increased 2.3-7.3 and 3.2-6.3 times, respectively, in the presence of the four anions (initial compound concentration = 100 μg/L, TiO2 loading =100 mg/L, anion concentration = 1000 mg/L, and pH = 8)...
April 27, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28450882/oral-%C3%AE-hydroxybutyrate-increases-ketonemia-decreases-visceral-adipocyte-volume-and-improves-serum-lipid-profile-in-wistar-rats
#17
Rennan de Oliveira Caminhotto, Ayumi Cristina Medeiros Komino, Flaviane de Fatima Silva, Sandra Andreotti, Rogério Antônio Laurato Sertié, Gabriela Boltes Reis, Fabio Bessa Lima
BACKGROUND: Ketosis can be induced in humans and in animals by fasting or dietary interventions, such as ketogenic diets. However, the increasing interest on the ketogenic state has motivated the development of alternative approaches to rapidly increase ketonemia using less drastic interventions. Here, it was tested whether oral intake of a β-hydroxybutyrate (βHB) mineral salt mixture could increase ketonemia in Wistar rats without any other dietary changes, thereby being a useful model to study ketones effects alone on metabolism...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28446244/ketogenic-diet-in-the-treatment-of-epilepsy-in-children-under-the-age-of-2-years-study-protocol-for-a-randomised-controlled-trial
#18
Siobhan Titre-Johnson, Natasha Schoeler, Christin Eltze, Ruth Williams, Katharina Vezyroglou, Helen McCullagh, Nick Freemantle, Simon Heales, Rachel Kneen, Louise Marston, Tim Martland, Irwin Nazareth, Elizabeth Neal, Andrew Lux, Alasdair Parker, Shakti Agrawal, Penny Fallon, J Helen Cross
BACKGROUND: The incidence of epilepsy is greatest in the first 2 years of life, an age group where there is generally a poor prognosis for both seizure control and neurodevelopmental outcome. Early control of seizures can be associated with better developmental outcome but many of the epilepsies presenting in infancy are poorly responsive to antiepileptic medication. The ketogenic diet (KD) is a high-fat, low-carbohydrate diet designed to mimic the effects of starvation on the body. Dietary fat is converted into ketones in the body and used as an energy source by the brain...
April 26, 2017: Trials
https://www.readbyqxmd.com/read/28433617/induced-and-controlled-dietary-ketosis-as-a-regulator-of-obesity-and-metabolic-syndrome-pathologies
#19
Madeline K Gibas, Kelly J Gibas
A worsening epidemic of diabetes and its precursor, metabolic syndrome (MetS) is engulfing America. A healthy individual, with proper glucose regulation has an ability to switch between burning fat and carbohydrates. It has been suggested that signaling errors within this homeostatic system, characterized by impaired switching of substrate oxidation from glucose to fat in response to insulin, can contribute to the etiology of metabolic syndrome and occurs before the development of type II diabetes. Glucose regulation with restored insulin sensitivity facilitated through clinically regulated, benign dietary ketosis (BDK), may significantly reduce, regulate and reverse the adverse pathologies common to MetS and obesity...
March 28, 2017: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/28414904/in-silico-prediction-of-chemicals-binding-to-aromatase-with-machine-learning-methods
#20
Hanwen Du, Yingchun Cai, Hongbin Yang, Hongxiao Zhang, Yuhan Xue, Guixia Liu, Yun Tang, Weihua Li
Environmental chemicals may affect endocrine systems through multiple mechanisms, one of which is via effects on aromatase (also known as CYP19A1), an enzyme critical for maintaining the normal balance of estrogens and androgens in the body. Therefore, rapid and efficient identification of aromatase-related endocrine disrupting chemicals (EDCs) is important for toxicology and environment risk assessment. In this study, on the basis of the Tox21 10K compound library, in silico classification models for predicting aromatase binders/nonbinders were constructed by machine learning methods...
April 26, 2017: Chemical Research in Toxicology
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