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https://www.readbyqxmd.com/read/28528772/early-interleukin-6-enhances-hepatic-ketogenesis-in-appswe-psen1de9-mice-via-3-hydroxy-3-methylglutary-coa-synthase-2-signaling-activation-by-p38-nuclear-factor-%C3%AE%C2%BAb-p65
#1
Le Shi, Daina Zhao, Chen Hou, Yunhua Peng, Jing Liu, Shuangxi Zhang, Jiankang Liu, Jiangang Long
Alzheimer's disease (AD) is considered a multifactorial disease that affects the central nervous system and periphery. A decline in brain glucose metabolism is an early feature of AD and is accompanied by a phenotypic shift from aerobic glycolysis to ketogenesis. The liver is responsible for the generation of the ketone body. However, the mechanism that underlies hepatic ketogenesis in AD remains unclear. Here, we investigated hepatic ketogenesis during the early stage of AD pathogenesis in amyloid precursor protein (APPSWE) and presenilin (PSEN1dE9) (APP/PS1) mice...
April 26, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28512002/cell-surface-g-protein-coupled-receptors-for-tumor-associated-metabolites-a-direct-link-to-mitochondrial-dysfunction-in-cancer
#2
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/28506519/sodium-glucose-co-transporters-and-their-inhibition-clinical-physiology
#3
REVIEW
Ele Ferrannini
Sodium-glucose cotransporter-2 (SGLT2) is selectively expressed in the human kidney, where it executes reabsorption of filtered glucose with a high capacity; it may be overactive in patients with diabetes, especially in the early, hyperfiltering stage of the disease. As a therapeutic target, SGLT2 has been successfully engaged by orally active, selective agents. Initially developed as antihyperglycemic drugs, SGLT2 inhibitors have deployed a range of in vivo actions. Consequences of their primary effect, i...
May 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28468827/hmg-coa-synthase-1-is-a-synthetic-lethal-partner-of-braf-v600e-in-human-cancers
#4
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/28462983/alterations-in-metabolic-patterns-have-a-key-role-in-diagnosis-and-progression-of-primrose-syndrome
#5
Alberto Casertano, Paolo Fontana, Raoul C Hennekam, Marco Tartaglia, Rita Genesio, Tina Barbaro Dieber, Lucia Ortega, Lucio Nitsch, Daniela Melis
Primrose syndrome is characterized by unusual facial features, macrocephaly, intellectual disability, enlarged, and calcified external ears, sparse body hair, and distal muscle wasting. Nine patients have been described in the literature. The disorder is due to missense mutations in ZBTB20. Here we describe one newly diagnosed 18-month-old patient and provide 10 year follow-up of an earlier reported patient, highlighting the progression and complexity of the disorder. Metabolic studies showed reduced glucose tolerance with prevalence of amino acids and fatty acids catabolism, ketogenesis, and gluconeogenesis, resulting in a Krebs cycle reversion...
April 30, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28462693/sarcopenia-in-patients-with-advanced-liver-disease
#6
Francesca Romana Ponziani, Antonio Gasbarrini
Sarcopenia is the loss of muscle mass and function, affecting up to 70% of patients with advanced liver disease. Liver cirrhosis is characterized by an altered glucose metabolism, lipid oxidation, ketogenesis and protein catabolism, leading to the loss of adipose and muscle tissue. The gastrointestinal dysfunction of cirrhotic patients results in inadequate nutrients intake and is responsible for muscle weakness thus limiting physical exercise and perpetuating the reduction of muscle mass. Recently, alterations of hormonal pathways involved in muscle growth, increased intestinal permeability and changes in the gut microbiota composition have been reported in cirrhotic patients...
April 28, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28450882/oral-%C3%AE-hydroxybutyrate-increases-ketonemia-decreases-visceral-adipocyte-volume-and-improves-serum-lipid-profile-in-wistar-rats
#7
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/28447390/high-non-esterified-fatty-acid-concentrations-promote-expression-and-secretion-of-fibroblast-growth-factor-21-in-calf-hepatocytes-cultured-in-vitro
#8
J G Wang, Y Z Guo, Y Z Kong, S Dai, B Y Zhao
Negative energy balance is considered as the pathological basis of energy metabolic disorders in periparturient dairy cows. Serum non-esterified fatty acids (NEFA) are one of the most important indicators of energy balance status. Fibroblast growth factor 21 (FGF21) has been identified as a hepatokine involved in regulation of metabolic adaptations, such as promoting hepatic lipid oxidation and ketogenesis, during energy deprivation. However, the direct effects of NEFA on FGF21 expression and secretion in bovine hepatocytes are not entirely clear...
April 26, 2017: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/28428362/hepatic-lipid-accumulation-cause-and-consequence-of-dysregulated-glucoregulatory-hormones
#9
Caroline E Geisler, Benjamin Jennings Renquist
Fatty liver can be diet, endocrine, genetic, viral, or drug induced. Independent of cause, hepatic lipid accumulation promotes systemic metabolic dysfunction. By acting as peroxisome proliferator activated receptor (PPAR) ligands, hepatic non-esterified fatty acids upregulate expression of gluconeogenic, beta-oxidative, lipogenic, and ketogenic genes, promoting hyperglycemia, hyperlipidemia, and ketosis. The typical hormonal environment in fatty liver disease consists of hyperinsulinemia, hyperglucagonemia, hypercortisolemia, growth hormone deficiency, and elevated sympathetic tone...
April 20, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28414295/high-salt-intake-reprioritizes-osmolyte-and-energy-metabolism-for-body-fluid-conservation
#10
Kento Kitada, Steffen Daub, Yahua Zhang, Janet D Klein, Daisuke Nakano, Tetyana Pedchenko, Louise Lantier, Lauren M LaRocque, Adriana Marton, Patrick Neubert, Agnes Schröder, Natalia Rakova, Jonathan Jantsch, Anna E Dikalova, Sergey I Dikalov, David G Harrison, Dominik N Müller, Akira Nishiyama, Manfred Rauh, Raymond C Harris, Friedrich C Luft, David H Wassermann, Jeff M Sands, Jens Titze
Natriuretic regulation of extracellular fluid volume homeostasis includes suppression of the renin-angiotensin-aldosterone system, pressure natriuresis, and reduced renal nerve activity, actions that concomitantly increase urinary Na+ excretion and lead to increased urine volume. The resulting natriuresis-driven diuretic water loss is assumed to control the extracellular volume. Here, we have demonstrated that urine concentration, and therefore regulation of water conservation, is an important control system for urine formation and extracellular volume homeostasis in mice and humans across various levels of salt intake...
May 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28412387/germ-cells-regulate-3-hydroxybutyrate-production-in-rat-sertoli-cells
#11
Mariana Regueira, Gustavo Marcelo Rindone, María Noel Galardo, Eliana Herminia Pellizzari, Selva Beatriz Cigorraga, Silvina Beatriz Meroni, María Fernanda Riera
Paracrine regulation of Sertoli cell function by germ cells is an outstanding characteristic of testicular physiology. It has been demonstrated that Sertoli cells produce ketone bodies and that germ cells may use them as energy source. The aim of the study was to analyze a possible regulation by germ cells of ketogenesis in Sertoli cells. Cultures of Sertoli cells (SC) obtained from 31-day-old rats were co-cultured with germ cells (GC). The results presented herein show that the presence of GC stimulated 3-hydroxybutyrate production and increased mRNA levels of two enzymes involved in ketogenesis-carnitine palmitoyltransferase 1a (CPT1a) and mitochondrial 3-hydroxy-3-methylglutaryl-CoA (mHMGCoA) synthase- in SC...
April 12, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28396157/coupled-brain-and-urine-spectroscopy-in-vivo-metabolomic-characterization-of-hmg-coa-lyase-deficiency-in-5-patients
#12
Dominique Roland, Patrice Jissendi-Tchofo, Gilbert Briand, Joseph Vamecq, Monique Fontaine, Vincent Ultré, Cécile Acquaviva-Bourdain, Karine Mention, Dries Dobbelaere
BACKGROUND: 3-Hydroxy-3-Methylglutaryl-Coenzyme A (HMG-CoA) lyase deficiency is a rare inborn error of leucine metabolism and ketogenesis. Despite recurrent hypoglycemia and metabolic decompensations, most patients have a good clinical and neurological outcome contrasting with abnormal brain magnetic resonance imaging (MRI) signals and consistent abnormal brain proton magnetic resonance spectroscopy ((1)H-MRS) metabolite peaks. Identifying these metabolites could provide surrogate markers of the disease and improve understanding of MRI-clinical discrepancy and follow-up of affected patients...
March 30, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28381467/hepatic-ketogenesis-induced-by-middle-cerebral-artery-occlusion-in-mice
#13
Konrad Koch, Dirk Berressem, Jan Konietzka, Anna Thinnes, Gunter P Eckert, Jochen Klein
BACKGROUND: Ketone bodies are known to substitute for glucose as brain fuel when glucose availability is low. Ketogenic diets have been described as neuroprotective. Similar data have been reported for triheptanoin, a fatty oil and anaplerotic compound. In this study, we monitored the changes of energy metabolites in liver, blood, and brain after transient brain ischemia to test for ketone body formation induced by experimental stroke. METHODS AND RESULTS: Mice were fed a standard carbohydrate-rich diet or 2 fat-rich diets, 1 enriched in triheptanoin and 1 in soybean oil...
April 5, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28325783/renal-handling-of-ketones-in-response-to-sodium-glucose-cotransporter-2-inhibition-in-patients-with-type-2-diabetes
#14
Ele Ferrannini, Simona Baldi, Silvia Frascerra, Brenno Astiarraga, Elisabetta Barsotti, Aldo Clerico, Elza Muscelli
OBJECTIVE: Pharmacologically induced glycosuria elicits adaptive responses in glucose homeostasis and hormone release, including decrements in plasma glucose and insulin levels, increments in glucagon release, enhanced lipolysis, and stimulation of ketogenesis, resulting in an increase in ketonemia. We aimed at assessing the renal response to these changes. RESEARCH DESIGN AND METHODS: We measured fasting and postmeal urinary excretion of glucose, β-hydroxybutyrate (β-HB), lactate, and sodium in 66 previously reported patients with type 2 diabetes and preserved renal function (estimated glomerular filtration rate ≥60 mL · min(-1) · 1...
March 21, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28323955/rapid-onset-of-diabetic-ketoacidosis-after-sglt2-inhibition-in-a-patient-with-unrecognized-acromegaly
#15
Marino Quarella, Daniel Walser, Michael Brändle, Jean-Yves Fournier, Stefan Bilz
Context: Diabetic ketoacidosis has been described as a rare complication of acromegaly and may be observed in 1% of affected patients. The well-described direct lipolytic effect of growth hormone results in increased availability of free fatty acids (FFAs) for hepatic ketogenesis and is an important pathogenic event. More recently, ketoacidosis has been identified as an important complication of sodium-glucose-transport-protein 2 inhibitors (SGLT2i). Increased pancreatic glucagon secretion, impaired renal ketone body clearance, and an increase in FFA concentrations secondary to decreased insulin concentrations are likely precipitating factors...
May 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28320515/hmgcs2-promotes-autophagic-degradation-of-the-amyloid-%C3%AE-precursor-protein-through-ketone-body-mediated-mechanisms
#16
Li-Tian Hu, Bing-Lin Zhu, Yu-Jie Lai, Yan Long, Jing-Si Zha, Xiao-Tong Hu, John H Zhang, Guo-Jun Chen
HMGCS2 (mitochondrial 3-hydroxy-3-methylglutaryl-COA synthase 2) is a control enzyme in ketogenesis. The mitochondrial localization and interaction with APP (β-amyloid precursor protein) suggest that HMGCS2 may play a role in the pathophysiology of AD (Alzheimer's disease). Here we report that overexpression of HMGCS2 decreased levels of APP and related CTFs (carboxy-terminal fragments), which was largely prevented by an autophagic inhibitor chloroquine. In addition, HMGCS2 enhancement of autophagic marker LC3II was diminished by rapamycin, an inhibitor of mechanistic target of rapamycin...
March 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28304146/liraglutide-acutely-suppresses-glucagon-lipolysis-and-ketogenesis-in-type-1-diabetes
#17
Manisha Garg, Husam Ghanim, Nitesh D Kuhadiya, Kelly Green, Jeanne Hejna, Sanaa Abuaysheh, Barrett Torre, Manav Batra, Antoine Makdissi, Ajay Chaudhuri, Paresh Dandona
In view of the occurrence of diabetic ketoacidosis associated with the use of sodium-glucose transport protein-2 (SGLT2) inhibitors in patients with type 1 diabetes (T1DM) and the relative absence of this complication in patients treated with liraglutide in spite of reductions in insulin doses, we investigated the effect of liraglutide on ketogenesis. Twenty-six patients with inadequately controlled T1DM were randomly divided into two groups of 13 patients each. After an overnight fast, patients were injected, subcutaneously, with either liraglutide 1...
March 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28303514/euglycemic-ketosis-in-patients-with-type-2-diabetes-on-sglt2-inhibitor-therapy-an-emerging-problem-and-solutions-offered-by-diabetes-technology
#18
A Pfützner, D Klonoff, L Heinemann, N Ejskjaer, J Pickup
Diabetic ketoacidosis is an infrequent but life-threatening acute complication of diabetes, affecting predominantly patients with type 1 diabetes, children, and pregnant women, where ketosis is usually associated with marked hyperglycemia. Recently, an increasing number of cases have been reported of euglycemic diabetic ketoacidosis in patients with type 2 diabetes receiving sodium-glucose cotransporter 2 inhibitor treatment in routine practice. There is a minor, but not negligible diabetic ketoacidosis risk associated with this drug class, which was not seen in randomized clinical trials...
April 2017: Endocrine
https://www.readbyqxmd.com/read/28302729/phagocytosis-dependent-ketogenesis-in-retinal-pigment-epithelium
#19
Juan Reyes-Reveles, Anuradha Dhingra, Desiree Alexander, Alvina Bragin, Nancy J Philp, Kathleen Boesze-Battaglia
Daily, the retinal pigment epithelium (RPE) ingests a bolus of lipid and protein in the form of phagocytized photoreceptor outer segments (OS). The RPE, like the liver, expresses enzymes required for fatty acid oxidation and ketogenesis. This suggests that these pathways play a role in the disposal of lipids from ingested OS, as well as providing a mechanism for recycling metabolic intermediates back to the outer retina. In this study, we examined whether OS phagocytosis was linked to ketogenesis. We found increased levels of β-hydroxybutyrate (β-HB) in the apical medium following ingestion of OS by human fetal RPE and ARPE19 cells cultured on Transwell inserts...
May 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28249286/impact-of-fibroblast-growth-factors-19-and-21-in-bariatric-metabolism
#20
REVIEW
Ashley Patton, Farooq H Khan, Rohit Kohli
BACKGROUND: Bariatric surgery is a popular and effective therapeutic intervention for obesity, which is an abnormal health condition that is prevalent worldwide. Metabolic improvements that precede weight loss after bariatric surgery may be mediated, in part, through the fibroblast growth factor (FGF) 15/19 and FGF21 signaling pathways. Both FGF15/19 and FGF21 are hormone-like members of the FGF family and exert their metabolic effects in an endocrine manner. Enhanced bile acid recycling after bariatric surgery leads to increased circulating levels of FGF15/19 in the distal small intestine...
2017: Digestive Diseases
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