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Ketogenesis

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https://www.readbyqxmd.com/read/28931870/inactivation-of-hmgcl-promotes-proliferation-and-metastasis-of-nasopharyngeal-carcinoma-by-suppressing-oxidative-stress
#1
Wenqi Luo, Liting Qin, Bo Li, Zhipeng Liao, Jiezhen Liang, Xiling Xiao, Xue Xiao, Yingxi Mo, Guangwu Huang, Zhe Zhang, Xiaoying Zhou, Ping Li
Altered metabolism is considered as a hallmark of cancer. Here we investigated expression of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) 2 lyase (HMGCL), an essential enzyme in ketogenesis, which produces ketone bodies by the breakdown of fatty acids to supply energy, in nasopharyngeal carcinoma (NPC). The expression of HMGCL was silenced in NPC tissue. Downregulation of HMGCL in NPC was associated with low intracellular β-hydroxybutyrate (β-HB) production, thereby reducing reactive oxygen species (ROS) generation...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899914/military-training-elicits-marked-increases-in-plasma-metabolomic-signatures-of-energy-metabolism-lipolysis-fatty-acid-oxidation-and-ketogenesis
#2
J Philip Karl, Lee M Margolis, Nancy E Murphy, Christopher T Carrigan, John W Castellani, Elisabeth H Madslien, Hilde-Kristin Teien, Svein Martini, Scott J Montain, Stefan M Pasiakos
Military training studies provide unique insight into metabolic responses to extreme physiologic stress induced by multiple stressor environments, and the impacts of nutrition in mediating these responses. Advances in metabolomics have provided new approaches for extending current understanding of factors modulating dynamic metabolic responses in these environments. In this study, whole-body metabolic responses to strenuous military training were explored in relation to energy balance and macronutrient intake by performing nontargeted global metabolite profiling on plasma collected from 25 male soldiers before and after completing a 4-day, 51-km cross-country ski march that produced high total daily energy expenditures (25...
September 2017: Physiological Reports
https://www.readbyqxmd.com/read/28888048/involvement-of-nutrients-and-nutritional-mediators-in-mitochondrial-3-hydroxy-3-methylglutaryl-coa-synthase-gene-expression
#3
Tania Rescigno, Anna Capasso, Mario Felice Tecce
Mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase (HMGCS2) catalyses the first step of ketogenesis and is critical in various metabolic conditions. Several nutrient molecules were able to differentially modulate HMGCS2 expression levels. Docosahexaenoic acid (DHA, C22:6, n-3), eicosapentaenoic acid (EPA, C20:5, n-3), arachidonic acid (AA, C20:4, n-6) and glucose increased HMGCS2 mRNA and protein levels in HepG2 hepatoma cells, while fructose decreased them. The effect of n-6 AA resulted significantly higher than that of n-3 PUFA, but when combined all these molecules were far less efficient...
September 9, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28865848/grain-challenge-affects-systemic-and-hepatic-molecular-biomarkers-of-inflammation-stress-and-metabolic-responses-to-a-greater-extent-in-holstein-than-jersey-cows
#4
T Xu, F C Cardoso, A Pineda, E Trevisi, X Shen, F Rosa, J S Osorio, J J Loor
Long-term feeding of high-grain diets to dairy cows often results in systemic inflammation characterized by alterations in acute-phase proteins and other biomarkers, both in plasma and immune-responsive tissues like the liver. The molecular and systemic changes that characterize an acute grain feeding challenge remain unclear. The current study involved 6 Holstein and 6 Jersey cows in a replicated 2 × 2 Latin square. Periods (10 d) were divided into 4 stages (S): S1, d 1 to 3, served as baseline with total mixed ration (TMR) ad libitum; S2, d 4, served as restricted feeding, with cows offered 50% of the average daily intake observed in S1; S3, d 5, a grain challenge was performed, in which cows were fed a TMR ad libitum without (CON) or with an additional pellet wheat-barley (1:1; HIG) at 20% of dry matter intake top-dressed onto the TMR; S4, d 6 to 10, served as recovery during which cows were allowed ad libitum access to the TMR...
August 30, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28855921/diagnosis-and-treatment-of-hyperinsulinaemic-hypoglycaemia-and-its-implications-for-paediatric-endocrinology
#5
REVIEW
Huseyin Demirbilek, Sofia A Rahman, Gonul Gulal Buyukyilmaz, Khalid Hussain
Glucose homeostasis requires appropriate and synchronous coordination of metabolic events and hormonal activities to keep plasma glucose concentrations in a narrow range of 3.5-5.5 mmol/L. Insulin, the only glucose lowering hormone secreted from pancreatic β-cells, plays the key role in glucose homeostasis. Insulin release from pancreatic β-cells is mainly regulated by intracellular ATP-generating metabolic pathways. Hyperinsulinaemic hypoglycaemia (HH), the most common cause of severe and persistent hypoglycaemia in neonates and children, is the inappropriate secretion of insulin which occurs despite low plasma glucose levels leading to severe and persistent hypoketotic hypoglycaemia...
2017: International Journal of Pediatric Endocrinology
https://www.readbyqxmd.com/read/28833286/charting-the-transcriptional-regulatory-changes-in-mouse-liver-during-fasting
#6
Elodie Thierion, Duncan T Odom
In a recent paper: Goldstein I, Baek S, Presman DM, Paakinaho V, Swinstead EE, Hager GL. Transcription factor assisted loading and enhancer dynamics dictate the hepatic fasting response. Genome Res. 2017 Mar;27(3):427-39., the authors used a number of functional genomics approaches to explore the transcriptional regulatory dynamics that occur during hepatic fasting. They used chromatin landscape data to identify key fasting-related transcription factors, four of which were further investigated because they are known players of the fasting response: CEBPB (CCAAT enhancer binding-beta), CREB1 (cAMP responsive element binding protein I), GR (glucocorticoid receptor), and PPARA (peroxisome proliferator activated receptor alpha)...
August 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28814987/green-tea-polyphenols-ameliorate-the-early-renal-damage-induced-by-a-high-fat-diet-via-ketogenesis-sirt3-pathway
#7
Weijie Yi, Xiao Xie, Miying Du, Yongjun Bu, Nannan Wu, Hui Yang, Chong Tian, Fangyi Xu, Siyun Xiang, Piwei Zhang, Zhuo Chen, Xuezhi Zuo, Chenjiang Ying
SCOPE: Several reports in the literature have suggested the renoprotective effects of ketone bodies and green tea polyphenols (GTPs). Our previous study found that GTP consumption could elevate the renal expression of the ketogenic rate-limiting enzyme, which was decreased by a high-fat diet (HFD) in rats. Here, we investigated whether ketogenesis can mediate renoprotection by GTPs against an HFD. METHODS AND RESULTS: Wistar rats were fed a standard or HFD with or without GTPs for 18 weeks...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28752050/nrg4-promotes-fuel-oxidation-and-a-healthy-adipokine-profile-to-ameliorate-diet-induced-metabolic-disorders
#8
Zhimin Chen, Guo-Xiao Wang, Sara L Ma, Dae Young Jung, Hyekyung Ha, Tariq Altamimi, Xu-Yun Zhao, Liang Guo, Peng Zhang, Chun-Rui Hu, Ji-Xin Cheng, Gary D Lopaschuk, Jason K Kim, Jiandie D Lin
OBJECTIVE: Brown and white adipose tissue exerts pleiotropic effects on systemic energy metabolism in part by releasing endocrine factors. Neuregulin 4 (Nrg4) was recently identified as a brown fat-enriched secreted factor that ameliorates diet-induced metabolic disorders, including insulin resistance and hepatic steatosis. However, the physiological mechanisms through which Nrg4 regulates energy balance and glucose and lipid metabolism remain incompletely understood. The aims of the current study were: i) to investigate the regulation of adipose Nrg4 expression during obesity and the physiological signals involved, ii) to elucidate the mechanisms underlying Nrg4 regulation of energy balance and glucose and lipid metabolism, and iii) to explore whether Nrg4 regulates adipose tissue secretome gene expression and adipokine secretion...
August 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28723568/loss-of-hepatic-mitochondrial-long-chain-fatty-acid-oxidation-confers-resistance-to-diet-induced-obesity-and-glucose-intolerance
#9
Jieun Lee, Joseph Choi, Ebru S Selen Alpergin, Liang Zhao, Thomas Hartung, Susanna Scafidi, Ryan C Riddle, Michael J Wolfgang
The liver has a large capacity for mitochondrial fatty acid β-oxidation, which is critical for systemic metabolic adaptations such as gluconeogenesis and ketogenesis. To understand the role of hepatic fatty acid oxidation in response to a chronic high-fat diet (HFD), we generated mice with a liver-specific deficiency of mitochondrial long-chain fatty acid β-oxidation (Cpt2(L-/-) mice). Paradoxically, Cpt2(L-/-) mice were resistant to HFD-induced obesity and glucose intolerance with an absence of liver damage, although they exhibited serum dyslipidemia, hepatic oxidative stress, and systemic carnitine deficiency...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28676675/hmgcs2-is-a-key-ketogenic-enzyme-potentially-involved-in-type-1-diabetes-with-high-cardiovascular-risk
#10
Sanket Kumar Shukla, Weijing Liu, Kunal Sikder, Sankar Addya, Amrita Sarkar, Yidong Wei, Khadija Rafiq
Diabetes increases the risk of Cardio-vascular disease (CVD). CVD is more prevalent in type 2 diabetes (T2D) than type 1 diabetes (T1D), but the mortality risk is higher in T1D than in T2D. The pathophysiology of CVD in T1D is poorly defined. To learn more about biological pathways that are potentially involved in T1D with cardiac dysfunction, we sought to identify differentially expressed genes in the T1D heart. Our study used T1D mice with severe hyperglycemia along with significant deficits in echocardiographic measurements...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28555095/nutritional-ketosis-affects-metabolism-and-behavior-in-sprague-dawley-rats-in-both-control-and-chronic-stress-environments
#11
Milene L Brownlow, Seung H Jung, Raquel J Moore, Naomi Bechmann, Ryan Jankord
Nutritional ketosis may enhance cerebral energy metabolism and has received increased interest as a way to improve or preserve performance and resilience. Most studies to date have focused on metabolic or neurological disorders while anecdotal evidence suggests that ketosis may enhance performance in the absence of underlying dysfunction. Moreover, decreased availability of glucose in the brain following stressful events is associated with impaired cognition, suggesting the need for more efficient energy sources...
2017: Frontiers in Molecular Neuroscience
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
#12
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
#13
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
#14
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...
July 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
#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 R 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 an RNAi-based screen targeting the majority of the known metabolic proteins, we recently found that oncogenic BRAF(V600E) up-regulates HMG-CoA lyase (HMGCL), which converts HMG-CoA to acetyl-CoA and a ketone body, acetoacetate, that selectively enhances BRAF(V600E)-dependent MEK1 activation in human cancer...
June 16, 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
#16
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
#17
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
#18
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
#19
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
#20
REVIEW
Caroline E Geisler, Benjamin J Renquist
Fatty liver can be diet, endocrine, drug, virus or genetically 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...
July 2017: Journal of Endocrinology
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