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Ketogenesis

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https://www.readbyqxmd.com/read/29107291/absence-of-the-kinase-s6k1-mimics-the-effect-of-chronic-endurance-exercise-on-glucose-tolerance-and-muscle-oxidative-stress
#1
C Binsch, T Jelenik, A Pfitzer, M Dille, S Müller-Lühlhoff, S Hartwig, S Karpinski, S Lehr, D G Kabra, A Chadt, M Roden, H Al-Hasani, T R Castañeda
OBJECTIVE: Ribosomal protein S6 Kinase-1 (S6K1) has been linked to resistance exercise-mediated improvements in glycemia. We hypothesized that S6K1 may also play a role in regulating glycemic control in response to endurance exercise training. METHODS: S6k1-knockout (S6K1KO) and WT mice on a 60 cal% high-fat diet were trained for 4 weeks on treadmills, metabolically phenotyped, and compared to sedentary controls. RESULTS: WT mice showed improved glucose tolerance after training...
November 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29078811/dengue-hemorrhagic-fever-complicated-with-transient-diabetic-ketoacidosis-a-case-report
#2
Chamara Dalugama, Indika Bandara Gawarammana
BACKGROUND: The increasing global prevalence of both dengue and diabetes may warrant closer observation for glycemic control and adapted fluid management to diminish the risk for a severe clinical presentation of dengue. Dengue illness is rarely known to precipitate diabetic ketoacidosis among diabetic patients. Both type 1 and type 2 diabetes increase the release of pro-inflammatory cytokines by various mechanisms and increase the risk of plasma leak in dengue fever. Acute pancreatitis is an atypical and rare presentation of dengue fever...
October 28, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29068709/altered-patterns-of-early-metabolic-decompensation-in-type-1-diabetes-during-treatment-with-a-sglt2-inhibitor-an-insulin-pump-suspension-study
#3
Neha S Patel, Michelle A Van Name, Eda Cengiz, Lori R Carria, Stuart A Weinzimer, William V Tamborlane, Jennifer L Sherr
BACKGROUND: Enthusiasm for the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as an adjunctive treatment in type 1 diabetes (T1D) has been offset by the possible increased risk of diabetic ketoacidosis (DKA). Since pump-treated T1D patients are susceptible to DKA due to infusion site problems, this study was undertaken to assess how treatment with SGLT2i affects patterns of early metabolic decompensation following suspension of basal insulin. METHODS: Ten T1D participants (age 19-35 years, duration 10 ± 8 years, A1c 7...
November 2017: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/29068248/diabetic-ketoacidosis-in-the-cat-recognition-and-essential-treatment
#4
Elke Rudloff
Practical relevance: Diabetic ketoacidosis (DKA) is a not uncommon emergency in both newly diagnosed and poorly regulated diabetic cats. When there is a heightened metabolic rate and energy requirement due to concurrent illness, an increase in the release of glucose counter-regulatory hormones causes insulin receptor resistance, lipolysis, free fatty acid release and ketogenesis. This necessitates not only treatment to eliminate the ketosis and control blood glucose, but also investigation of concurrent illnesses...
November 2017: Journal of Feline Medicine and Surgery
https://www.readbyqxmd.com/read/29030856/mitochondrial-3-hydroxy-3-methylglutaryl-coa-synthase-deficiency-unique-presenting-laboratory-values-and-a-review-of-biochemical-and-clinical-features
#5
Erin Conboy, Filippo Vairo, Matthew Schultz, Katherine Agre, Ross Ridsdale, David Deyle, Devin Oglesbee, Dimitar Gavrilov, Eric W Klee, Brendan Lanpher
We report an 8-month-old infant with decreased consciousness after a febrile episode and reduced oral intake. He was profoundly acidotic but his lactate was normal. Serum triglycerides were markedly elevated and HDL cholesterol was very low. The urine organic acid analysis during the acute episode revealed a complex pattern of relative hypoketotic dicarboxylic aciduria, suggestive of a potential fatty acid oxidation disorder. MRI showed extensive brain abnormalities concerning for a primary energy deficiency...
October 14, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28990936/olfactory-receptor-544-reduces-adiposity-by-steering-fuel-preference-toward-fats
#6
Chunyan Wu, Su Hyeon Hwang, Yaoyao Jia, Joobong Choi, Yeon-Ji Kim, Dahee Choi, Duleepa Pathiraja, In-Geol Choi, Seung-Hoi Koo, Sung-Joon Lee
Olfactory receptors (ORs) are present in tissues outside the olfactory system; however, the function of these receptors remains relatively unknown. Here, we determined that olfactory receptor 544 (Olfr544) is highly expressed in the liver and adipose tissue of mice and regulates cellular energy metabolism and obesity. Azelaic acid (AzA), an Olfr544 ligand, specifically induced PKA-dependent lipolysis in adipocytes and promoted fatty acid oxidation (FAO) and ketogenesis in liver, thus shifting the fuel preference to fats...
October 9, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28987936/hmg-coa-synthase-2-drives-brain-metabolic-reprogramming-in-cocaine-exposure
#7
Xue Shao, Yunxuan Tang, Hailei Long, Hui Gu, Jie Zhang, Pengchi Deng, Yinglan Zhao, Xiaobo Cen
The brain is a high energy-consuming organ that typically utilizes glucose as the main energy source for cerebral activity. When glucose becomes scarce under conditions of stress, ketone bodies, such as β-hydroxybutyrate, acetoacetate and acetone, become extremely important. Alterations in brain energy metabolism have been observed in psychostimulant abusers; however, the mode of brain metabolic programming in cocaine dependence remains largely unknown. Here, we profiled the metabolites and metabolic enzymes from brain nucleus accumbens (NAc) of mice exposed to cocaine...
October 4, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28941596/robust-suppression-of-cardiac-energy-catabolism-with-marked-accumulation-of-energy-substrates-during-lipopolysaccharide-induced-cardiac-dysfunction-in-mice
#8
Yogi Umbarawan, Mas Rizky A A Syamsunarno, Hideru Obinata, Aiko Yamaguchi, Hiroaki Sunaga, Hiroki Matsui, Takako Hishiki, Tomomi Matsuura, Norimichi Koitabashi, Masaru Obokata, Hirofumi Hanaoka, Anwarul Haque, Fumio Kunimoto, Yoshito Tsushima, Makoto Suematsu, Masahiko Kurabayashi, Tatsuya Iso
BACKGROUND: Myocardial contractile dysfunction in sepsis has been attributed mainly to increased inflammatory cytokines, insulin resistance, and impaired oxidative phosphorylation of fatty acids (FAs). However, precise molecular mechanisms underlying the cardiac dysfunction in sepsis remain to be determined. We previously reported major shift in myocardial energy substrates from FAs to glucose, and increased hepatic ketogenesis in mice lacking fatty acid-binding protein 4 (FABP4) and FABP5 (DKO)...
September 20, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28931870/inactivation-of-hmgcl-promotes-proliferation-and-metastasis-of-nasopharyngeal-carcinoma-by-suppressing-oxidative-stress
#9
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
#10
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
#11
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
#12
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...
November 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28855921/diagnosis-and-treatment-of-hyperinsulinaemic-hypoglycaemia-and-its-implications-for-paediatric-endocrinology
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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