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https://www.readbyqxmd.com/read/29341404/intra-and-inter-subject-variability-for-increases-in-serum-ketone-bodies-in-patients-with-type-2-diabetes-treated-with-the-sodium-glucose-co-transporter-2-inhibitor-canagliflozin
#1
David Polidori, Hiroaki Iijima, Maki Goda, Nobuko Maruyama, Nobuya Inagaki, Peter A Crawford
SGLT2 inhibitors have been associated with increased serum ketone bodies in patients with type 2 diabetes mellitus (T2DM). This analysis evaluated serum ketone body levels and variability in 1,278 Japanese patients with T2DM treated with canagliflozin 100 or 200 mg. Similar mean increases in ketone body concentrations of ~2-fold were seen with both canagliflozin doses. Median (interquartile range) percent change from baseline was 62% (0;180) for acetoacetate and 78% (2;236) for β-hydroxybutyrate. Approximately 2/3 of the variability in each ketone measure was attributed to intra-subject variability...
January 17, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29331071/hepatic-ppar%C3%AE-function-is-controlled-by-polyubiquitination-and-proteasome-mediated-degradation-via-the-coordinated-actions-of-paqr3-and-huwe1
#2
Zilong Zhao, Daqian Xu, Zheng Wang, Lin Wang, Ruomei Han, Zhenzhen Wang, Lujian Liao, Yan Chen
Peroxisome proliferator-activated receptor α (PPARα) is a key transcriptional factor that regulates hepatic lipid catabolism by stimulating fatty acid oxidation and ketogenesis in an adaptive response to nutrient starvation. However, how PPARα is regulated by post-translational modification is poorly understood. Here, we identified that PAQR3 promotes PPARα ubiquitination through the E3 ubiquitin ligase HUWE1, thereby negatively modulating PPARα functions both in vitro and in vivo. Adenovirus-mediated Paqr3 knockdown and liver-specific deletion of the Paqr3 gene reduced hepatic triglyceride levels while increasing fatty acid oxidation and ketogenesis upon fasting...
January 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29280746/congenital-hyperinsulinism-diagnosis-and-treatment-update
#3
Hüseyin Demirbilek, Khalid Hussain
Pancreatic β-cells are finely tuned to secrete insulin so that plasma glucose levels are maintained within a narrow physiological range (3.5-5.5 mmol/L). Hyperinsulinaemic hypoglycaemia (HH) is the inappropriate seretion of insulin in the presence of low plasma glucose levels and leads to severe and persistent hypoglycaemia in neonates and children. Mutations in 12 different key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, HNF1A, HK1, PGM1 and PMM2) that are involved in the regulation of insulin secretion from pancreatic β-cells have been described to be responsible for the underlying molecular mechanisms leading to congenital HH...
December 27, 2017: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/29258446/transcriptome-analysis-of-ruminal-epithelia-revealed-potential-regulatory-mechanisms-involved-in-host-adaptation-to-gradual-high-fermentable-dietary-transition-in-beef-cattle
#4
K Zhao, Y H Chen, G B Penner, M Oba, L L Guan
BACKGROUND: The transition from a high forage to a highly fermentable diet can induce digestive disorders in the rumen. To date, the host mechanisms that regulate the adaption to such dietary transition are largely unknown. To understand the molecular mechanisms involved in such phenomena, RNA-sequencing was performed to identify the changes in the transcriptome of ruminal epithelia during gradual transition from a diet containing 0% to 89% grain. RESULTS: In total, the expression of 11,044, 11,322 and 11,282 genes were detected in ruminal epithelia of beef heifers (n = 15) fed 0%, 72% and 89% barley grain diet, respectively...
December 19, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29241541/adipose-klf15-controls-lipid-handling-to-adapt-to-nutrient-availability
#5
Keiichiro Matoba, Yuan Lu, Rongli Zhang, Eric R Chen, Panjamaporn Sangwung, Benlian Wang, Domenick A Prosdocimo, Mukesh K Jain
Adipose tissue stores energy in the form of triglycerides. The ability to regulate triglyceride synthesis and breakdown based on nutrient status (e.g., fed versus fasted) is critical for physiological homeostasis and dysregulation of this process can contribute to metabolic disease. Whereas much is known about hormonal control of this cycle, transcriptional regulation is not well understood. Here, we show that the transcription factor Kruppel-like factor 15 (KLF15) is critical for the control of adipocyte lipid turnover...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29224880/the-effect-of-different-treatments-for-early-lactation-hyperketonemia-on-liver-triglycerides-glycogen-and-expression-of-key-metabolic-enzymes-in-dairy-cattle
#6
S Mann, F A Leal Yepes, J J Wakshlag, E Behling-Kelly, J A A McArt
Despite the widespread use of treatments for postpartum hyperketonemia in dairy cows, there is currently a lack of evidence comparing their effects on both the resolution of hyperketonemia and the potential effects on the liver of affected animals. The objective of our work was to investigate the effect of commonly used hyperketonemia treatments on hepatic triglyceride and glycogen content as well as on the mRNA and protein abundance of key enzymes involved in gluconeogenesis, ketogenesis, and lipid metabolism...
December 7, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/29222891/effects-of-preoperative-oral-carbohydrate-therapy-on-perioperative-glucose-metabolism-during-oral-maxillofacial-surgery-randomised-clinical-trial
#7
Kanako Esaki, Masanori Tsukamoto, Eiji Sakamoto, Takeshi Yokoyama
BACKGROUND AND OBJECTIVES: Preoperative oral carbohydrate therapy has been suggested to attenuate postoperative insulin resistance. The purpose of this study was to investigate the effect of a carbohydrate-rich beverage given preoperatively on intraoperative glucose metabolism. METHODS AND STUDY DESIGN: This study was a randomised, open-label, placebo-controlled trial. Patients undergoing oral-maxillofacial surgery were divided into two groups. In the glucose group, patients took glucose (50 g/278 mL, p...
2018: Asia Pacific Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/29157602/induction-of-fibroblast-growth-factor-21-does-not-require-activation-of-the-hepatic-x-box-binding-protein-1-in-mice
#8
Shantel Olivares, Anne S Henkel
OBJECTIVE: Fibroblast growth factor 21 (FGF21), a key regulator of the metabolic response to fasting, is highly induced by endoplasmic reticulum (ER) stress. The X-box binding protein 1 (Xbp1) is one of several ER stress proteins that has been shown to directly activate the FGF21 promoter. We aimed to determine whether hepatic Xbp1 is required for induction of hepatic FGF21 in vivo. METHODS: Mice bearing a hepatocyte-specific deletion of Xbp1 (Xbp1(LKO)) were subjected to fasting, pharmacologic ER stress, or a ketogenic diet, all potent stimuli of Fgf21 expression...
December 2017: Molecular Metabolism
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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...
November 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28987936/hmg-coa-synthase-2-drives-brain-metabolic-reprogramming-in-cocaine-exposure
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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