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Ketogenesis

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https://www.readbyqxmd.com/read/28304146/liraglutide-acutely-suppresses-glucagon-lipolysis-and-ketogenesis-in-type-1-diabetes
#1
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
#2
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...
March 17, 2017: Endocrine
https://www.readbyqxmd.com/read/28302729/phagocytosis-dependent-ketogenesis-in-retinal-pigment-epithelium
#3
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 (FAO) 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-hydroxy-butyrate (β-HB) in the apical media following ingestion of OS by human fetal RPE and ARPE19 cells cultured on transwell inserts...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28249286/impact-of-fibroblast-growth-factors-19-and-21-in-bariatric-metabolism
#4
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
https://www.readbyqxmd.com/read/28242634/ketone-body-infusion-with-3-hydroxybutyrate-reduces-myocardial-glucose-uptake-and-increases-blood-flow-in-humans-a-positron-emission-tomography-study
#5
Lars C Gormsen, Mads Svart, Henrik Holm Thomsen, Esben Søndergaard, Mikkel H Vendelbo, Nana Christensen, Lars Poulsen Tolbod, Hendrik Johannes Harms, Roni Nielsen, Henrik Wiggers, Niels Jessen, Jakob Hansen, Hans Erik Bøtker, Niels Møller
BACKGROUND: High levels of ketone bodies are associated with improved survival as observed with regular exercise, caloric restriction, and-most recently-treatment with sodium-glucose linked transporter 2 inhibitor antidiabetic drugs. In heart failure, indices of ketone body metabolism are upregulated, which may improve energy efficiency and increase blood flow in skeletal muscle and the kidneys. Nevertheless, it is uncertain how ketone bodies affect myocardial glucose uptake and blood flow in humans...
February 27, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28222147/the-desert-gerbil-psammomys-obesus-as-a-model-for-metformin-sensitive-nutritional-type-2-diabetes-to-protect-hepatocellular-metabolic-damage-impact-of-mitochondrial-redox-state
#6
Inès Gouaref, Dominique Detaille, Nicolas Wiernsperger, Naim Akhtar Khan, Xavier Leverve, Elhadj-Ahmed Koceir
INTRODUCTION: While metformin (MET) is the most widely prescribed antidiabetic drug worldwide, its beneficial effects in Psammomys obesus (P. obesus), a rodent model that mimics most of the metabolic features of human diabetes, have not been explored thoroughly. Here, we sought to investigate whether MET might improve insulin sensitivity, glucose homeostasis, lipid profile as well as cellular redox and energy balance in P. obesus maintained on a high energy diet (HED). MATERIALS AND METHODS: P...
2017: PloS One
https://www.readbyqxmd.com/read/28215897/effects-of-body-condition-monensin-and-essential-oils-on-ruminal-lipopolysaccharide-concentration-inflammatory-markers-and-endoplasmatic-reticulum-stress-of-transition-dairy-cows
#7
C Drong, S Bühler, J Frahm, L Hüther, U Meyer, D von Soosten, D K Gessner, K Eder, H Sauerwein, S Dänicke
Evidence exists that dairy cows experience inflammatory-like phenomena in the transition period. Rumen health and alterations in metabolic processes and gene networks in the liver as the central metabolic organ might be key factors for cows' health and productivity in early lactation. This study made use of an animal model to generate experimental groups with different manifestations of postpartal fat mobilization and ketogenesis. In total, 60 German Holstein cows were allocated 6 wk antepartum to 3 high-body condition score (BCS) groups (BCS 3...
February 16, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28193308/review-exogenous-butyrate-implications-for-the-functional-development-of-ruminal-epithelium-and-calf-performance
#8
B Niwińska, E Hanczakowska, M B Arciszewski, R Klebaniuk
The importance of the use of exogenous butyrate in calves' diets is due to its role as a factor stimulating the functional development of ruminal epithelium and improving calf performance during the transition from preruminant to ruminant status. Our review will first present results related to effects of the administration of butyrate in calves' diets on the development of ruminal epithelium toward a more effective absorption and metabolism of fermentation products from the rumen. The introduction of sodium butyrate at a level of about 0...
February 14, 2017: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/28183452/controversies-in-the-management-of-hyperglycaemic-emergencies-in-adults-with-diabetes
#9
REVIEW
Luís Cardoso, Nuno Vicente, Dírcea Rodrigues, Leonor Gomes, Francisco Carrilho
Hyperglycaemic emergencies are associated with significant morbi-mortality and healthcare costs. Management consists on fluid replacement, insulin therapy, and electrolyte correction. However, some areas of patient management remain debatable. In patients without respiratory failure or haemodynamic instability, arterial and venous pH and bicarbonate measurements are comparable. Fluid choice varies upon replenishment phase and patient's condition. If patient is severely hypovolaemic, normal saline solution should be the first option...
March 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28112679/mechanism-for-leptin-s-acute-insulin-independent-effect-to-reverse-diabetic-ketoacidosis
#10
Rachel J Perry, Liang Peng, Abudukadier Abulizi, Lynn Kennedy, Gary W Cline, Gerald I Shulman
The mechanism by which leptin reverses diabetic ketoacidosis (DKA) is unknown. We examined the acute insulin-independent effects of leptin replacement therapy in a streptozotocin-induced rat model of DKA. Leptin infusion reduced rates of lipolysis, hepatic glucose production (HGP), and hepatic ketogenesis by 50% within 6 hours and were independent of any changes in plasma glucagon concentrations; these effects were abrogated by coinfusion of corticosterone. Treating leptin- and corticosterone-infused rats with an adipose triglyceride lipase inhibitor blocked corticosterone-induced increases in plasma glucose concentrations and rates of HGP and ketogenesis...
February 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28089569/prevention-of-dietary-fat-fueled-ketogenesis-attenuates-braf-v600e-tumor-growth
#11
Siyuan Xia, Ruiting Lin, Lingtao Jin, Liang Zhao, Hee-Bum Kang, Yaozhu Pan, Shuangping Liu, Guoqing Qian, Zhiyu Qian, Evmorfia Konstantakou, Baotong Zhang, Jin-Tang Dong, Young Rock Chung, Omar Abdel-Wahab, Taha Merghoub, Lu Zhou, Ragini R Kudchadkar, David H Lawson, Hanna J Khoury, Fadlo R Khuri, Lawrence H Boise, Sagar Lonial, Benjamin H Lee, Brian P Pollack, Jack L Arbiser, Jun Fan, Qun-Ying Lei, Jing Chen
Lifestyle factors, including diet, play an important role in the survival of cancer patients. However, the molecular mechanisms underlying pathogenic links between diet and particular oncogenic mutations in human cancers remain unclear. We recently reported that the ketone body acetoacetate selectively enhances BRAF V600E mutant-dependent MEK1 activation in human cancers. Here we show that a high-fat ketogenic diet increased serum levels of acetoacetate, leading to enhanced tumor growth potential of BRAF V600E-expressing human melanoma cells in xenograft mice...
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28004777/gene-expression-differences-in-longissimus-muscle-of-nelore-steers-genetically-divergent-for-residual-feed-intake
#12
Polyana C Tizioto, Luiz L Coutinho, Priscila S N Oliveira, Aline S M Cesar, Wellison J S Diniz, Andressa O Lima, Marina I Rocha, Jared E Decker, Robert D Schnabel, Gerson B Mourão, Rymer R Tullio, Adhemar Zerlotini, Jeremy F Taylor, Luciana C A Regitano
Residual feed intake (RFI), a measure of feed efficiency (FE), is defined as the difference between the observed and the predictable feed intake considering size and growth of the animal. It is extremely important to beef production systems due to its impact on the allocation of land areas to alternative agricultural production, animal methane emissions, food demand and cost of production. Global differential gene expression analysis between high and low RFI groups (HRFI and LRFI: less and more efficient, respectively) revealed 73 differentially expressed (DE) annotated genes in Longissimus thoracis (LT) muscle of Nelore steers...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27995076/diagnosis-of-lchad-tfp-deficiency-in-an-at-risk-newborn-using-umbilical-cord-blood-acylcarnitine-analysis
#13
Donna B Raval, Kristina P Cusmano-Ozog, Omar Ayyub, Callie Jenevein, Laura H Kofman, Brendan Lanpher, Natalie Hauser, Debra S Regier
Trifunctional protein deficiency/Long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHAD/TFP) deficiency is a disorder of fatty acid oxidation and ketogenesis. Severe neonatal lactic acidosis, cardiomyopathy, and hepatic dysfunction are caused by the accumulation of toxic long-chain acylcarnitines. The feasibility of umbilical cord blood use in screening for acylcarnitine analysis and free carnitine has been hypothesized but not reported in LCHAD/TFP neonates. We present a 4 week old female who was at risk of inheriting LCHAD/TFP deficiency and was diagnosed at the time of delivery using umbilical cord blood...
March 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/27983603/regulation-of-ketone-body-metabolism-and-the-role-of-ppar%C3%AE
#14
REVIEW
Maja Grabacka, Malgorzata Pierzchalska, Matthew Dean, Krzysztof Reiss
Ketogenesis and ketolysis are central metabolic processes activated during the response to fasting. Ketogenesis is regulated in multiple stages, and a nuclear receptor peroxisome proliferator activated receptor α (PPARα) is one of the key transcription factors taking part in this regulation. PPARα is an important element in the metabolic network, where it participates in signaling driven by the main nutrient sensors, such as AMP-activated protein kinase (AMPK), PPARγ coactivator 1α (PGC-1α), and mammalian (mechanistic) target of rapamycin (mTOR) and induces hormonal mediators, such as fibroblast growth factor 21 (FGF21)...
December 13, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27982131/creb3l3-controls-fatty-acid-oxidation-and-ketogenesis-in-synergy-with-ppar%C3%AE
#15
Yoshimi Nakagawa, Aoi Satoh, Hitomi Tezuka, Song-Iee Han, Kenta Takei, Hitoshi Iwasaki, Shigeru Yatoh, Naoya Yahagi, Hiroaki Suzuki, Yasumasa Iwasaki, Hirohito Sone, Takashi Matsuzaka, Nobuhiro Yamada, Hitoshi Shimano
CREB3L3 is involved in fatty acid oxidation and ketogenesis in a mutual manner with PPARα. To evaluate relative contribution, a combination of knockout and transgenic mice was investigated. On a ketogenic-diet (KD) that highlights capability of hepatic ketogenesis, Creb3l3(-/-) mice exhibited reduction of expression of genes for fatty oxidation and ketogenesis comparable to Ppara(-/-) mice. Most of the genes were further suppressed in double knockout mice indicating independent contribution of hepatic CREB3L3...
December 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27966366/metabolic-phenotype-of-obesity-in-a-saudi-population
#16
Muhammad Saeed Ahmad, Munirah Alsaleh, Torben Kimhofer, Sultan Ahmad, Wisam Jamal, Siraj Omar Wali, Jeremy Kirk Nicholson, Zoheir Abdullah Damanhouri, Elaine Holmes
Metabolic phenotyping of obese populations can shed light on understanding environmental interactions underpinning obesogenesis. Obesity and its comorbidities are a major health and socioeconomic concern globally and are highly prevalent in the Middle East. We employed nuclear magnetic resonance spectroscopy to characterize the metabolic signature of urine and blood plasma for a cohort of obese (n = 50) compared to non-obese (n = 48) Saudi participants. The urinary metabolic phenotype of obesity was characterized by higher concentrations of N-acetyl glycoprotein fragments, bile acids, lysine, and methylamines and lower concentrations of tricarboxylic acid cycle intermediates, glycine, and gut microbial metabolites...
January 20, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/27935584/ketogenesis-contributes-to-intestinal-cell-differentiation
#17
Qingding Wang, Yuning Zhou, Piotr Rychahou, Teresa W-M Fan, Andrew N Lane, Heidi L Weiss, B Mark Evers
The intestinal epithelium undergoes a continual process of proliferation, differentiation and apoptosis. Previously, we have shown that the PI3K/Akt/mTOR pathway has a critical role in intestinal homeostasis. However, the downstream targets mediating the effects of mTOR in intestinal cells are not known. Here, we show that the ketone body β-hydroxybutyrate (βHB), an endogenous inhibitor of histone deacetylases (HDACs) induces intestinal cell differentiation as noted by the increased expression of differentiation markers (Mucin2 (MUC2), lysozyme, IAP, sucrase-isomaltase, KRT20, villin, Caudal-related homeobox transcription factor 2 (CDX2) and p21(Waf1))...
March 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27930814/septic-ketoacidosis-a-potentially-lethal-entity-with-renal-tubular-epithelial-vacuolization
#18
Chong Zhou, Roger W Byard
Fatal ketoacidosis due to diabetes mellitus, alcoholism, and starvation may produce characteristic basal vacuolization of renal tubular epithelial cells (RTEC). Septic ketoacidosis has recently been recognized clinically as a distinct condition in which septicemia can lead to elevation of ketones and various anions unrelated to diabetes mellitus, alcoholism, or caloric deprivation. We report four lethal cases with significantly elevated vitreous ketones secondary to sepsis and/or severe localized infection in individuals with no history of diabetes mellitus, alcoholism, or starvation...
January 2017: Journal of Forensic Sciences
https://www.readbyqxmd.com/read/27903579/medium-chain-acyl-coenzyme-a-dehydrogenase-deficiency-mcadd-a-cause-of-severe-hypoglycaemia-in-an-apparently-well-child
#19
Kene Ebuka Maduemem
Medium-chain acyl-Coenzyme A dehydrogenase deficiency (MCADD) is a disorder of fatty acid β oxidation inherited in an autosomal recessive manner. The enzyme is useful in hepatic ketogenesis, a major source of energy once hepatic glycogen stores become depleted during prolonged fasting. It is a cause of hypoketotic hypoglycaemia in a previously well child. MCADD is not part of newborn screening in Ireland; children are likely to be missed if routine hypoglycaemic screen is not instituted when blood glucose level is below 2...
November 30, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27897405/premorbid-obesity-but-not-nutrition-prevents-critical-illness-induced-muscle-wasting-and-weakness
#20
Chloë Goossens, Mirna Bastos Marques, Sarah Derde, Sarah Vander Perre, Thomas Dufour, Steven E Thiessen, Fabian Güiza, Thomas Janssens, Greet Hermans, Ilse Vanhorebeek, Katrien De Bock, Greet Van den Berghe, Lies Langouche
BACKGROUND: The 'obesity paradox' of critical illness refers to better survival with a higher body mass index. We hypothesized that fat mobilized from excess adipose tissue during critical illness provides energy more efficiently than exogenous macronutrients and could prevent lean tissue wasting. METHODS: In lean and premorbidly obese mice, the effect of 5 days of sepsis-induced critical illness on body weight and composition, muscle wasting, and weakness was assessed, each with fasting and parenteral feeding...
February 2017: Journal of Cachexia, Sarcopenia and Muscle
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