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Cell Metabolism

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https://www.readbyqxmd.com/read/27889388/cellular-aging-contributes-to-failure-of-cold-induced-beige-adipocyte-formation-in-old-mice-and-humans
#1
Daniel C Berry, Yuwei Jiang, Robert W Arpke, Elizabeth L Close, Aki Uchida, David Reading, Eric D Berglund, Michael Kyba, Jonathan M Graff
Cold temperatures induce progenitor cells within white adipose tissue to form beige adipocytes that burn energy and generate heat; this is a potential anti-diabesity therapy. However, the potential to form cold-induced beige adipocytes declines with age. This creates a clinical roadblock to potential therapeutic use in older individuals, who constitute a large percentage of the obesity epidemic. Here we show that aging murine and human beige progenitor cells display a cellular aging, senescence-like phenotype that accounts for their age-dependent failure...
November 21, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27889389/exercise-mimetics-impact-on-health-and-performance
#2
REVIEW
Weiwei Fan, Ronald M Evans
The global epidemic of obesity and its associated chronic diseases is largely attributed to an imbalance between caloric intake and energy expenditure. While physical exercise remains the best solution, the development of muscle-targeted "exercise mimetics" may soon provide a pharmaceutical alternative to battle an increasingly sedentary lifestyle. At the same time, these advances are fueling a raging debate on their escalating use as performance-enhancing drugs in high-profile competitions such as the Olympics...
November 18, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27866838/glutaminolysis-and-fumarate-accumulation-integrate-immunometabolic-and-epigenetic-programs-in-trained-immunity
#3
Rob J W Arts, Boris Novakovic, Rob Ter Horst, Agostinho Carvalho, Siroon Bekkering, Ekta Lachmandas, Fernando Rodrigues, Ricardo Silvestre, Shih-Chin Cheng, Shuang-Yin Wang, Ehsan Habibi, Luís G Gonçalves, Inês Mesquita, Cristina Cunha, Arjan van Laarhoven, Frank L van de Veerdonk, David L Williams, Jos W M van der Meer, Colin Logie, Luke A O'Neill, Charles A Dinarello, Niels P Riksen, Reinout van Crevel, Clary Clish, Richard A Notebaart, Leo A B Joosten, Hendrik G Stunnenberg, Ramnik J Xavier, Mihai G Netea
Induction of trained immunity (innate immune memory) is mediated by activation of immune and metabolic pathways that result in epigenetic rewiring of cellular functional programs. Through network-level integration of transcriptomics and metabolomics data, we identify glycolysis, glutaminolysis, and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by β-glucan in monocytes. Accumulation of fumarate, due to glutamine replenishment of the TCA cycle, integrates immune and metabolic circuits to induce monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases...
November 16, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27866837/high-density-lipoproteins-exert-pro-inflammatory-effects-on-macrophages-via-passive-cholesterol-depletion-and-pkc-nf-%C3%AE%C2%BAb-stat1-irf1-signaling
#4
Emiel P C van der Vorst, Kosta Theodorou, Yongzheng Wu, Marten A Hoeksema, Pieter Goossens, Christina A Bursill, Taghi Aliyev, Leonie F A Huitema, Sander W Tas, Ine M J Wolfs, Marijke J E Kuijpers, Marion J Gijbels, Casper G Schalkwijk, Debby P Y Koonen, Shahla Abdollahi-Roodsaz, Kimberly McDaniels, Chih-Chieh Wang, Michael Leitges, Toby Lawrence, Jogchum Plat, Miranda Van Eck, Kerry-Anne Rye, Lhousseine Touqui, Menno P J de Winther, Erik A L Biessen, Marjo M P C Donners
Membrane cholesterol modulates a variety of cell signaling pathways and functions. While cholesterol depletion by high-density lipoproteins (HDLs) has potent anti-inflammatory effects in various cell types, its effects on inflammatory responses in macrophages remain elusive. Here we show overt pro-inflammatory effects of HDL-mediated passive cholesterol depletion and lipid raft disruption in murine and human primary macrophages in vitro. These pro-inflammatory effects were confirmed in vivo in peritoneal macrophages from apoA-I transgenic mice, which have elevated HDL levels...
November 16, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27889387/diet-microbiome-interactions-in-health-are-controlled-by-intestinal-nitrogen-source-constraints
#5
Andrew J Holmes, Yi Vee Chew, Feyza Colakoglu, John B Cliff, Eline Klaassens, Mark N Read, Samantha M Solon-Biet, Aisling C McMahon, Victoria C Cogger, Kari Ruohonen, David Raubenheimer, David G Le Couteur, Stephen J Simpson
Diet influences health and patterns of disease in populations. How different diets do this and why outcomes of diets vary between individuals are complex and involve interaction with the gut microbiome. A major challenge for predicting health outcomes of the host-microbiome dynamic is reconciling the effects of different aspects of diet (food composition or intake rate) on the system. Here we show that microbial community assembly is fundamentally shaped by a dichotomy in bacterial strategies to access nitrogen in the gut environment...
November 15, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27866836/physiological-suppression-of-lipotoxic-liver-damage%C3%A2-by-complementary-actions-of-hdac3-and%C3%A2-scap-srebp
#6
Romeo Papazyan, Zheng Sun, Yong Hoon Kim, Paul M Titchenell, David A Hill, Wenyun Lu, Manashree Damle, Min Wan, Yuxiang Zhang, Erika R Briggs, Joshua D Rabinowitz, Mitchell A Lazar
Liver fat accumulation precedes non-alcoholic steatohepatitis, an increasing cause of end-stage liver disease. Histone deacetylase 3 (HDAC3) is required for hepatic triglyceride homeostasis, and sterol regulatory element binding protein (SREBP) regulates the lipogenic response to feeding, but the crosstalk between these pathways is unknown. Here we show that inactivation of SREBP by hepatic deletion of SREBP cleavage activating protein (SCAP) abrogates the increase in lipogenesis caused by loss of HDAC3, but fatty acid oxidation remains defective...
November 10, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27839907/immunotherapy-for-type-1-diabetes-why-do-current-protocols-not-halt-the-underlying-disease-process
#7
Hubert Kolb, Matthias von Herrath
T cell-directed immunosuppression only transiently delays the loss of β cell function in recent-onset type 1 diabetes. We argue here that the underlying disease process is carried by innate immune reactivity. Inducing a non-polarized functional state of local innate immunity will support regulatory T cell development and β cell proliferation.
November 5, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27839908/cellular-sites-and-mechanisms-linking-reduction-of-dipeptidyl-peptidase-4-activity-to-control-of-incretin-hormone-action-and-glucose-homeostasis
#8
Erin E Mulvihill, Elodie M Varin, Bojana Gladanac, Jonathan E Campbell, John R Ussher, Laurie L Baggio, Bernardo Yusta, Jennifer Ayala, Melissa A Burmeister, Dianne Matthews, K W Annie Bang, Julio E Ayala, Daniel J Drucker
Pharmacological inhibition of the dipeptidyl peptidase-4 (DPP4) enzyme potentiates incretin action and is widely used to treat type 2 diabetes. Nevertheless, the precise cells and tissues critical for incretin degradation and glucose homeostasis remain unknown. Here, we use mouse genetics and pharmacologic DPP4 inhibition to identify DPP4(+) cell types essential for incretin action. Although enterocyte DPP4 accounted for substantial intestinal DPP4 activity, ablation of enterocyte DPP4 in Dpp4(Gut-/-) mice did not produce alterations in plasma DPP4 activity, incretin hormone levels, and glucose tolerance...
November 4, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27818259/transintestinal-cholesterol-transport-is-active-in-mice-and-humans-and-controls-ezetimibe-induced-fecal-neutral-sterol-excretion
#9
Lily Jakulj, Theo H van Dijk, Jan Freark de Boer, Ruud S Kootte, Marleen Schonewille, Yared Paalvast, Theo Boer, Vincent W Bloks, Renze Boverhof, Max Nieuwdorp, Ulrich H W Beuers, Erik S G Stroes, Albert K Groen
Except for conversion to bile salts, there is no major cholesterol degradation pathway in mammals. Efficient excretion from the body is therefore a crucial element in cholesterol homeostasis. Yet, the existence and importance of cholesterol degradation pathways in humans is a matter of debate. We quantified cholesterol fluxes in 15 male volunteers using a cholesterol balance approach. Ten participants repeated the protocol after 4 weeks of treatment with ezetimibe, an inhibitor of intestinal and biliary cholesterol absorption...
November 2, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27818260/nuclear-proteomics-uncovers-diurnal-regulatory-landscapes-in-mouse-liver
#10
Jingkui Wang, Daniel Mauvoisin, Eva Martin, Florian Atger, Antonio Núñes Galindo, Loïc Dayon, Federico Sizzano, Alessio Palini, Martin Kussmann, Patrice Waridel, Manfredo Quadroni, Vjekoslav Dulić, Felix Naef, Frédéric Gachon
Diurnal oscillations of gene expression controlled by the circadian clock and its connected feeding rhythm enable organisms to coordinate their physiologies with daily environmental cycles. While available techniques yielded crucial insights into regulation at the transcriptional level, much less is known about temporally controlled functions within the nucleus and their regulation at the protein level. Here, we quantified the temporal nuclear accumulation of proteins and phosphoproteins from mouse liver by SILAC proteomics...
October 31, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27818261/phosphorylation-is-a-central-mechanism-for-circadian-control-of-metabolism-and-physiology
#11
Maria S Robles, Sean J Humphrey, Matthias Mann
Circadian clocks are self-sustainable endogenous oscillators, present in virtually every cell, driving daily cycles of metabolism and physiology. The molecular mechanism of the circadian clock is based on interconnected transcriptional and translational feedback loops. While many studies have addressed circadian rhythms of the transcriptome and, to a lesser extent, the proteome, none have investigated the phosphoproteome. We apply mass spectrometry-based phosphoproteomics to obtain the first global in vivo quantification of circadian phosphorylation in mammals...
October 29, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27818258/adipocyte-ceramides-regulate-subcutaneous-adipose-browning-inflammation-and-metabolism
#12
Bhagirath Chaurasia, Vincent Andre Kaddai, Graeme Iain Lancaster, Darren C Henstridge, Sandhya Sriram, Dwight Lark Anolin Galam, Venkatesh Gopalan, K N Bhanu Prakash, S Sendhil Velan, Sarada Bulchand, Teh Jing Tsong, Mei Wang, Monowarul Mobin Siddique, Guan Yuguang, Kristmundur Sigmundsson, Natalie A Mellet, Jacquelyn M Weir, Peter J Meikle, M Shabeer Bin M Yassin, Asim Shabbir, James A Shayman, Yoshio Hirabayashi, Sue-Anne Toh Ee Shiow, Shigeki Sugii, Scott A Summers
Adipocytes package incoming fatty acids into triglycerides and other glycerolipids, with only a fraction spilling into a parallel biosynthetic pathway that produces sphingolipids. Herein, we demonstrate that subcutaneous adipose tissue of type 2 diabetics contains considerably more sphingolipids than non-diabetic, BMI-matched counterparts. Whole-body and adipose tissue-specific inhibition/deletion of serine palmitoyltransferase (Sptlc), the first enzyme in the sphingolipid biosynthesis cascade, in mice markedly altered adipose morphology and metabolism, particularly in subcutaneous adipose tissue...
October 21, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27773696/circadian-clock-interaction-with-hif1%C3%AE-mediates-oxygenic-metabolism-and-anaerobic-glycolysis-in-skeletal-muscle
#13
Clara Bien Peek, Daniel C Levine, Jonathan Cedernaes, Akihiko Taguchi, Yumiko Kobayashi, Stacy J Tsai, Nicolle A Bonar, Maureen R McNulty, Kathryn Moynihan Ramsey, Joseph Bass
Circadian clocks are encoded by a transcription-translation feedback loop that aligns energetic processes with the solar cycle. We show that genetic disruption of the clock activator BMAL1 in skeletal myotubes and fibroblasts increased levels of the hypoxia-inducible factor 1α (HIF1α) under hypoxic conditions. Bmal1(-/-) myotubes displayed reduced anaerobic glycolysis, mitochondrial respiration with glycolytic fuel, and transcription of HIF1α targets Phd3, Vegfa, Mct4, Pk-m, and Ldha, whereas abrogation of the clock repressors CRY1/2 stabilized HIF1α in response to hypoxia...
October 19, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27773695/rhythmic-oxygen-levels-reset-circadian-clocks-through-hif1%C3%AE
#14
Yaarit Adamovich, Benjamin Ladeuix, Marina Golik, Maarten P Koeners, Gad Asher
The mammalian circadian system consists of a master clock in the brain that synchronizes subsidiary oscillators in peripheral tissues. The master clock maintains phase coherence in peripheral cells through systemic cues such as feeding-fasting and temperature cycles. Here, we examined the role of oxygen as a resetting cue for circadian clocks. We continuously measured oxygen levels in living animals and detected daily rhythms in tissue oxygenation. Oxygen cycles, within the physiological range, were sufficient to synchronize cellular clocks in a HIF1α-dependent manner...
October 19, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27773697/reciprocal-regulation-between-the-circadian-clock-and-hypoxia-signaling-at-the-genome-level-in-mammals
#15
Yaling Wu, Dingbin Tang, Na Liu, Wei Xiong, Huanwei Huang, Yang Li, Zhixiong Ma, Haijiao Zhao, Peihao Chen, Xiangbing Qi, Eric Erquan Zhang
Circadian regulation is critically important in maintaining metabolic and physiological homeostasis. However, little is known about the possible influence of the clock on physiological abnormalities occurring under pathological conditions. Here, we report the discovery that hypoxia, a condition that causes catastrophic bodily damage, is gated by the circadian clock in vivo. Hypoxia signals conversely regulate the clock by slowing the circadian cycle and dampening the amplitude of oscillations in a dose-dependent manner...
October 14, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27746051/metformin-targets-central-carbon-metabolism-and-reveals-mitochondrial-requirements-in-human-cancers
#16
Xiaojing Liu, Iris L Romero, Lacey M Litchfield, Ernst Lengyel, Jason W Locasale
Repurposing metformin for cancer therapy is attractive due to its safety profile, epidemiological evidence, and encouraging data from human clinical trials. Although it is known to systemically affect glucose metabolism in liver, muscle, gut, and other tissues, the molecular determinants that predict a patient response in cancer remain unknown. Here, we carry out an integrative metabolomics analysis of metformin action in ovarian cancer. Metformin accumulated in patient biopsies, and pathways involving nucleotide metabolism, redox, and energy status, all related to mitochondrial metabolism, were affected in treated tumors...
October 12, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27720676/the-assembly-pathway-of-mitochondrial-respiratory-chain-complex-i
#17
Sergio Guerrero-Castillo, Fabian Baertling, Daniel Kownatzki, Hans J Wessels, Susanne Arnold, Ulrich Brandt, Leo Nijtmans
Mitochondrial complex I is the largest integral membrane enzyme of the respiratory chain and consists of 44 different subunits encoded in the mitochondrial and nuclear genome. Its biosynthesis is a highly complicated and multifaceted process involving at least 14 additional assembly factors. How these subunits assemble into a functional complex I and where the assembly factors come into play is largely unknown. Here, we applied a dynamic complexome profiling approach to elucidate the assembly of human mitochondrial complex I and its further incorporation into respiratory chain supercomplexes...
September 30, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27693378/tissue-immunometabolism-development-physiology-and-pathobiology
#18
Kevin Man, Vassily I Kutyavin, Ajay Chawla
Evolution of metazoans resulted in the specialization of cellular and tissue function. This was accomplished by division of labor, which allowed tissue parenchymal cells to prioritize their core functions while ancillary functions were delegated to tissue accessory cells, such as immune, stromal, and endothelial cells. In metabolic organs, the accessory cells communicate with their clients, the tissue parenchymal cells, to optimize cellular processes, allowing organisms to adapt to changes in their environment...
September 21, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27667664/a-genome-wide-crispr-death-screen-identifies-genes-essential-for-oxidative-phosphorylation
#19
Jason D Arroyo, Alexis A Jourdain, Sarah E Calvo, Carmine A Ballarano, John G Doench, David E Root, Vamsi K Mootha
Oxidative phosphorylation (OXPHOS) is the major pathway for ATP production in humans. Deficiencies in OXPHOS can arise from mutations in either mitochondrial or nuclear genomes and comprise the largest collection of inborn errors of metabolism. At present we lack a complete catalog of human genes and pathways essential for OXPHOS. Here we introduce a genome-wide CRISPR "death screen" that actively selects dying cells to reveal human genes required for OXPHOS, inspired by the classic observation that human cells deficient in OXPHOS survive in glucose but die in galactose...
September 9, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27641100/one-carbon-metabolism-in-health-and-disease
#20
Gregory S Ducker, Joshua D Rabinowitz
One-carbon (1C) metabolism, mediated by the folate cofactor, supports multiple physiological processes. These include biosynthesis (purines and thymidine), amino acid homeostasis (glycine, serine, and methionine), epigenetic maintenance, and redox defense. Both within eukaryotic cells and across organs, 1C metabolic reactions are compartmentalized. Here we review the fundamentals of mammalian 1C metabolism, including the pathways active in different compartments, cell types, and biological states. Emphasis is given to recent discoveries enabled by modern genetics, analytical chemistry, and isotope tracing...
September 8, 2016: Cell Metabolism
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