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Cell Metabolism

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https://www.readbyqxmd.com/read/28988825/pgc-1%C3%AE-promotes-breast-cancer-metastasis-and-confers-bioenergetic-flexibility-against-metabolic-drugs
#1
Sylvia Andrzejewski, Eva Klimcakova, Radia M Johnson, Sébastien Tabariès, Matthew G Annis, Shawn McGuirk, Jason J Northey, Valérie Chénard, Urshila Sriram, David J Papadopoli, Peter M Siegel, Julie St-Pierre
Metabolic adaptations play a key role in fueling tumor growth. However, less is known regarding the metabolic changes that promote cancer progression to metastatic disease. Herein, we reveal that breast cancer cells that preferentially metastasize to the lung or bone display relatively high expression of PGC-1α compared with those that metastasize to the liver. PGC-1α promotes breast cancer cell migration and invasion in vitro and augments lung metastasis in vivo. Pro-metastatic capabilities of PGC-1α are linked to enhanced global bioenergetic capacity, facilitating the ability to cope with bioenergetic disruptors like biguanides...
October 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28988824/citrobacter-rodentium-subverts-atp-flux-and-cholesterol-homeostasis-in-intestinal-epithelial-cells-in%C3%A2-vivo
#2
Cedric N Berger, Valerie F Crepin, Theodoros I Roumeliotis, James C Wright, Danielle Carson, Meirav Pevsner-Fischer, R Christopher D Furniss, Gordon Dougan, Mally Bachash, Lu Yu, Abigail Clements, James W Collins, Eran Elinav, Gerald J Larrouy-Maumus, Jyoti S Choudhary, Gad Frankel
The intestinal epithelial cells (IECs) that line the gut form a robust line of defense against ingested pathogens. We investigated the impact of infection with the enteric pathogen Citrobacter rodentium on mouse IEC metabolism using global proteomic and targeted metabolomics and lipidomics. The major signatures of the infection were upregulation of the sugar transporter Sglt4, aerobic glycolysis, and production of phosphocreatine, which mobilizes cytosolic energy. In contrast, biogenesis of mitochondrial cardiolipins, essential for ATP production, was inhibited, which coincided with increased levels of mucosal O2 and a reduction in colon-associated anaerobic commensals...
October 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28988823/fgf19-fgf21-and-an-fgfr1-%C3%AE-klotho-activating-antibody-act-on-the-nervous-system-to-regulate-body-weight-and-glycemia
#3
Tian Lan, Donald A Morgan, Kamal Rahmouni, Junichiro Sonoda, Xiaorong Fu, Shawn C Burgess, William L Holland, Steven A Kliewer, David J Mangelsdorf
Despite the different physiologic functions of FGF19 and FGF21 as hormonal regulators of fed and fasted metabolism, their pharmacologic administration causes similar increases in energy expenditure, weight loss, and enhanced insulin sensitivity in obese animals. Here, in genetic loss-of-function studies of the shared co-receptor β-Klotho, we show that these pharmacologic effects are mediated through a common, tissue-specific pathway. Surprisingly, FGF19 and FGF21 actions in liver and adipose tissue are not required for their longer-term weight loss and glycemic effects...
October 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28988822/lipolysis-in-brown-adipocytes-is-not-essential-for-cold-induced-thermogenesis-in-mice
#4
Hyunsu Shin, Yinyan Ma, Tatyana Chanturiya, Qiang Cao, Youlin Wang, Anil K G Kadegowda, Rachel Jackson, Dominic Rumore, Bingzhong Xue, Hang Shi, Oksana Gavrilova, Liqing Yu
Lipid droplet (LD) lipolysis in brown adipose tissue (BAT) is generally considered to be required for cold-induced nonshivering thermogenesis. Here, we show that mice lacking BAT Comparative Gene Identification-58 (CGI-58), a lipolytic activator essential for the stimulated LD lipolysis, have normal thermogenic capacity and are not cold sensitive. Relative to littermate controls, these animals had higher body temperatures when they were provided food during cold exposure. The increase in body temperature in the fed, cold-exposed knockout mice was associated with increased energy expenditure and with increased sympathetic innervation and browning of white adipose tissue (WAT)...
October 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28988821/cold-induced-thermogenesis-depends-on-atgl-mediated-lipolysis-in-cardiac-muscle-but-not-brown-adipose-tissue
#5
Renate Schreiber, Clemens Diwoky, Gabriele Schoiswohl, Ursula Feiler, Nuttaporn Wongsiriroj, Mahmoud Abdellatif, Dagmar Kolb, Joris Hoeks, Erin E Kershaw, Simon Sedej, Patrick Schrauwen, Guenter Haemmerle, Rudolf Zechner
Fatty acids (FAs) activate and fuel UCP1-mediated non-shivering thermogenesis (NST) in brown adipose tissue (BAT). Release of FAs from intracellular fat stores by adipose triglyceride lipase (ATGL) is considered a key step in NST. Accordingly, the severe cold intolerance of global ATGL knockout (AKO) mice has been attributed to defective BAT lipolysis. Here we show that this conclusion is incorrect. We demonstrate that although the BAT-specific loss of ATGL impairs BAT lipolysis and alters BAT morphology, it does not compromise the β3-adrenergic thermogenic response or cold-induced NST...
October 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28988820/atf4-induced-metabolic-reprograming-is-a-synthetic-vulnerability-of-the-p62-deficient-tumor-stroma
#6
Juan F Linares, Thekla Cordes, Angeles Duran, Miguel Reina-Campos, Tania Valencia, Christopher S Ahn, Elias A Castilla, Jorge Moscat, Christian M Metallo, Maria T Diaz-Meco
Tumors undergo nutrient stress and need to reprogram their metabolism to survive. The stroma may play a critical role in this process by providing nutrients to support the epithelial compartment of the tumor. Here we show that p62 deficiency in stromal fibroblasts promotes resistance to glutamine deprivation by the direct control of ATF4 stability through its p62-mediated polyubiquitination. ATF4 upregulation by p62 deficiency in the stroma activates glucose carbon flux through a pyruvate carboxylase-asparagine synthase cascade that results in asparagine generation as a source of nitrogen for stroma and tumor epithelial proliferation...
September 27, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28965825/the-glia-neuron-lactate-shuttle-and-elevated-ros-promote-lipid-synthesis-in-neurons-and-lipid-droplet-accumulation-in-glia-via-apoe-d
#7
Lucy Liu, Kevin R MacKenzie, Nagireddy Putluri, Mirjana Maletić-Savatić, Hugo J Bellen
Elevated reactive oxygen species (ROS) induce the formation of lipids in neurons that are transferred to glia, where they form lipid droplets (LDs). We show that glial and neuronal monocarboxylate transporters (MCTs), fatty acid transport proteins (FATPs), and apolipoproteins are critical for glial LD formation. MCTs enable glia to secrete and neurons to absorb lactate, which is converted to pyruvate and acetyl-CoA in neurons. Lactate metabolites provide a substrate for synthesis of fatty acids, which are processed and transferred to glia by FATP and apolipoproteins...
September 27, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28918935/dense-intra-adipose-sympathetic-arborizations-are-essential-for-cold-induced-beiging-of-mouse-white-adipose-tissue
#8
Haochen Jiang, Xiaofan Ding, Ying Cao, Huanhuan Wang, Wenwen Zeng
Efferent signals from the central nervous system represent a key layer of regulation of white adipose tissue (WAT). However, the mechanism by which efferent neural signals control WAT metabolism remains to be better understood. Here, we exploit the volume fluorescence-imaging technique to visualize the neural arborizations in mouse inguinal WAT at single-fiber resolution. The imaging reveals a dense network of sympathetic arborizations that had been previously undetected by conventional methods, with sympathetic fibers being in close apposition to > 90% of adipocytes...
September 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28889951/pancreatic-%C3%AE-cell-regeneration-as-a-possible-therapy-for-diabetes
#9
REVIEW
Cristina Aguayo-Mazzucato, Susan Bonner-Weir
Diabetes is the result of having inadequate supply of functional insulin-producing β cells. Two possible approaches for replenishing the β cells are: (1) replacement by transplanting cadaveric islets or β cells derived from human embryonic stem cells/induced pluripotent stem cells and (2) induction of endogenous regeneration. This review focuses on endogenous regeneration, which can follow two pathways: enhanced replication of existing β cells and formation of new β cells from cells not expressing insulin, either by conversion from a differentiated cell type (transdifferentiation) or differentiation from progenitors (neogenesis)...
September 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28889950/exploring-metabolic-configurations-of-single-cells-within-complex-tissue-microenvironments
#10
Anne Miller, Csörsz Nagy, Bernhard Knapp, Johannes Laengle, Elisabeth Ponweiser, Marion Groeger, Philipp Starkl, Michael Bergmann, Oswald Wagner, Arvand Haschemi
Over the past years, plenty of evidence has emerged illustrating how metabolism supports many aspects of cellular function and how metabolic reprogramming can drive cell differentiation and fate. Here, we present a method to assess the metabolic configuration of single cells within their native tissue microenvironment via the visualization and quantification of multiple enzymatic activities measured at saturating substrate conditions combined with subsequent cell type identification. After careful validation of the approach and to demonstrate its potential, we assessed the intracellular metabolic configuration of different human immune cell populations in healthy and tumor colon tissue...
September 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28867301/nonalcoholic-fatty-liver-disease-as-a-nexus-of-metabolic-and-hepatic-diseases
#11
REVIEW
Varman T Samuel, Gerald I Shulman
NAFLD is closely linked with hepatic insulin resistance. Accumulation of hepatic diacylglycerol activates PKC-ε, impairing insulin receptor activation and insulin-stimulated glycogen synthesis. Peripheral insulin resistance indirectly influences hepatic glucose and lipid metabolism by increasing flux of substrates that promote lipogenesis (glucose and fatty acids) and gluconeogenesis (glycerol and fatty acid-derived acetyl-CoA, an allosteric activator of pyruvate carboxylase). Weight loss with diet or bariatric surgery effectively treats NAFLD, but drugs specifically approved for NAFLD are not available...
August 29, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28844879/creatine-fuels-the-thermic-effect-of-feeding
#12
Alan R Saltiel
The current obesity epidemic has focused a great deal of attention on cellular pathways of energy expenditure. While a crucial part of this process is diet-induced thermogenesis, the underlying mechanisms have remained unexplained. In this issue of Cell Metabolism, Kazak et al. (2017) describe a new thermogenic pathway in adipocytes that responds to diet overload, involving creatine cycling. These data suggest that this pathway might limit weight gain during overnutrition.
August 17, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28978428/genetic-depletion-of-adipocyte-creatine-metabolism-inhibits-diet-induced-thermogenesis-and-drives-obesity
#13
Lawrence Kazak, Edward T Chouchani, Gina Z Lu, Mark P Jedrychowski, Curtis J Bare, Amir I Mina, Manju Kumari, Song Zhang, Ivan Vuckovic, Dina Laznik-Bogoslavski, Petras Dzeja, Alexander S Banks, Evan D Rosen, Bruce M Spiegelman
No abstract text is available yet for this article.
October 3, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28978427/myc-and-mcl1-cooperatively-promote-chemotherapy-resistant-breast-cancer-stem-cells-via-regulation-of-mitochondrial-oxidative-phosphorylation
#14
Kyung-Min Lee, Jennifer M Giltnane, Justin M Balko, Luis J Schwarz, Angel L Guerrero-Zotano, Katherine E Hutchinson, Mellissa J Nixon, Mónica V Estrada, Violeta Sánchez, Melinda E Sanders, Taekyu Lee, Henry Gómez, Ana Lluch, J Alejandro Pérez-Fidalgo, Melissa Magdalene Wolf, Gabriela Andrejeva, Jeffrey C Rathmell, Stephen W Fesik, Carlos L Arteaga
Most patients with advanced triple-negative breast cancer (TNBC) develop drug resistance. MYC and MCL1 are frequently co-amplified in drug-resistant TNBC after neoadjuvant chemotherapy. Herein, we demonstrate that MYC and MCL1 cooperate in the maintenance of chemotherapy-resistant cancer stem cells (CSCs) in TNBC. MYC and MCL1 increased mitochondrial oxidative phosphorylation (mtOXPHOS) and the generation of reactive oxygen species (ROS), processes involved in maintenance of CSCs. A mutant of MCL1 that cannot localize in mitochondria reduced mtOXPHOS, ROS levels, and drug-resistant CSCs without affecting the anti-apoptotic function of MCL1...
October 3, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28978426/improvement-of-insulin-sensitivity-after-lean-donor-feces-in-metabolic-syndrome-is-driven-by-baseline-intestinal-microbiota-composition
#15
Ruud S Kootte, Evgeni Levin, Jarkko Salojärvi, Loek P Smits, Annick V Hartstra, Shanti D Udayappan, Gerben Hermes, Kristien E Bouter, Annefleur M Koopen, Jens J Holst, Filip K Knop, Ellen E Blaak, Jing Zhao, Hauke Smidt, Amy C Harms, Thomas Hankemeijer, Jacques J G H M Bergman, Hans A Romijn, Frank G Schaap, Steven W M Olde Damink, Mariette T Ackermans, Geesje M Dallinga-Thie, Erwin Zoetendal, Willem M de Vos, Mireille J Serlie, Erik S G Stroes, Albert K Groen, Max Nieuwdorp
The intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We therefore studied the effect of lean donor (allogenic) versus own (autologous) fecal microbiota transplantation (FMT) to male recipients with the metabolic syndrome. Whereas we did not observe metabolic changes at 18 weeks after FMT, insulin sensitivity at 6 weeks after allogenic FMT was significantly improved, accompanied by altered microbiota composition. We also observed changes in plasma metabolites such as γ-aminobutyric acid and show that metabolic response upon allogenic FMT (defined as improved insulin sensitivity 6 weeks after FMT) is dependent on decreased fecal microbial diversity at baseline...
October 3, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28978425/antigen-specific-peptide-immunotherapy-for-type-1-diabetes-proof-of-safety-hope-for-efficacy
#16
Ken Coppieters, Matthias von Herrath
Antigen-specific immunotherapy has long been hailed as the ideal disease-modifying approach for type 1 diabetes, both for disease prevention and reversal. A small phase 1 trial now demonstrates safety of a peptide-based treatment in recently diagnosed adults.
October 3, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28978424/slowing-down-aging
#17
Katharina Meyer, Bruce A Yankner
The hypothalamus plays a key role in coordinating the physiological changes that underlie mammalian aging. In a recent issue of Nature, Cai and colleagues (2017) shed new light on the mechanism of this effect by providing evidence that hypothalamic stem cells may regulate aging through the release of microRNAs in exosomes.
October 3, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28978423/trem2-keeping-microglia-fit-during-good-times-and-bad
#18
Soyon Hong, Beth Stevens
Microglia are the macrophages of the brain and play an important role in Alzheimer's disease (AD). In Cell, Ulland et al. (2017) recently reported that mutations in TREM2, a protein implicated in AD, disrupt microglial energy state and function, thus sabotaging the microglia's ability to defend the brain against amyloid plaques.
October 3, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28978422/the-burgeoning-world-of-immunometabolites-th17-cells-take-center-stage
#19
Glenn R Bantug, Christoph Hess
Dysregulation of the Th17/Treg balance is a key driver of autoimmunity. A new study by Xu et al. (2017) has revealed that small-molecule inhibition of 2-hydroxyglutarate synthesis skews Th17 differentiation to the Treg lineage, which is protective against autoimmune inflammation.
October 3, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28978421/dietary-carbohydrates-impair-healthspan-and-promote-mortality
#20
Meenakshi Ravichandran, Gerald Grandl, Michael Ristow
The prospective cohort study, named PURE, found that in >135,000 participants from 18 countries, nutritive carbohydrates increase human mortality, whereas dietary fat reduces it, requesting a fundamental change of current nutritional guidelines. Experimental evidence from animal models provides synergizing mechanistic concepts as well as pharmacological options to mimic low-carb or ketogenic diets.
October 3, 2017: Cell Metabolism
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