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Cell Metabolism

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https://www.readbyqxmd.com/read/28625867/understanding-the-holobiont-how-microbial-metabolites-affect-human-health-and-shape-the-immune-system
#1
REVIEW
Thomas Siegmund Postler, Sankar Ghosh
The human gastrointestinal tract is populated by a diverse, highly mutualistic microbial flora, which is known as the microbiome. Disruptions to the microbiome have been shown to be associated with severe pathologies of the host, including metabolic disease, cancer, and inflammatory bowel disease. Mood and behavior are also susceptible to alterations in the gut microbiota. A particularly striking example of the symbiotic effects of the microbiome is the immune system, whose cells depend critically on a diverse array of microbial metabolites for normal development and behavior...
June 14, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28506519/sodium-glucose-co-transporters-and-their-inhibition-clinical-physiology
#2
REVIEW
Ele Ferrannini
Sodium-glucose cotransporter-2 (SGLT2) is selectively expressed in the human kidney, where it executes reabsorption of filtered glucose with a high capacity; it may be overactive in patients with diabetes, especially in the early, hyperfiltering stage of the disease. As a therapeutic target, SGLT2 has been successfully engaged by orally active, selective agents. Initially developed as antihyperglycemic drugs, SGLT2 inhibitors have deployed a range of in vivo actions. Consequences of their primary effect, i...
May 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28591639/mitochondrial-dynamics-mediated-by-mitofusin-1-is-required-for-pomc-neuron-glucose-sensing-and-insulin-release-control
#3
Sara Ramírez, Alicia G Gómez-Valadés, Marc Schneeberger, Luis Varela, Roberta Haddad-Tóvolli, Jordi Altirriba, Eduard Noguera, Anne Drougard, Álvaro Flores-Martínez, Mónica Imbernón, Iñigo Chivite, Macarena Pozo, Andrés Vidal-Itriago, Ainhoa Garcia, Sara Cervantes, Rosa Gasa, Ruben Nogueiras, Pau Gama-Pérez, Pablo M Garcia-Roves, David A Cano, Claude Knauf, Joan-Marc Servitja, Tamas L Horvath, Ramon Gomis, Antonio Zorzano, Marc Claret
Proopiomelanocortin (POMC) neurons are critical sensors of nutrient availability implicated in energy balance and glucose metabolism control. However, the precise mechanisms underlying nutrient sensing in POMC neurons remain incompletely understood. We show that mitochondrial dynamics mediated by Mitofusin 1 (MFN1) in POMC neurons couple nutrient sensing with systemic glucose metabolism. Mice lacking MFN1 in POMC neurons exhibited defective mitochondrial architecture remodeling and attenuated hypothalamic gene expression programs during the fast-to-fed transition...
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28591638/interrupted-glucagon-signaling-reveals-hepatic-%C3%AE-cell-axis-and-role-for-l-glutamine-in-%C3%AE-cell-proliferation
#4
E Danielle Dean, Mingyu Li, Nripesh Prasad, Scott N Wisniewski, Alison Von Deylen, Jason Spaeth, Lisette Maddison, Anthony Botros, Leslie R Sedgeman, Nadejda Bozadjieva, Olga Ilkayeva, Anastasia Coldren, Greg Poffenberger, Alena Shostak, Michael C Semich, Kristie I Aamodt, Neil Phillips, Hai Yan, Ernesto Bernal-Mizrachi, Jackie D Corbin, Kasey C Vickers, Shawn E Levy, Chunhua Dai, Christopher Newgard, Wei Gu, Roland Stein, Wenbiao Chen, Alvin C Powers
Decreasing glucagon action lowers the blood glucose and may be useful therapeutically for diabetes. However, interrupted glucagon signaling leads to α cell proliferation. To identify postulated hepatic-derived circulating factor(s) responsible for α cell proliferation, we used transcriptomics/proteomics/metabolomics in three models of interrupted glucagon signaling and found that proliferation of mouse, zebrafish, and human α cells was mTOR and FoxP transcription factor dependent. Changes in hepatic amino acid (AA) catabolism gene expression predicted the observed increase in circulating AAs...
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28591637/amino-acid-transporter-slc38a5-controls-glucagon-receptor-inhibition-induced-pancreatic-%C3%AE-cell-hyperplasia-in-mice
#5
Jinrang Kim, Haruka Okamoto, ZhiJiang Huang, Guillermo Anguiano, Shiuhwei Chen, Qing Liu, Katie Cavino, Yurong Xin, Erqian Na, Rachid Hamid, Joseph Lee, Brian Zambrowicz, Roger Unger, Andrew J Murphy, Yan Xu, George D Yancopoulos, Wen-Hong Li, Jesper Gromada
Glucagon supports glucose homeostasis by stimulating hepatic gluconeogenesis, in part by promoting the uptake and conversion of amino acids into gluconeogenic precursors. Genetic disruption or pharmacologic inhibition of glucagon signaling results in elevated plasma amino acids and compensatory glucagon hypersecretion involving expansion of pancreatic α cell mass. Recent findings indicate that hyperaminoacidemia triggers pancreatic α cell proliferation via an mTOR-dependent pathway. We confirm and extend these findings by demonstrating that glucagon pathway blockade selectively increases expression of the sodium-coupled neutral amino acid transporter Slc38a5 in a subset of highly proliferative α cells and that Slc38a5 controls the pancreatic response to glucagon pathway blockade; most notably, mice deficient in Slc38a5 exhibit markedly decreased α cell hyperplasia to glucagon pathway blockade-induced hyperaminoacidemia...
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28591636/n-acyl-taurines-and-acylcarnitines-cause-an-imbalance-in-insulin-synthesis-and-secretion-provoking-%C3%AE-cell-dysfunction-in-type-2-diabetes
#6
Michaela Aichler, Daniela Borgmann, Jan Krumsiek, Achim Buck, Patrick E MacDonald, Jocelyn E Manning Fox, James Lyon, Peter E Light, Susanne Keipert, Martin Jastroch, Annette Feuchtinger, Nikola S Mueller, Na Sun, Andrew Palmer, Theodore Alexandrov, Martin Hrabe de Angelis, Susanne Neschen, Matthias H Tschöp, Axel Walch
The processes contributing to β cell dysfunction in type 2 diabetes (T2D) are uncertain, largely because it is difficult to access β cells in their intact immediate environment. We examined the pathophysiology of β cells under T2D progression directly in pancreatic tissues. We used MALDI imaging of Langerhans islets (LHIs) within mouse tissues or from human tissues to generate in situ-omics data, which we supported with in vitro experiments. Molecular interaction networks provided information on functional pathways and molecules...
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28591635/hypothalamic-pituitary-axis-regulates-hydrogen-sulfide-production
#7
Christopher Hine, Hyo-Jeong Kim, Yan Zhu, Eylul Harputlugil, Alban Longchamp, Marina Souza Matos, Preeti Ramadoss, Kevin Bauerle, Lear Brace, John M Asara, C Keith Ozaki, Sheue-Yann Cheng, Subhankar Singha, Kyo Han Ahn, Alec Kimmelman, Ffolliott M Fisher, Pavlos Pissios, Dominic J Withers, Colin Selman, Rui Wang, Kelvin Yen, Valter D Longo, Pinchas Cohen, Andrzej Bartke, John J Kopchick, Richard Miller, Anthony N Hollenberg, James R Mitchell
Decreased growth hormone (GH) and thyroid hormone (TH) signaling are associated with longevity and metabolic fitness. The mechanisms underlying these benefits are poorly understood, but may overlap with those of dietary restriction (DR), which imparts similar benefits. Recently we discovered that hydrogen sulfide (H2S) is increased upon DR and plays an essential role in mediating DR benefits across evolutionary boundaries. Here we found increased hepatic H2S production in long-lived mouse strains of reduced GH and/or TH action, and in a cell-autonomous manner upon serum withdrawal in vitro...
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28591634/a-cell-autonomous-mammalian-12%C3%A2-hr-clock-coordinates-metabolic-and-stress-rhythms
#8
Bokai Zhu, Qiang Zhang, Yinghong Pan, Emily M Mace, Brian York, Athanasios C Antoulas, Clifford C Dacso, Bert W O'Malley
Besides circadian rhythms, oscillations cycling with a 12 hr period exist. However, the prevalence, origin, regulation, and function of mammalian 12 hr rhythms remain elusive. Utilizing an unbiased mathematical approach identifying all superimposed oscillations, we uncovered prevalent 12 hr gene expression and metabolic rhythms in mouse liver, coupled with a physiological 12 hr unfolded protein response oscillation. The mammalian 12 hr rhythm is cell autonomous, driven by a dedicated 12 hr pacemaker distinct from the circadian clock, and can be entrained in vitro by metabolic and ER stress cues...
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28591633/cytochrome-c-oxidase-activity-is-a-metabolic-checkpoint-that-regulates-cell-fate-decisions-during-t-cell-activation-and-differentiation
#9
Tatyana N Tarasenko, Susan E Pacheco, Mary Kay Koenig, Julio Gomez-Rodriguez, Senta M Kapnick, Francisca Diaz, Patricia M Zerfas, Emanuele Barca, Jessica Sudderth, Ralph J DeBerardinis, Raul Covian, Robert S Balaban, Salvatore DiMauro, Peter J McGuire
T cells undergo metabolic reprogramming with major changes in cellular energy metabolism during activation. In patients with mitochondrial disease, clinical data were marked by frequent infections and immunodeficiency, prompting us to explore the consequences of oxidative phosphorylation dysfunction in T cells. Since cytochrome c oxidase (COX) is a critical regulator of OXPHOS, we created a mouse model with isolated dysfunction in T cells by targeting a gene, COX10, that produces mitochondrial disease in humans...
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28591632/bread-affects-clinical-parameters-and-induces-gut-microbiome-associated-personal-glycemic-responses
#10
Tal Korem, David Zeevi, Niv Zmora, Omer Weissbrod, Noam Bar, Maya Lotan-Pompan, Tali Avnit-Sagi, Noa Kosower, Gal Malka, Michal Rein, Jotham Suez, Ben Z Goldberg, Adina Weinberger, Avraham A Levy, Eran Elinav, Eran Segal
Bread is consumed daily by billions of people, yet evidence regarding its clinical effects is contradicting. Here, we performed a randomized crossover trial of two 1-week-long dietary interventions comprising consumption of either traditionally made sourdough-leavened whole-grain bread or industrially made white bread. We found no significant differential effects of bread type on multiple clinical parameters. The gut microbiota composition remained person specific throughout this trial and was generally resilient to the intervention...
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28591631/gut-brain-glucose-signaling-in-energy-homeostasis
#11
REVIEW
Maud Soty, Amandine Gautier-Stein, Fabienne Rajas, Gilles Mithieux
Intestinal gluconeogenesis is a recently identified function influencing energy homeostasis. Intestinal gluconeogenesis induced by specific nutrients releases glucose, which is sensed by the nervous system surrounding the portal vein. This initiates a signal positively influencing parameters involved in glucose control and energy management controlled by the brain. This knowledge has extended our vision of the gut-brain axis, classically ascribed to gastrointestinal hormones. Our work raises several questions relating to the conditions under which intestinal gluconeogenesis proceeds and may provide its metabolic benefits...
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28591630/a-guide-for-the-design-of-pre-clinical-studies-on-sex-differences-in-metabolism
#12
REVIEW
Franck Mauvais-Jarvis, Arthur P Arnold, Karen Reue
In animal models, the physiological systems involved in metabolic homeostasis exhibit a sex difference. Investigators often use male rodents because they show metabolic disease better than females. Thus, females are not used precisely because of an acknowledged sex difference that represents an opportunity to understand novel factors reducing metabolic disease more in one sex than the other. The National Institutes of Health (NIH) mandate to consider sex as a biological variable in preclinical research places new demands on investigators and peer reviewers who often lack expertise in model systems and experimental paradigms used in the study of sex differences...
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28591629/treg-cells-survive-and-thrive-in-inhospitable-environments
#13
Katarzyna M Grzes, Cameron S Field, Edward J Pearce
Immune responses are dangerous by nature and require regulation to prevent inflammatory and/or autoimmune sequelae and allow healing. CD4(+)Foxp3(+) T cells (Treg cells) play a crucial role in this process, and in this edition of Cell Metabolism, Angelin et al. (2017) describe how these cells are metabolically adapted to the job.
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28591628/type-i-interferons-interfere-with-liver-glucose-metabolism
#14
Güneş Parlakgul, Gökhan S Hotamisligil
The specific immunological components linking metabolic stresses to liver inflammation and systemic metabolic pathologies in obesity are not entirely known. A recent study (Ghazarian et al., 2017) reveals that obesity-induced type I interferon signaling drives the accumulation and activation of intrahepatic CD8(+) T cells, leading to systemic metabolic deterioration.
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28591627/triglyceride-metabolism-under-attack
#15
Sander Kersten
Hydrolysis of circulating triglycerides is carried out by the enzyme lipoprotein lipase, which is transported and anchored to the capillary wall by the protein GPIHBP1. Recent evidence indicates that certain individuals develop autoantibodies against GPIHBP1, impairing lipoprotein lipase function and leading to markedly elevated plasma triglyceride levels (Beigneux et al., 2017).
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28576418/a-methyl-balanced-diet-prevents-crf-induced-prenatal-stress-triggered-predisposition-to-binge-eating-like-phenotype
#16
Mariana Schroeder, Mira Jakovcevski, Tamar Polacheck, Maya Lebow, Yonat Drori, Mareen Engel, Shifra Ben-Dor, Alon Chen
Binge eating (BE) is a common aberrant form of eating behavior, characterized by overconsumption of food in a brief period of time. Recurrent episodes of BE constitute the BE disorder, which mostly affects females and is associated with early-life adversities. Here, we show that corticotropin releasing factor (CRF)-induced prenatal stress (PNS) in late gestation predisposes female offspring to BE-like behavior that coincides with hypomethylation of hypothalamic miR-1a and downstream dysregulation of the melanocortin system through Pax7/Pax3...
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28552492/age-associated-loss-of-opa1-in-muscle-impacts-muscle-mass-metabolic-homeostasis-systemic-inflammation-and-epithelial-senescence
#17
Caterina Tezze, Vanina Romanello, Maria Andrea Desbats, Gian Paolo Fadini, Mattia Albiero, Giulia Favaro, Stefano Ciciliot, Maria Eugenia Soriano, Valeria Morbidoni, Cristina Cerqua, Stefan Loefler, Helmut Kern, Claudio Franceschi, Stefano Salvioli, Maria Conte, Bert Blaauw, Sandra Zampieri, Leonardo Salviati, Luca Scorrano, Marco Sandri
Mitochondrial dysfunction occurs during aging, but its impact on tissue senescence is unknown. Here, we find that sedentary but not active humans display an age-related decline in the mitochondrial protein, optic atrophy 1 (OPA1), that is associated with muscle loss. In adult mice, acute, muscle-specific deletion of Opa1 induces a precocious senescence phenotype and premature death. Conditional and inducible Opa1 deletion alters mitochondrial morphology and function but not DNA content. Mechanistically, the ablation of Opa1 leads to ER stress, which signals via the unfolded protein response (UPR) and FoxOs, inducing a catabolic program of muscle loss and systemic aging...
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28479366/cholesterol-accumulation-in-dendritic-cells-links-the-inflammasome-to-acquired-immunity
#18
Marit Westerterp, Emmanuel L Gautier, Anjali Ganda, Matthew M Molusky, Wei Wang, Panagiotis Fotakis, Nan Wang, Gwendalyn J Randolph, Vivette D D'Agati, Laurent Yvan-Charvet, Alan R Tall
Autoimmune diseases such as systemic lupus erythematosus (SLE) are associated with increased cardiovascular disease and reduced plasma high-density lipoprotein (HDL) levels. HDL mediates cholesterol efflux from immune cells via the ATP binding cassette transporters A1 and G1 (ABCA1/G1). The significance of impaired cholesterol efflux pathways in autoimmunity is unknown. We observed that Abca1/g1-deficient mice develop enlarged lymph nodes (LNs) and glomerulonephritis suggestive of SLE. This lupus-like phenotype was recapitulated in mice with knockouts of Abca1/g1 in dendritic cells (DCs), but not in macrophages or T cells...
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28416194/foxp3-reprograms-t-cell-metabolism-to-function-in-low-glucose-high-lactate-environments
#19
Alessia Angelin, Luis Gil-de-Gómez, Satinder Dahiya, Jing Jiao, Lili Guo, Matthew H Levine, Zhonglin Wang, William J Quinn, Piotr K Kopinski, Liqing Wang, Tatiana Akimova, Yujie Liu, Tricia R Bhatti, Rongxiang Han, Benjamin L Laskin, Joseph A Baur, Ian A Blair, Douglas C Wallace, Wayne W Hancock, Ulf H Beier
Immune cells function in diverse metabolic environments. Tissues with low glucose and high lactate concentrations, such as the intestinal tract or ischemic tissues, frequently require immune responses to be more pro-tolerant, avoiding unwanted reactions against self-antigens or commensal bacteria. T-regulatory cells (Tregs) maintain peripheral tolerance, but how Tregs function in low-glucose, lactate-rich environments is unknown. We report that the Treg transcription factor Foxp3 reprograms T cell metabolism by suppressing Myc and glycolysis, enhancing oxidative phosphorylation, and increasing nicotinamide adenine dinucleotide oxidation...
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28467946/quiescence-like-metabolism-to-push-cancer-out-of-the-race
#20
Verónica Torrano, Arkaitz Carracedo
Biological features acquired or lost during the tumorigenic process are a source for the discovery of molecular cues relevant to cancer. The latest study led by the Weinberg lab (Keckesova et al., 2017) focuses on the transcriptional program underlying quiescence to uncover a novel metabolic tumor suppressor, LACTB.
May 2, 2017: Cell Metabolism
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