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Cell Metabolism

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https://www.readbyqxmd.com/read/28215845/converting-adult-pancreatic-islet-%C3%AE-cells-into-%C3%AE-cells-by-targeting-both-dnmt1-and-arx
#1
Harini Chakravarthy, Xueying Gu, Martin Enge, Xiaoqing Dai, Yong Wang, Nicolas Damond, Carolina Downie, Kathy Liu, Jing Wang, Yuan Xing, Simona Chera, Fabrizio Thorel, Stephen Quake, Jose Oberholzer, Patrick E MacDonald, Pedro L Herrera, Seung K Kim
Insulin-producing pancreatic β cells in mice can slowly regenerate from glucagon-producing α cells in settings like β cell loss, but the basis of this conversion is unknown. Moreover, it remains unclear if this intra-islet cell conversion is relevant to diseases like type 1 diabetes (T1D). We show that the α cell regulators Aristaless-related homeobox (Arx) and DNA methyltransferase 1 (Dnmt1) maintain α cell identity in mice. Within 3 months of Dnmt1 and Arx loss, lineage tracing and single-cell RNA sequencing revealed extensive α cell conversion into progeny resembling native β cells...
February 12, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28215844/excessive-respiratory-modulation-of-blood-pressure-triggers-hypertension
#2
Clément Menuet, Sheng Le, Bowen Dempsey, Angela A Connelly, Jessica L Kamar, Nikola Jancovski, Jaspreet K Bassi, Keryn Walters, Annabel E Simms, Andrew Hammond, Angelina Y Fong, Ann K Goodchild, Simon McMullan, Andrew M Allen
The etiology of hypertension, the world's biggest killer, remains poorly understood, with treatments targeting the established symptom, not the cause. The development of hypertension involves increased sympathetic nerve activity that, in experimental hypertension, may be driven by excessive respiratory modulation. Using selective viral and cell lesion techniques, we identify adrenergic C1 neurons in the medulla oblongata as critical for respiratory-sympathetic entrainment and the development of experimental hypertension...
February 12, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28215843/a-pdgfr%C3%AE-mediated-switch-toward-cd9-high-adipocyte-progenitors-controls-obesity-induced-adipose-tissue-fibrosis
#3
Geneviève Marcelin, Adaliene Ferreira, Yuejun Liu, Michael Atlan, Judith Aron-Wisnewsky, Véronique Pelloux, Yair Botbol, Marc Ambrosini, Magali Fradet, Christine Rouault, Corneliu Hénégar, Jean-Sébastien Hulot, Christine Poitou, Adriana Torcivia, Raphael Nail-Barthelemy, Jean-Christophe Bichet, Emmanuel L Gautier, Karine Clément
Obesity-induced white adipose tissue (WAT) fibrosis is believed to accelerate WAT dysfunction. However, the cellular origin of WAT fibrosis remains unclear. Here, we show that adipocyte platelet-derived growth factor receptor-α-positive (PDGFRα(+)) progenitors adopt a fibrogenic phenotype in obese mice prone to visceral WAT fibrosis. More specifically, a subset of PDGFRα(+) cells with high CD9 expression (CD9(high)) originates pro-fibrotic cells whereas their CD9(low) counterparts, committed to adipogenesis, are almost completely lost in the fibrotic WAT...
February 9, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28190773/%C3%AE-cells-that-resist-immunological-attack-develop-during-progression-of-autoimmune-diabetes-in-nod-mice
#4
Jinxiu Rui, Songyan Deng, Arnon Arazi, Ana Luisa Perdigoto, Zongzhi Liu, Kevan C Herold
Type 1 diabetes (T1D) is a chronic autoimmune disease that involves immune-mediated destruction of β cells. How β cells respond to immune attack is unknown. We identified a population of β cells during the progression of T1D in non-obese diabetic (NOD) mice that survives immune attack. This population develops from normal β cells confronted with islet infiltrates. Pathways involving cell movement, growth and proliferation, immune responses, and cell death and survival are activated in these cells. There is reduced expression of β cell identity genes and diabetes antigens and increased immune inhibitory markers and stemness genes...
February 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28190774/reducing-vegf-b-signaling-ameliorates-renal-lipotoxicity-and-protects-against-diabetic-kidney-disease
#5
Annelie Falkevall, Annika Mehlem, Isolde Palombo, Benjamin Heller Sahlgren, Lwaki Ebarasi, Liqun He, A Jimmy Ytterberg, Hannes Olauson, Jonas Axelsson, Birgitta Sundelin, Jaakko Patrakka, Pierre Scotney, Andrew Nash, Ulf Eriksson
Diabetic kidney disease (DKD) is the most common cause of severe renal disease, and few treatment options are available today that prevent the progressive loss of renal function. DKD is characterized by altered glomerular filtration and proteinuria. A common observation in DKD is the presence of renal steatosis, but the mechanism(s) underlying this observation and to what extent they contribute to disease progression are unknown. Vascular endothelial growth factor B (VEGF-B) controls muscle lipid accumulation through regulation of endothelial fatty acid transport...
February 1, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28190775/drp1-suppresses-leptin-and-glucose-sensing-of-pomc-neurons
#6
Anna Santoro, Michela Campolo, Chen Liu, Hiromi Sesaki, Rosaria Meli, Zhong-Wu Liu, Jung Dae Kim, Sabrina Diano
Hypothalamic pro-opiomelanocortin (POMC) neurons regulate energy and glucose metabolism. Intracellular mechanisms that enable these neurons to respond to changes in metabolic environment are ill defined. Here we show reduced expression of activated dynamin-related protein (pDRP1), a mitochondrial fission regulator, in POMC neurons of fed mice. These POMC neurons displayed increased mitochondrial size and aspect ratio compared to POMC neurons of fasted animals. Inducible deletion of DRP1 of mature POMC neurons (Drp1(fl/fl)-POMC-cre:ER(T2)) resulted in improved leptin sensitivity and glucose responsiveness...
January 30, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28190772/sex-differences-a-resultant-of-an-evolutionary-pressure
#7
Sara Della Torre, Adriana Maggi
Spurred by current research policy, we are witnessing a significant growth in the number of studies that observe and describe sexual diversities in human physiology and sex prevalence in a large number of pathologies. Yet we are far from the comprehension of the mechanisms underpinning these differences, which are the result of a long evolutionary history. This Essay is meant to underline female reproductive function as a driver for the positive selection of the specific physiological features that explain male and female differential susceptibility to diseases and metabolic disturbances, in particular...
January 30, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28190771/obesity-induced-metabolic-stress-leads-to-biased-effector-memory-cd4-t-cell-differentiation-via-pi3k-p110%C3%AE-akt-mediated-signals
#8
Claudio Mauro, Joanne Smith, Danilo Cucchi, David Coe, Hongmei Fu, Fabrizia Bonacina, Andrea Baragetti, Gaia Cermenati, Donatella Caruso, Nico Mitro, Alberico L Catapano, Enrico Ammirati, Maria P Longhi, Klaus Okkenhaug, Giuseppe D Norata, Federica M Marelli-Berg
Low-grade systemic inflammation associated to obesity leads to cardiovascular complications, caused partly by infiltration of adipose and vascular tissue by effector T cells. The signals leading to T cell differentiation and tissue infiltration during obesity are poorly understood. We tested whether saturated fatty acid-induced metabolic stress affects differentiation and trafficking patterns of CD4(+) T cells. Memory CD4(+) T cells primed in high-fat diet-fed donors preferentially migrated to non-lymphoid, inflammatory sites, independent of the metabolic status of the hosts...
January 30, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28162969/parathyroid-hormone-directs-bone-marrow-mesenchymal-cell-fate
#9
Yi Fan, Jun-Ichi Hanai, Phuong T Le, Ruiye Bi, David Maridas, Victoria DeMambro, Carolina A Figueroa, Serkan Kir, Xuedong Zhou, Michael Mannstadt, Roland Baron, Roderick T Bronson, Mark C Horowitz, Joy Y Wu, John P Bilezikian, David W Dempster, Clifford J Rosen, Beate Lanske
Intermittent PTH administration builds bone mass and prevents fractures, but its mechanism of action is unclear. We genetically deleted the PTH/PTHrP receptor (PTH1R) in mesenchymal stem cells using Prx1Cre and found low bone formation, increased bone resorption, and high bone marrow adipose tissue (BMAT). Bone marrow adipocytes traced to Prx1 and expressed classic adipogenic markers and high receptor activator of nuclear factor kappa B ligand (Rankl) expression. RANKL levels were also elevated in bone marrow supernatant and serum, but undetectable in other adipose depots...
January 25, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28132808/store-operated-ca-2-entry-controls-induction-of-lipolysis-and-the-transcriptional-reprogramming-to-lipid-metabolism
#10
Mate Maus, Mario Cuk, Bindi Patel, Jayson Lian, Mireille Ouimet, Ulrike Kaufmann, Jun Yang, Rita Horvath, Hue-Tran Hornig-Do, Zofia M Chrzanowska-Lightowlers, Kathryn J Moore, Ana Maria Cuervo, Stefan Feske
Ca(2+) signals were reported to control lipid homeostasis, but the Ca(2+) channels and pathways involved are largely unknown. Store-operated Ca(2+) entry (SOCE) is a ubiquitous Ca(2+) influx pathway regulated by stromal interaction molecule 1 (STIM1), STIM2, and the Ca(2+) channel ORAI1. We show that SOCE-deficient mice accumulate pathological amounts of lipid droplets in the liver, heart, and skeletal muscle. Cells from patients with loss-of-function mutations in STIM1 or ORAI1 show a similar phenotype, suggesting a cell-intrinsic role for SOCE in the regulation of lipid metabolism...
January 21, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28111213/a-non-invasive-method-to-assess-hepatic-acetyl-coa-in%C3%A2-vivo
#11
Rachel J Perry, Liang Peng, Gary W Cline, Kitt Falk Petersen, Gerald I Shulman
Acetyl-coenzyme A (acetyl-CoA) is a critical metabolic signaling molecule that regulates gluconeogenesis, pyruvate oxidation, protein acetylation, and steroid and fatty acid biosynthesis; however, measurements of this metabolite using standard biochemical approaches are technically demanding, and there is currently no method to non-invasively assess hepatic acetyl-CoA content in vivo. To this end, we developed and validated a method to non-invasively detect differences in hepatic acetyl-CoA content in vivo across a 5-fold range of physiological acetyl-CoA concentrations by assessing the turnover of [(13)C4]β-hydroxybutyrate (β-OHB)...
January 18, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28178570/serine-is-an-essential-metabolite-for-effector-t-cell-expansion
#12
Eric H Ma, Glenn Bantug, Takla Griss, Stephanie Condotta, Radia M Johnson, Bozena Samborska, Nello Mainolfi, Vipin Suri, Hannah Guak, Maria L Balmer, Mark J Verway, Thomas C Raissi, Harmony Tsui, Giselle Boukhaled, Sofia Henriques da Costa, Christian Frezza, Connie M Krawczyk, Adam Friedman, Mark Manfredi, Martin J Richer, Christoph Hess, Russell G Jones
No abstract text is available yet for this article.
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28178569/cellular-aging-contributes-to-failure-of-cold-induced-beige-adipocyte-formation-in-old-mice-and-humans
#13
Daniel C Berry, Yuwei Jiang, Robert W Arpke, Elizabeth L Close, Aki Uchida, David Reading, Eric D Berglund, Michael Kyba, Jonathan M Graff
No abstract text is available yet for this article.
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28178568/midgut-derived-activin-regulates-glucagon-like-action-in-the-fat-body-and-glycemic-control
#14
Wei Song, Daojun Cheng, Shangyu Hong, Benoit Sappe, Yanhui Hu, Neil Wei, Changqi Zhu, Michael B O'Connor, Pavlos Pissios, Norbert Perrimon
While high-caloric diet impairs insulin response to cause hyperglycemia, whether and how counter-regulatory hormones are modulated by high-caloric diet is largely unknown. We find that enhanced response of Drosophila adipokinetic hormone (AKH, the glucagon homolog) in the fat body is essential for hyperglycemia associated with a chronic high-sugar diet. We show that the activin type I receptor Baboon (Babo) autonomously increases AKH signaling without affecting insulin signaling in the fat body via, at least, increase of Akh receptor (AkhR) expression...
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28178567/defective-branched-chain-amino-acid-catabolism-disrupts-glucose-metabolism-and-sensitizes-the-heart-to-ischemia-reperfusion-injury
#15
Tao Li, Zhen Zhang, Stephen C Kolwicz, Lauren Abell, Nathan D Roe, Maengjo Kim, Bo Zhou, Yang Cao, Julia Ritterhoff, Haiwei Gu, Daniel Raftery, Haipeng Sun, Rong Tian
Elevated levels of branched-chain amino acids (BCAAs) have recently been implicated in the development of cardiovascular and metabolic diseases, but the molecular mechanisms are unknown. In a mouse model of impaired BCAA catabolism (knockout [KO]), we found that chronic accumulation of BCAAs suppressed glucose metabolism and sensitized the heart to ischemic injury. High levels of BCAAs selectively disrupted mitochondrial pyruvate utilization through inhibition of pyruvate dehydrogenase complex (PDH) activity...
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28178566/wnk-kinase-signaling-in-ion-homeostasis-and-human-disease
#16
REVIEW
Masoud Shekarabi, Jinwei Zhang, Arjun R Khanna, David H Ellison, Eric Delpire, Kristopher T Kahle
WNK kinases, along with their upstream regulators (CUL3/KLHL3) and downstream targets (the SPAK/OSR1 kinases and the cation-Cl(-) cotransporters [CCCs]), comprise a signaling cascade essential for ion homeostasis in the kidney and nervous system. Recent work has furthered our understanding of the WNKs in epithelial transport, cell volume homeostasis, and GABA signaling, and uncovered novel roles for this pathway in immune cell function and cell proliferation.
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28178565/multi-dimensional-roles-of-ketone-bodies-in-fuel-metabolism-signaling-and-therapeutics
#17
REVIEW
Patrycja Puchalska, Peter A Crawford
Ketone body metabolism is a central node in physiological homeostasis. In this review, we discuss how ketones serve discrete fine-tuning metabolic roles that optimize organ and organism performance in varying nutrient states and protect from inflammation and injury in multiple organ systems. Traditionally viewed as metabolic substrates enlisted only in carbohydrate restriction, observations underscore the importance of ketone bodies as vital metabolic and signaling mediators when carbohydrates are abundant...
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28178564/microbial-molecules-from-the-multitudes-within-us
#18
Matthew R Redinbo
Chemists demonstrate in Cell that intestinal microbes are capable of synthesizing metabolites that look like clinical drugs and inhibit human targets. These results provide molecular resolution to the field of mammalian-microbial mutualism and highlight the potential for natural product discovery from the multitudes within us.
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28178563/lipid-metabolism-fuels-cancer-s-spread
#19
Zhuo Li, Yibin Kang
The ability to prospectively identify metastasis-initiating cells is essential for developing new anti-metastasis therapeutics. In a recent issue of Nature, Pascual et al. (2017) demonstrate that the fatty acid receptor CD36 marks a subpopulation of cancer cells with unique metastasis-initiating potential, highlighting a key role of lipid metabolism in metastatic colonization.
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28178562/young-and-lean-elimination-of-senescent-cells-boosts-adaptive-thermogenesis
#20
Pablo J Fernandez-Marcos, Manuel Serrano
Thermogenesis converts the chemical energy of nutrients into heat, and this is associated to improved metabolic performance. In a previous issue of Cell Metabolism, Berry et al. (2017) reported that the progenitors of thermogenic beige adipocytes lose functionality with aging, and this process can be reversed with strategies that eliminate senescent cells.
February 7, 2017: Cell Metabolism
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