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Cell Metabolism

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https://www.readbyqxmd.com/read/28416194/foxp3-reprograms-t-cell-metabolism-to-function-in-low-glucose-high-lactate-environments
#1
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...
April 11, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380385/palatability-can-drive-feeding-independent-of-agrp-neurons
#2
Raphaël G P Denis, Aurélie Joly-Amado, Emily Webber, Fanny Langlet, Marie Schaeffer, Stéphanie L Padilla, Céline Cansell, Bénédicte Dehouck, Julien Castel, Anne-Sophie Delbès, Sarah Martinez, Amélie Lacombe, Claude Rouch, Nadim Kassis, Jean-Alain Fehrentz, Jean Martinez, Pascal Verdié, Thomas S Hnasko, Richard D Palmiter, Michael J Krashes, Ali D Güler, Christophe Magnan, Serge Luquet
No abstract text is available yet for this article.
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380384/clock-regulation-of-metabolites-reveals-coupling-between-transcription-and-metabolism
#3
Saikumari Y Krishnaiah, Gang Wu, Brian J Altman, Jacqueline Growe, Seth D Rhoades, Faith Coldren, Anand Venkataraman, Anthony O Olarerin-George, Lauren J Francey, Sarmistha Mukherjee, Saiveda Girish, Christopher P Selby, Sibel Cal, Ubeydullah Er, Bahareh Sianati, Arjun Sengupta, Ron C Anafi, I Halil Kavakli, Aziz Sancar, Joseph A Baur, Chi V Dang, John B Hogenesch, Aalim M Weljie
The intricate connection between the circadian clock and metabolism remains poorly understood. We used high temporal resolution metabolite profiling to explore clock regulation of mouse liver and cell-autonomous metabolism. In liver, ∼50% of metabolites were circadian, with enrichment of nucleotide, amino acid, and methylation pathways. In U2 OS cells, 28% were circadian, including amino acids and NAD biosynthesis metabolites. Eighteen metabolites oscillated in both systems and a subset of these in primary hepatocytes...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380383/using-dna-methylation-profiling-to-evaluate-biological-age-and-longevity-interventions
#4
Daniel A Petkovich, Dmitriy I Podolskiy, Alexei V Lobanov, Sang-Goo Lee, Richard A Miller, Vadim N Gladyshev
The DNA methylation levels of certain CpG sites are thought to reflect the pace of human aging. Here, we developed a robust predictor of mouse biological age based on 90 CpG sites derived from partial blood DNA methylation profiles. The resulting clock correctly determines the age of mouse cohorts, detects the longevity effects of calorie restriction and gene knockouts, and reports rejuvenation of fibroblast-derived iPSCs. The data show that mammalian DNA methylomes are characterized by CpG sites that may represent the organism's biological age...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380382/a-single-adaptable-cochaperone-scaffold-complex-delivers-nascent-iron-sulfur-clusters-to-mammalian-respiratory-chain-complexes-i-iii
#5
Nunziata Maio, Ki Soon Kim, Anamika Singh, Tracey A Rouault
The iron-sulfur (Fe-S) cluster of the Rieske protein, UQCRFS1, is essential for Complex III (CIII) activity, though the mechanism for Fe-S cluster transfer has not previously been elucidated. Recent studies have shown that the co-chaperone HSC20, essential for Fe-S cluster biogenesis of SDHB, directly binds LYRM7, formerly described as a chaperone that stabilizes UQCRFS1 prior to its insertion into CIII. Here we report that a transient subcomplex involved in CIII assembly, composed of LYRM7 bound to UQCRFS1, interacts with components of an Fe-S transfer complex, consisting of HSC20, its cognate chaperone HSPA9, and the holo-scaffold ISCU...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380381/fgf21-regulates-metabolism-through-adipose-dependent-and-independent-mechanisms
#6
Lucas D BonDurant, Magdalene Ameka, Meghan C Naber, Kathleen R Markan, Sharon O Idiga, Michael R Acevedo, Susan A Walsh, David M Ornitz, Matthew J Potthoff
FGF21 is an endocrine hormone that regulates energy homeostasis and insulin sensitivity. The mechanism of FGF21 action and the tissues responsible for these effects have been controversial, with both adipose tissues and the central nervous system having been identified as the target site mediating FGF21-dependent increases in insulin sensitivity, energy expenditure, and weight loss. Here we show that, while FGF21 signaling to adipose tissue is required for the acute insulin-sensitizing effects of FGF21, FGF21 signaling to adipose tissue is not required for its chronic effects to increase energy expenditure and lower body weight...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380380/virgin-beta-cells-persist-throughout-life-at-a-neogenic-niche-within-pancreatic-islets
#7
Talitha van der Meulen, Alex M Mawla, Michael R DiGruccio, Michael W Adams, Vera Nies, Sophie Dólleman, Siming Liu, Amanda M Ackermann, Elena Cáceres, Anna E Hunter, Klaus H Kaestner, Cynthia J Donaldson, Mark O Huising
Postnatal maintenance or regeneration of pancreatic beta cells is considered to occur exclusively via the replication of existing beta cells, but clinically meaningful restoration of human beta cell mass by proliferation has never been achieved. We discovered a population of immature beta cells that is present throughout life and forms from non-beta precursors at a specialized micro-environment or "neogenic niche" at the islet periphery. These cells express insulin, but lack other key beta cell markers, and are transcriptionally immature, incapable of sensing glucose, and unable to support calcium influx...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380379/%C3%AE-cell-aging-markers-have-heterogeneous-distribution-and-are-induced-by-insulin-resistance
#8
Cristina Aguayo-Mazzucato, Mark van Haaren, Magdalena Mruk, Terence B Lee, Caitlin Crawford, Jennifer Hollister-Lock, Brooke A Sullivan, James W Johnson, Aref Ebrahimi, Jonathan M Dreyfuss, Jan Van Deursen, Gordon C Weir, Susan Bonner-Weir
We hypothesized that the known heterogeneity of pancreatic β cells was due to subpopulations of β cells at different stages of their life cycle with different functional capacities and that further changes occur with metabolic stress and aging. We identified new markers of aging in β cells, including IGF1R. In β cells IGF1R expression correlated with age, dysfunction, and expression of known age markers p16(ink4a), p53BP1, and senescence-associated β-galactosidase. The new markers showed striking heterogeneity both within and between islets in both mouse and human pancreas...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380378/targeting-abl-ire1%C3%AE-signaling-spares-er-stressed-pancreatic-%C3%AE-cells-to-reverse-autoimmune-diabetes
#9
Shuhei Morita, S Armando Villalta, Hannah C Feldman, Ames C Register, Wendy Rosenthal, Ingeborg T Hoffmann-Petersen, Morvarid Mehdizadeh, Rajarshi Ghosh, Likun Wang, Kevin Colon-Negron, Rosa Meza-Acevedo, Bradley J Backes, Dustin J Maly, Jeffrey A Bluestone, Feroz R Papa
In cells experiencing unrelieved endoplasmic reticulum (ER) stress, the ER transmembrane kinase/endoribonuclease (RNase)-IRE1α-endonucleolytically degrades ER-localized mRNAs to promote apoptosis. Here we find that the ABL family of tyrosine kinases rheostatically enhances IRE1α's enzymatic activities, thereby potentiating ER stress-induced apoptosis. During ER stress, cytosolic ABL kinases localize to the ER membrane, where they bind, scaffold, and hyperactivate IRE1α's RNase. Imatinib-an anti-cancer tyrosine kinase inhibitor-antagonizes the ABL-IRE1α interaction, blunts IRE1α RNase hyperactivity, reduces pancreatic β cell apoptosis, and reverses type 1 diabetes (T1D) in the non-obese diabetic (NOD) mouse model...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380377/farnesoid-x-receptor-regulation-of-the-nlrp3-inflammasome-underlies-cholestasis-associated-sepsis
#10
Haiping Hao, Lijuan Cao, Changtao Jiang, Yuan Che, Songyang Zhang, Shogo Takahashi, Guangji Wang, Frank J Gonzalez
Cholestasis is a common complication of sepsis, and the increased plasma levels of bile acids are predictive of sepsis-associated mortality. However, the exact mechanism by which cholestasis aggravates sepsis development remains elusive. Here, we show that bile acids are danger-associated molecular patterns (DAMPs) that can activate both signal 1 and 2 of the NLRP3 inflammasome in inflammatory macrophages. Mechanistically, bile acids induce a prolonged calcium influx and activate the NLRP3 inflammasome synergistically with ATP...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380376/sirt4-is-a-lysine-deacylase-that-controls-leucine-metabolism-and-insulin-secretion
#11
Kristin A Anderson, Frank K Huynh, Kelsey Fisher-Wellman, J Darren Stuart, Brett S Peterson, Jonathan D Douros, Gregory R Wagner, J Will Thompson, Andreas S Madsen, Michelle F Green, R Michael Sivley, Olga R Ilkayeva, Robert D Stevens, Donald S Backos, John A Capra, Christian A Olsen, Jonathan E Campbell, Deborah M Muoio, Paul A Grimsrud, Matthew D Hirschey
Sirtuins are NAD(+)-dependent protein deacylases that regulate several aspects of metabolism and aging. In contrast to the other mammalian sirtuins, the primary enzymatic activity of mitochondrial sirtuin 4 (SIRT4) and its overall role in metabolic control have remained enigmatic. Using a combination of phylogenetics, structural biology, and enzymology, we show that SIRT4 removes three acyl moieties from lysine residues: methylglutaryl (MG)-, hydroxymethylglutaryl (HMG)-, and 3-methylglutaconyl (MGc)-lysine...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380375/a-class-of-reactive-acyl-coa-species-reveals-the-non-enzymatic-origins-of-protein-acylation
#12
Gregory R Wagner, Dhaval P Bhatt, Thomas M O'Connell, J Will Thompson, Laura G Dubois, Donald S Backos, Hao Yang, Grant A Mitchell, Olga R Ilkayeva, Robert D Stevens, Paul A Grimsrud, Matthew D Hirschey
The mechanisms underlying the formation of acyl protein modifications remain poorly understood. By investigating the reactivity of endogenous acyl-CoA metabolites, we found a class of acyl-CoAs that undergo intramolecular catalysis to form reactive intermediates that non-enzymatically modify proteins. Based on this mechanism, we predicted, validated, and characterized a protein modification: 3-hydroxy-3-methylglutaryl(HMG)-lysine. In a model of altered HMG-CoA metabolism, we found evidence of two additional protein modifications: 3-methylglutaconyl(MGc)-lysine and 3-methylglutaryl(MG)-lysine...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380374/mitochondrial-patch-clamp-of-beige-adipocytes-reveals-ucp1-positive-and-ucp1-negative-cells-both-exhibiting-futile-creatine-cycling
#13
Ambre M Bertholet, Lawrence Kazak, Edward T Chouchani, Marta G Bogaczyńska, Ishan Paranjpe, Gabrielle L Wainwright, Alexandre Bétourné, Shingo Kajimura, Bruce M Spiegelman, Yuriy Kirichok
Cold and other environmental factors induce "browning" of white fat depots-development of beige adipocytes with morphological and functional resemblance to brown fat. Similar to brown fat, beige adipocytes are assumed to express mitochondrial uncoupling protein 1 (UCP1) and are thermogenic due to the UCP1-mediated H(+) leak across the inner mitochondrial membrane. However, this assumption has never been tested directly. Herein we patch clamped the inner mitochondrial membrane of beige and brown fat to provide a direct comparison of their thermogenic H(+) leak (IH)...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380373/imbalanced-insulin-actions-in-obesity-and-type-2-diabetes-key-mouse-models-of-insulin-signaling-pathway
#14
REVIEW
Tetsuya Kubota, Naoto Kubota, Takashi Kadowaki
Since the discovery of the tyrosine kinase activity of the insulin receptor (IR), researchers have been engaged in intensive efforts to resolve physiological functions of IR and its major downstream targets, insulin receptor substrate 1 (Irs1) and Irs2. Studies conducted using systemic and tissue-specific gene-knockout mice of IR, Irs1, and Irs2 have revealed the physiological roles of these molecules in each tissue and interactions among multiple tissues. In obesity and type 2 diabetes, selective downregulation of Irs2 and its downstream actions to cause reduced insulin actions was associated with increased insulin actions through Irs1 in variety tissues...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380372/gpcr-mediated-signaling-of-metabolites
#15
REVIEW
Anna Sofie Husted, Mette Trauelsen, Olga Rudenko, Siv A Hjorth, Thue W Schwartz
In addition to their bioenergetic intracellular function, several classical metabolites act as extracellular signaling molecules activating cell-surface G-protein-coupled receptors (GPCRs), similar to hormones and neurotransmitters. "Signaling metabolites" generated from nutrients or by gut microbiota target primarily enteroendocrine, neuronal, and immune cells in the lamina propria of the gut mucosa and the liver and, through these tissues, the rest of the body. In contrast, metabolites from the intermediary metabolism act mainly as metabolic stress-induced autocrine and paracrine signals in adipose tissue, the liver, and the endocrine pancreas...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380371/the-enigma-of-the-respiratory-chain-supercomplex
#16
REVIEW
Dusanka Milenkovic, James N Blaza, Nils-Göran Larsson, Judy Hirst
Respiratory chain dysfunction plays an important role in human disease and aging. It is now well established that the individual respiratory complexes can be organized into supercomplexes, and structures for these macromolecular assemblies, determined by electron cryo-microscopy, have been described recently. Nevertheless, the reason why supercomplexes exist remains an enigma. The widely held view that they enhance catalysis by channeling substrates is challenged by both structural and biophysical information...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380370/a-novel-protective-role-for-fxr-against-inflammasome-activation-and-endotoxemia
#17
Oihane Garcia-Irigoyen, Antonio Moschetta
During conditions of impaired bile flow (cholestasis), increased serum bile acids (BAs) are prognostic markers of sepsis. In this issue, Hao et al. (2017) show that the BA receptor FXR binds NLRP3 inflammasome in macrophages and inhibits activation of inflammasome components, thus reducing endotoxemia in cholestasis.
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380369/now-ucp-rotein-now-you-don-t-ucp1-is-not-mandatory-for-thermogenesis
#18
Ildiko Szabo, Mario Zoratti
Adipocyte-targeted therapies could potentially combat obesity and metabolic disorders; however, our understanding of adipogenesis and the characterization of the various adipose tissues are incomplete. In this issue, Bertholet et al. (2017) report the existence of two types of heat-producing beige-like adipocytes, those with and those without the mitochondrial uncoupling protein 1 (UCP1).
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380368/brown-fat-derived-exosomes-small-vesicles-with-big-impact
#19
Yong Chen, Alexander Pfeifer
Adipose tissue (AT) not only stores energy, but also secretes hormones and releases small vesicles known as exosomes. Thomou et al. (2017) now show that exosomes secreted by brown fat carry miRNAs that regulate the liver. Thus, AT exosomes might have therapeutic and diagnostic relevance for metabolic disorders.
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380367/pancreas-and-not-gut-mediates-the-glp-1-induced-glucoincretin-effect
#20
Joel F Habener, Violeta Stanojevic
The gut is believed to be the source of GLP-1 that augments insulin secretion in response to oral nutrients. In this issue of Cell Metabolism, Chambers et al. (2017) shift the paradigm by finding that GLP-1 produced within the islets of the pancreas, and not the gut, is responsible for the incretin effect in mice.
April 4, 2017: Cell Metabolism
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