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  • Cytosolic pH regulates proliferation and tumour growth by promoting expression of cyclin D1
    Nat. Metab. Pub Date : 2020-10-19
    Lisa Maria Koch; Eivind Salmorin Birkeland; Stefania Battaglioni; Xiao Helle; Mayura Meerang; Stefanie Hiltbrunner; Alfredo J. Ibáñez; Matthias Peter; Alessandra Curioni-Fontecedro; Isabelle Opitz; Reinhard Dechant

    Enhanced growth and proliferation of cancer cells are accompanied by profound changes in cellular metabolism. These metabolic changes are also common under physiological conditions, and include increased glucose fermentation accompanied by elevated cytosolic pH (pHc)1,2. However, how these changes contribute to enhanced cell growth and proliferation is unclear. Here, we show that elevated pHc specifically

    更新日期:2020-10-19
  • Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals
    Nat. Metab. Pub Date : 2020-10-16
    Lasse Folkersen; Stefan Gustafsson; Qin Wang; Daniel Hvidberg Hansen; Åsa K. Hedman; Andrew Schork; Karen Page; Daria V. Zhernakova; Yang Wu; James Peters; Niclas Eriksson; Sarah E. Bergen; Thibaud S. Boutin; Andrew D. Bretherick; Stefan Enroth; Anette Kalnapenkis; Jesper R. Gådin; Bianca E. Suur; Yan Chen; Ljubica Matic; Jeremy D. Gale; Julie Lee; Weidong Zhang; Amira Quazi; Mika Ala-Korpela; Seung

    Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain

    更新日期:2020-10-17
  • Mind your media
    Nat. Metab. Pub Date : 2020-10-12
    Shoval Lagziel; Eyal Gottlieb; Tomer Shlomi

    Cell culture media are typically selected on the basis of common laboratory practices but have major effects on the validity, reproducibility and physiological relevance of the scientific findings. We provide arguments and quantitative examples of why choosing an appropriate cell culture medium matters, particularly in metabolic studies.

    更新日期:2020-10-12
  • Pathogenic variants in actionable MODY genes are associated with type 2 diabetes
    Nat. Metab. Pub Date : 2020-10-12
    Amélie Bonnefond; Mathilde Boissel; Alexandre Bolze; Emmanuelle Durand; Bénédicte Toussaint; Emmanuel Vaillant; Stefan Gaget; Franck De Graeve; Aurélie Dechaume; Frédéric Allegaert; David Le Guilcher; Loïc Yengo; Véronique Dhennin; Jean-Michel Borys; James T. Lu; Elizabeth T. Cirulli; Gai Elhanan; Ronan Roussel; Beverley Balkau; Michel Marre; Sylvia Franc; Guillaume Charpentier; Martine Vaxillaire;

    Genome-wide association studies have identified 240 independent loci associated with type 2 diabetes (T2D) risk, but this knowledge has not advanced precision medicine. In contrast, the genetic diagnosis of monogenic forms of diabetes (including maturity-onset diabetes of the young (MODY)) are textbook cases of genomic medicine. Recent studies trying to bridge the gap between monogenic diabetes and

    更新日期:2020-10-12
  • Nuclear metabolism and the regulation of the epigenome
    Nat. Metab. Pub Date : 2020-10-12
    Ruben Boon; Giorgia G. Silveira; Raul Mostoslavsky

    Cellular metabolism has emerged as a major biological node governing cellular behaviour. Metabolic pathways fuel cellular energy needs, providing basic chemical molecules to sustain cellular homeostasis, proliferation and function. Changes in nutrient consumption or availability therefore can result in complete reprogramming of cellular metabolism towards stabilizing core metabolite pools, such as

    更新日期:2020-10-12
  • A developmental checkpoint directs metabolic remodelling as a strategy against starvation in Drosophila
    Nat. Metab. Pub Date : 2020-10-12
    Takayuki Yamada; Ken-ichi Hironaka; Okiko Habara; Yoshihiro Morishita; Takashi Nishimura

    Steroid hormones are crucial regulators of life-stage transitions during development in animals. However, the molecular mechanisms by which developmental transition through these stages is coupled with optimal metabolic homeostasis remains poorly understood. Here, we demonstrate through mathematical modelling and experimental validation that ecdysteroid-induced metabolic remodelling from resource consumption

    更新日期:2020-10-12
  • Publisher Correction: RIPK1 gene variants associate with obesity in humans and can be therapeutically silenced to reduce obesity in mice
    Nat. Metab. Pub Date : 2020-10-08
    Denuja Karunakaran; Adam W. Turner; Anne-Claire Duchez; Sebastien Soubeyrand; Adil Rasheed; David Smyth; David P. Cook; Majid Nikpay; Joshua W. Kandiah; Calvin Pan; Michele Geoffrion; Richard Lee; Ludovic Boytard; Hailey Wyatt; My-Anh Nguyen; Paulina Lau; Markku Laakso; Bhama Ramkhelawon; Marcus Alvarez; Kirsi H. Pietiläinen; Päivi Pajukanta; Barbara C. Vanderhyden; Peter Liu; Scott B. Berger; Peter

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-10-11
  • Author Correction: Glis1 facilitates induction of pluripotency via an epigenome–metabolome–epigenome signalling cascade
    Nat. Metab. Pub Date : 2020-10-08
    Linpeng Li; Keshi Chen; Tianyu Wang; Yi Wu; Guangsuo Xing; Mengqi Chen; Zhihong Hao; Cheng Zhang; Jinye Zhang; Bochao Ma; Zihuang Liu; Hao Yuan; Zijian Liu; Qi Long; Yanshuang Zhou; Juntao Qi; Danyun Zhao; Mi Gao; Duanqing Pei; Jinfu Nie; Dan Ye; Guangjin Pan; Xingguo Liu

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-10-08
  • The cross-talk of energy sensing and mitochondrial anchoring sustains synaptic efficacy by maintaining presynaptic metabolism
    Nat. Metab. Pub Date : 2020-10-05
    Sunan Li; Gui-Jing Xiong; Ning Huang; Zu-Hang Sheng

    Mitochondria supply ATP essential for synaptic transmission. Neurons face exceptional challenges in maintaining energy homoeostasis at synapses. Regulation of mitochondrial trafficking and anchoring is critical for neurons to meet increased energy consumption during sustained synaptic activity. However, mechanisms recruiting and retaining presynaptic mitochondria in sensing synaptic ATP levels remain

    更新日期:2020-10-05
  • Diving deep—multipronged investigations into RIPK1 as a risk factor for obesity
    Nat. Metab. Pub Date : 2020-09-28
    Nicholas John Timpson

    A recent study by Karunakaran et al. suggests that RIPK1 is important in obesity and related metabolic traits. With genetic variation associated with expression and the risk of obesity, and repression of activity leading to a favourable metabolic profile in an obesogenic model, is there evidence for a potential therapeutic role?

    更新日期:2020-09-28
  • RIPK1 gene variants associate with obesity in humans and can be therapeutically silenced to reduce obesity in mice
    Nat. Metab. Pub Date : 2020-09-28
    Denuja Karunakaran; Adam W. Turner; Anne-Claire Duchez; Sebastien Soubeyrand; Adil Rasheed; David Smyth; David P. Cook; Majid Nikpay; Joshua W. Kandiah; Calvin Pan; Michele Geoffrion; Richard Lee; Ludovic Boytard; Hailey Wyatt; My-Anh Nguyen; Paulina Lau; Markku Laakso; Bhama Ramkhelawon; Marcus Alvarez; Kirsi H. Pietiläinen; Päivi Pajukanta; Barbara C. Vanderhyden; Peter Liu; Scott B. Berger; Peter

    Obesity is a major public health burden worldwide and is characterized by chronic low-grade inflammation driven by the cooperation of the innate immune system and dysregulated metabolism in adipose tissue and other metabolic organs. Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a central regulator of inflammatory cell function that coordinates inflammation, apoptosis and necroptosis

    更新日期:2020-09-28
  • Publisher Correction: The smell of death and deCYStiny: polyamines play the hero
    Nat. Metab. Pub Date : 2020-09-24
    Joseph A. Combs; Gina M. DeNicola

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-09-25
  • A large-scale genome-lipid association map guides lipid identification.
    Nat. Metab. Pub Date : 2020-09-21
    Vanessa Linke,Katherine A Overmyer,Ian J Miller,Dain R Brademan,Paul D Hutchins,Edna A Trujillo,Thiru R Reddy,Jason D Russell,Emily M Cushing,Kathryn L Schueler,Donald S Stapleton,Mary E Rabaglia,Mark P Keller,Daniel M Gatti,Gregory R Keele,Duy Pham,Karl W Broman,Gary A Churchill,Alan D Attie,Joshua J Coon

    Despite the crucial roles of lipids in metabolism, we are still at the early stages of comprehensively annotating lipid species and their genetic basis. Mass spectrometry–based discovery lipidomics offers the potential to globally survey lipids and their relative abundances in various biological samples. To discover the genetics of lipid features obtained through high-resolution liquid chromatography–tandem

    更新日期:2020-09-21
  • Metabolic and epigenetic regulation of T-cell exhaustion.
    Nat. Metab. Pub Date : 2020-09-21
    Fabien Franco,Alison Jaccard,Pedro Romero,Yi-Ru Yu,Ping-Chih Ho

    Current immunotherapies yield remarkable clinical outcomes by boosting the power of host immunity in cancer cell elimination and viral clearance. However, after prolonged antigen exposure, CD8+ T cells differentiate into a special differentiation state known as T-cell exhaustion, which poses one of the major hurdles to antiviral and antitumor immunity during chronic viral infection and tumour development

    更新日期:2020-09-21
  • Stable human regulatory T cells switch to glycolysis following TNF receptor 2 costimulation.
    Nat. Metab. Pub Date : 2020-09-21
    Sander de Kivit,Mark Mensink,Anna T Hoekstra,Ilana Berlin,Rico J E Derks,Demi Both,Muhammad A Aslam,Derk Amsen,Celia R Berkers,Jannie Borst

    Following activation, conventional T (Tconv) cells undergo an mTOR-driven glycolytic switch. Regulatory T (Treg) cells reportedly repress the mTOR pathway and avoid glycolysis. However, here we demonstrate that human thymus-derived Treg (tTreg) cells can become glycolytic in response to tumour necrosis factor receptor 2 (TNFR2) costimulation. This costimulus increases proliferation and induces a glycolytic

    更新日期:2020-09-21
  • 2020: a year of loss and delays.
    Nat. Metab. Pub Date : 2020-09-17

    As the world came to a standstill in the spring of 2020, so did the work on our Focus issue on exercise metabolism and health, which was originally scheduled for publication to coincide with the 2020 Summer Olympic Games.

    更新日期:2020-09-18
  • World-class athletic performance and genetic endowment.
    Nat. Metab. Pub Date : 2020-09-17
    Mark A Sarzynski,Claude Bouchard

    Individual differences in physical performance in the sedentary state and in response to exercise training have been observed in rodent and human studies. The genomic variants underlying these genetic components are unknown. Nonetheless, without a rich genetic endowment, world-class athletic performance is out of reach.

    更新日期:2020-09-18
  • Fgr kinase is required for proinflammatory macrophage activation during diet-induced obesity.
    Nat. Metab. Pub Date : 2020-09-17
    Rebeca Acín-Pérez,Salvador Iborra,Yolanda Martí-Mateos,Emma C L Cook,Ruth Conde-Garrosa,Anton Petcherski,Mª Del Mar Muñoz,Raquel Martínez de Mena,Karthickeyan Chella Krishnan,Concepción Jiménez,Juan Pedro Bolaños,Markku Laakso,Aldon J Lusis,Orian S Shirihai,David Sancho,José Antonio Enríquez

    Proinflammatory macrophages are key in the development of obesity. In addition, reactive oxygen species (ROS), which activate the Fgr tyrosine kinase, also contribute to obesity. Here we show that ablation of Fgr impairs proinflammatory macrophage polarization while preventing high-fat diet (HFD)-induced obesity in mice. Systemic ablation of Fgr increases lipolysis and liver fatty acid oxidation, thereby

    更新日期:2020-09-18
  • The mega-importance of de novo lipogenesis in platelet production.
    Nat. Metab. Pub Date : 2020-09-14
    Ishac Nazy,Donald M Arnold,Gregory R Steinberg

    Aberrant upregulation of de novo lipogenesis is linked to non-alcoholic fatty liver disease and some cancers. A new study by Kelly et al. finds that inhibiting this pathway by blocking the activity of acetyl-CoA carboxylase has unexpected effects on the formation of platelets from megakaryocytes within the bone marrow of primates but not rodents, thus suggesting clinical implications for de novo lipogenesis

    更新日期:2020-09-14
  • Exercise and immunometabolic regulation in cancer.
    Nat. Metab. Pub Date : 2020-09-14
    Graeme J Koelwyn,Xueqian Zhuang,Tuomas Tammela,Andrea Schietinger,Lee W Jones

    Unhealthful lifestyle factors, such as obesity, disrupt organismal homeostasis and accelerate cancer pathogenesis, partly through metabolic and immunological dysregulation. Exercise is a prototypical strategy that maintains and restores homeostasis at the organismal, tissue, cellular and molecular levels and can prevent or inhibit numerous disease conditions, including cancer. Here, we review unhealthful

    更新日期:2020-09-14
  • De novo lipogenesis is essential for platelet production in humans.
    Nat. Metab. Pub Date : 2020-09-14
    Kenneth L Kelly,William J Reagan,Gabriele E Sonnenberg,Michelle Clasquin,Katherine Hales,Shoh Asano,Paul A Amor,Santos Carvajal-Gonzalez,Norimitsu Shirai,Marcy D Matthews,Kelvin W Li,Marc K Hellerstein,Nicholas B Vera,Trenton T Ross,Gregg Cappon,Arthur Bergman,Clare Buckeridge,Zhongyuan Sun,Enida Ziso Qejvanaj,Theodore Schmahai,David Beebe,Jeffrey A Pfefferkorn,William P Esler

    Acetyl-CoA carboxylase (ACC) catalyses the first step of de novo lipogenesis (DNL). Pharmacologic inhibition of ACC has been of interest for therapeutic intervention in a wide range of diseases. We demonstrate here that ACC and DNL are essential for platelet production in humans and monkeys, but in not rodents or dogs. During clinical evaluation of a systemically distributed ACC inhibitor, unexpected

    更新日期:2020-09-14
  • Effects of maternal and paternal exercise on offspring metabolism.
    Nat. Metab. Pub Date : 2020-09-14
    Joji Kusuyama,Ana Barbara Alves-Wagner,Nathan S Makarewicz,Laurie J Goodyear

    Maternal and paternal obesity and type 2 diabetes are recognized risk factors for the development of metabolic dysfunction in offspring, even when the offspring follow a healthful lifestyle. Multiple studies have demonstrated that regular physical activity in mothers and fathers has striking beneficial effects on offspring health, including preventing the development of metabolic disease in rodent

    更新日期:2020-09-14
  • Author Correction: Skeletal muscle energy metabolism during exercise.
    Nat. Metab. Pub Date : 2020-09-10
    Mark Hargreaves,Lawrence L Spriet

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-09-11
  • Author Correction: High-protein diets increase cardiovascular risk by activating macrophage mTOR to suppress mitophagy.
    Nat. Metab. Pub Date : 2020-09-09
    Xiangyu Zhang,Ismail Sergin,Trent D Evans,Se-Jin Jeong,Astrid Rodriguez-Velez,Divya Kapoor,Sunny Chen,Eric Song,Karyn B Holloway,Jan R Crowley,Slava Epelman,Conrad C Weihl,Abhinav Diwan,Daping Fan,Bettina Mittendorfer,Nathan O Stitziel,Joel D Schilling,Irfan J Lodhi,Babak Razani

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-09-10
  • I've got you under my skin.
    Nat. Metab. Pub Date : 2020-09-07
    Thierry Berney,Ekaterine Berishvili

    Islet of Langerhans transplantation as a cell therapy for type 1 diabetes faces obstacles that have prevented full and lasting engraftment in the liver, the currently preferred implantation site in clinical practice. Yu and colleagues circumvent these issues and achieve stable diabetes reversal by transplanting islets encapsulated in a simple collagen-based matrix into the more accessible subcutaneous

    更新日期:2020-09-08
  • Three-dimensional facial-image analysis to predict heterogeneity of the human ageing rate and the impact of lifestyle.
    Nat. Metab. Pub Date : 2020-09-07
    Xian Xia,Xingwei Chen,Gang Wu,Fang Li,Yiyang Wang,Yang Chen,Mingxu Chen,Xinyu Wang,Weiyang Chen,Bo Xian,Weizhong Chen,Yaqiang Cao,Chi Xu,Wenxuan Gong,Guoyu Chen,Donghong Cai,Wenxin Wei,Yizhen Yan,Kangping Liu,Nan Qiao,Xiaohui Zhao,Jin Jia,Wei Wang,Brian K Kennedy,Kang Zhang,Carlo V Cannistraci,Yong Zhou,Jing-Dong J Han

    Not all individuals age at the same rate. Methods such as the ‘methylation clock’ are invasive, rely on expensive assays of tissue samples and infer the ageing rate by training on chronological age, which is used as a reference for prediction errors. Here, we develop models based on convoluted neural networks through training on non-invasive three-dimensional (3D) facial images of approximately 5,000

    更新日期:2020-09-08
  • Hypothalamic perineuronal net assembly is required for sustained diabetes remission induced by fibroblast growth factor 1 in rats.
    Nat. Metab. Pub Date : 2020-09-07
    Kimberly M Alonge,Zaman Mirzadeh,Jarrad M Scarlett,Aric F Logsdon,Jenny M Brown,Elaine Cabrales,Christina K Chan,Karl J Kaiyala,Marie A Bentsen,William A Banks,Miklos Guttman,Thomas N Wight,Gregory J Morton,Michael W Schwartz

    We recently showed that perineuronal nets (PNNs) enmesh glucoregulatory neurons in the arcuate nucleus (Arc) of the mediobasal hypothalamus (MBH)1, but whether these PNNs play a role in either the pathogenesis of type 2 diabetes (T2D) or its treatment remains unclear. Here we show that PNN abundance within the Arc is markedly reduced in the Zucker diabetic fatty (ZDF) rat model of T2D, compared with

    更新日期:2020-09-08
  • Islet transplantation in the subcutaneous space achieves long-term euglycaemia in preclinical models of type 1 diabetes.
    Nat. Metab. Pub Date : 2020-09-07
    Ming Yu,Divyansh Agarwal,Laxminarayana Korutla,Catherine L May,Wei Wang,Negin Noorchashm Griffith,Bernhard J Hering,Klaus H Kaestner,Omaida C Velazquez,James F Markmann,Prashanth Vallabhajosyula,Chengyang Liu,Ali Naji

    The intrahepatic milieu is inhospitable to intraportal islet allografts1,2,3, limiting their applicability for the treatment of type 1 diabetes. Although the subcutaneous space represents an alternate, safe and easily accessible site for pancreatic islet transplantation, lack of neovascularization and the resulting hypoxic cell death have largely limited the longevity of graft survival and function

    更新日期:2020-09-08
  • Autoantibody-negative insulin-dependent diabetes mellitus after SARS-CoV-2 infection: a case report.
    Nat. Metab. Pub Date : 2020-09-02
    Tim Hollstein,Dominik M Schulte,Juliane Schulz,Andreas Glück,Anette G Ziegler,Ezio Bonifacio,Mareike Wendorff,Andre Franke,Stefan Schreiber,Stefan R Bornstein,Matthias Laudes

    Here we report a case where the manifestations of insulin-dependent diabetes occurred following SARS-CoV-2 infection in a young individual in the absence of autoantibodies typical for type 1 diabetes mellitus. Specifically, a 19-year-old white male presented at our emergency department with diabetic ketoacidosis, C-peptide level of 0.62 µg l–1, blood glucose concentration of 30.6 mmol l–1 (552 mg dl–1)

    更新日期:2020-09-02
  • Author Correction: Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality.
    Nat. Metab. Pub Date : 2020-09-01
    David Legouis,Sven-Erick Ricksten,Anna Faivre,Thomas Verissimo,Karim Gariani,Charles Verney,Pierre Galichon,Lena Berchtold,Eric Feraille,Marylise Fernandez,Sandrine Placier,Kari Koppitch,Alexandre Hertig,Pierre-Yves Martin,Maarten Naesens,Jérôme Pugin,Andrew P McMahon,Pietro E Cippà,Sophie de Seigneux

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-09-01
  • Cellular metabolic reprogramming controls sugar appetite in Drosophila.
    Nat. Metab. Pub Date : 2020-08-31
    Zita Carvalho-Santos,Rita Cardoso-Figueiredo,Ana Paula Elias,Ibrahim Tastekin,Célia Baltazar,Carlos Ribeiro

    Cellular metabolic reprogramming is an important mechanism by which cells rewire their metabolism to promote proliferation and cell growth. This process has been mostly studied in the context of tumorigenesis, but less is known about its relevance for nonpathological processes and how it affects whole-animal physiology. Here, we show that metabolic reprogramming in Drosophila female germline cells

    更新日期:2020-08-31
  • Fructose stimulated de novo lipogenesis is promoted by inflammation.
    Nat. Metab. Pub Date : 2020-08-24
    Jelena Todoric,Giuseppe Di Caro,Saskia Reibe,Darren C Henstridge,Courtney R Green,Alison Vrbanac,Fatih Ceteci,Claire Conche,Reginald McNulty,Shabnam Shalapour,Koji Taniguchi,Peter J Meikle,Jeramie D Watrous,Rafael Moranchel,Mahan Najhawan,Mohit Jain,Xiao Liu,Tatiana Kisseleva,Maria T Diaz-Meco,Jorge Moscat,Rob Knight,Florian R Greten,Lester F Lau,Christian M Metallo,Mark A Febbraio,Michael Karin

    Benign hepatosteatosis, affected by lipid uptake, de novo lipogenesis and fatty acid (FA) oxidation, progresses to non-alcoholic steatohepatitis (NASH) on stress and inflammation. A key macronutrient proposed to increase hepatosteatosis and NASH risk is fructose. Excessive intake of fructose causes intestinal-barrier deterioration and endotoxaemia. However, how fructose triggers these alterations and

    更新日期:2020-08-24
  • Glis1 facilitates induction of pluripotency via an epigenome-metabolome-epigenome signalling cascade.
    Nat. Metab. Pub Date : 2020-08-24
    Linpeng Li,Keshi Chen,Tianyu Wang,Yi Wu,Guangsuo Xing,Mengqi Chen,Zhihong Hao,Cheng Zhang,Jinye Zhang,Bochao Ma,Zihuang Liu,Hao Yuan,Zijian Liu,Qi Long,Yanshuang Zhou,Juntao Qi,Danyun Zhao,Mi Gao,Duanqing Pei,Jinfu Nie,Dan Ye,Guangjin Pan,Xingguo Liu

    Somatic cell reprogramming provides insight into basic principles of cell fate determination, which remain poorly understood. Here we show that the transcription factor Glis1 induces multi-level epigenetic and metabolic remodelling in stem cells that facilitates the induction of pluripotency. We find that Glis1 enables reprogramming of senescent cells into pluripotent cells and improves genome stability

    更新日期:2020-08-24
  • Exercise and cardiac health: physiological and molecular insights.
    Nat. Metab. Pub Date : 2020-08-17
    Jose B N Moreira,Martin Wohlwend,Ulrik Wisløff

    The cardiac benefits of exercise have been recognized for centuries. Studies have undisputedly shown that regular exercise is beneficial for the cardiovascular system in young, old, healthy and diseased populations. For these reasons, physical activity has been recommended worldwide for cardiovascular disease prevention and treatment. Although the benefits of exercise are clear, understanding of the

    更新日期:2020-08-17
  • Author Correction: Defects in mtDNA replication challenge nuclear genome stability through nucleotide depletion and provide a unifying mechanism for mouse progerias.
    Nat. Metab. Pub Date : 2020-08-10
    Riikka H Hämäläinen,Juan C Landoni,Kati J Ahlqvist,Steffi Goffart,Sanna Ryytty,M Obaidur Rahman,Virginia Brilhante,Katherine Icay,Sampsa Hautaniemi,Liya Wang,Marikki Laiho,Anu Suomalainen

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-08-10
  • AMPK controls the axonal regenerative ability of dorsal root ganglia sensory neurons after spinal cord injury.
    Nat. Metab. Pub Date : 2020-08-10
    Guiping Kong,Luming Zhou,Elisabeth Serger,Ilaria Palmisano,Francesco De Virgiliis,Thomas H Hutson,Eilidh Mclachlan,Anja Freiwald,Paolo La Montanara,Kirill Shkura,Radhika Puttagunta,Simone Di Giovanni

    Regeneration after injury occurs in axons that lie in the peripheral nervous system but fails in the central nervous system, thereby limiting functional recovery. Differences in axonal signalling in response to injury that might underpin this differential regenerative ability are poorly characterized. Combining axoplasmic proteomics from peripheral sciatic or central projecting dorsal root ganglion

    更新日期:2020-08-10
  • Proofreading deficiency in mitochondrial DNA polymerase does not affect total dNTP pools in mouse embryos.
    Nat. Metab. Pub Date : 2020-08-10
    Sushma Sharma,Camilla Koolmeister,Phong Tran,Anna Karin Nilsson,Nils-Göran Larsson,Andrei Chabes

    更新日期:2020-08-10
  • Reply to: Proofreading deficiency in mitochondrial DNA polymerase does not affect total dNTP pools in mouse embryos.
    Nat. Metab. Pub Date : 2020-08-10
    Riikka H Hämäläinen,Juan C Landoni,Kati J Ahlqvist,Steffi Goffart,Sanna Ryytty,M Obaidur Rahman,Virginia Brilhante,Katherine Icay,Sampsa Hautaniemi,Liya Wang,Marikki Laiho,Anu Suomalainen

    更新日期:2020-08-10
  • Career pathways, part 2.
    Nat. Metab. Pub Date : 2020-08-07
    Myriam Aouadi,Anja Zeigerer

    In this instalment of Career pathways, we hear from Anja Zeigerer and Myriam Aouadi about how the support of institutions, labs and families can galvanize scientists’ passion and productivity.

    更新日期:2020-08-08
  • The smell of death and deCYStiny: polyamines play the hero.
    Nat. Metab. Pub Date : 2020-08-03
    Joseph A Combs,Gina M DeNicola

    Cancer cells require exogenous cysteine for proliferation and survival. In this issue of Nature Metabolism, Zhang et al. demonstrate that deletion of 5-methylthioadenosine phosphorylase promotes the synthesis of polyamines from methionine, thereby conferring sensitivity to cysteine starvation.

    更新日期:2020-08-03
  • Polyamine pathway activity promotes cysteine essentiality in cancer cells.
    Nat. Metab. Pub Date : 2020-08-03
    Tong Zhang,Christin Bauer,Alice C Newman,Alejandro Huerta Uribe,Dimitris Athineos,Karen Blyth,Oliver D K Maddocks

    Cancer cells have high demands for non-essential amino acids (NEAAs), which are precursors for anabolic and antioxidant pathways that support cell survival and proliferation. It is well-established that cancer cells consume the NEAA cysteine, and that cysteine deprivation can induce cell death; however, the specific factors governing acute sensitivity to cysteine starvation are poorly characterized

    更新日期:2020-08-03
  • Metabolic communication during exercise.
    Nat. Metab. Pub Date : 2020-08-03
    Robyn M Murphy,Matthew J Watt,Mark A Febbraio

    The coordination of nutrient sensing, delivery, uptake and utilization is essential for maintaining cellular, tissue and whole-body homeostasis. Such synchronization can be achieved only if metabolic information is communicated between the cells and tissues of the entire organism. During intense exercise, the metabolic demand of the body can increase approximately 100-fold. Thus, exercise is a physiological

    更新日期:2020-08-03
  • Skeletal muscle energy metabolism during exercise.
    Nat. Metab. Pub Date : 2020-08-03
    Mark Hargreaves,Lawrence L Spriet

    The continual supply of ATP to the fundamental cellular processes that underpin skeletal muscle contraction during exercise is essential for sports performance in events lasting seconds to several hours. Because the muscle stores of ATP are small, metabolic pathways must be activated to maintain the required rates of ATP resynthesis. These pathways include phosphocreatine and muscle glycogen breakdown

    更新日期:2020-08-03
  • Metabolic conditioning of CD8+ effector T cells for adoptive cell therapy.
    Nat. Metab. Pub Date : 2020-08-03
    Ramon I Klein Geltink,Joy Edwards-Hicks,Petya Apostolova,David O'Sullivan,David E Sanin,Annette E Patterson,Daniel J Puleston,Nina A M Ligthart,Joerg M Buescher,Katarzyna M Grzes,Agnieszka M Kabat,Michal Stanczak,Jonathan D Curtis,Fabian Hässler,Franziska M Uhl,Mario Fabri,Robert Zeiser,Edward J Pearce,Erika L Pearce

    CD8+ effector T (TE) cell proliferation and cytokine production depends on enhanced glucose metabolism. However, circulating T cells continuously adapt to glucose fluctuations caused by diet and inter-organ metabolite exchange. Here we show that transient glucose restriction (TGR) in activated CD8+ TE cells metabolically primes effector functions and enhances tumour clearance in mice. Tumour-specific

    更新日期:2020-08-03
  • A spoonful of DHAP keeps mTORC1 running on sugars.
    Nat. Metab. Pub Date : 2020-07-27
    Gerta Hoxhaj,Jason W Locasale,Issam Ben-Sahra

    The mechanistic target of rapamycin complex 1 (mTORC1) network integrates nutrient and energy signals that regulate metabolism and cell growth. Orozco et al. now show that the glycolytic intermediate dihydroxyacetone phosphate (DHAP) relays glycolytic activity to mTORC1 signalling.

    更新日期:2020-07-27
  • Seeing the forest for the trees in obesity.
    Nat. Metab. Pub Date : 2020-07-27
    Scott M Sternson

    GABA-expressing neurons in the arcuate nucleus of the hypothalamus regulate obesity in mice. A recent study indicates the importance of unexamined cell types.

    更新日期:2020-07-27
  • AMPK as a direct sensor of long-chain fatty acyl-CoA esters.
    Nat. Metab. Pub Date : 2020-07-27
    D Grahame Hardie

    AMPK is a crucial sensor of the cellular energetic state and is also activated during glucose starvation. A new study reports that AMP-activated protein kinase (AMPK) is activated by interaction with long-chain fatty acyl–CoA esters, which appear to be the long-sought endogenous AMPK ligands that bind the allosteric drug and metabolite (ADaM) site.

    更新日期:2020-07-27
  • Dihydroxyacetone phosphate signals glucose availability to mTORC1.
    Nat. Metab. Pub Date : 2020-07-27
    Jose M Orozco,Patrycja A Krawczyk,Sonia M Scaria,Andrew L Cangelosi,Sze Ham Chan,Tenzin Kunchok,Caroline A Lewis,David M Sabatini

    The mechanistic target of rapamycin complex 1 (mTORC1) kinase regulates cell growth by setting the balance between anabolic and catabolic processes. To be active, mTORC1 requires the environmental presence of amino acids and glucose. While a mechanistic understanding of amino acid sensing by mTORC1 is emerging, how glucose activates mTORC1 remains mysterious. Here, we used metabolically engineered

    更新日期:2020-07-27
  • Long-chain fatty acyl-CoA esters regulate metabolism via allosteric control of AMPK β1 isoforms.
    Nat. Metab. Pub Date : 2020-07-27
    Stephen L Pinkosky,John W Scott,Eric M Desjardins,Brennan K Smith,Emily A Day,Rebecca J Ford,Christopher G Langendorf,Naomi X Y Ling,Tracy L Nero,Kim Loh,Sandra Galic,Ashfaqul Hoque,William J Smiles,Kevin R W Ngoei,Michael W Parker,Yan Yan,Karsten Melcher,Bruce E Kemp,Jonathan S Oakhill,Gregory R Steinberg

    Long-chain fatty acids (LCFAs) play important roles in cellular energy metabolism, acting as both an important energy source and signalling molecules1. LCFA-CoA esters promote their own oxidation by acting as allosteric inhibitors of acetyl-CoA carboxylase, which reduces the production of malonyl-CoA and relieves inhibition of carnitine palmitoyl-transferase 1, thereby promoting LCFA-CoA transport

    更新日期:2020-07-27
  • Profound and redundant functions of arcuate neurons in obesity development.
    Nat. Metab. Pub Date : 2020-07-27
    Canjun Zhu,Zhiying Jiang,Yuanzhong Xu,Zhao-Lin Cai,Qingyan Jiang,Yong Xu,Mingshan Xue,Benjamin R Arenkiel,Qi Wu,Gang Shu,Qingchun Tong

    The current obesity epidemic faces a lack of mechanistic insights. It is known that the acute activity changes of a growing number of brain neurons rapidly alter feeding behaviour; however, how these changes translate to obesity development and the fundamental mechanism underlying brain neurons in controlling body weight remain elusive. Here, we show that chronic activation of hypothalamic arcuate

    更新日期:2020-07-27
  • Genetics of extreme human longevity to guide drug discovery for healthy ageing.
    Nat. Metab. Pub Date : 2020-07-27
    Zhengdong D Zhang,Sofiya Milman,Jhih-Rong Lin,Shayne Wierbowski,Haiyuan Yu,Nir Barzilai,Vera Gorbunova,Warren C Ladiges,Laura J Niedernhofer,Yousin Suh,Paul D Robbins,Jan Vijg

    Ageing is the greatest risk factor for most common chronic human diseases, and it therefore is a logical target for developing interventions to prevent, mitigate or reverse multiple age-related morbidities. Over the past two decades, genetic and pharmacologic interventions targeting conserved pathways of growth and metabolism have consistently led to substantial extension of the lifespan and healthspan

    更新日期:2020-07-27
  • Genome-scale in vivo CRISPR screen identifies RNLS as a target for beta cell protection in type 1 diabetes.
    Nat. Metab. Pub Date : 2020-07-27
    Erica P Cai,Yuki Ishikawa,Wei Zhang,Nayara C Leite,Jian Li,Shurong Hou,Badr Kiaf,Jennifer Hollister-Lock,Nese Kurt Yilmaz,Celia A Schiffer,Douglas A Melton,Stephan Kissler,Peng Yi

    Type 1 diabetes (T1D) is caused by the autoimmune destruction of pancreatic beta cells. Pluripotent stem cells can now be differentiated into beta cells, thus raising the prospect of a cell replacement therapy for T1D. However, autoimmunity would rapidly destroy newly transplanted beta cells. Using a genome-scale CRISPR screen in a mouse model for T1D, we show that deleting RNLS, a genome-wide association

    更新日期:2020-07-27
  • Sugar not so sweet for training-enhanced fitness.
    Nat. Metab. Pub Date : 2020-07-20
    Katja A Lamia

    Diet and exercise are the two pillars of a healthful lifestyle for stemming the rising tide of metabolic disease. A new study in this issue reveals that the health benefits of diet and aerobic exercise are more interdependent than previously appreciated, thus reinforcing the importance of a holistic approach to maintaining a healthful lifestyle.

    更新日期:2020-07-20
  • Hyperglycaemia is associated with impaired muscle signalling and aerobic adaptation to exercise.
    Nat. Metab. Pub Date : 2020-07-20
    Tara L MacDonald,Pattarawan Pattamaprapanont,Prerana Pathak,Natalie Fernandez,Ellen C Freitas,Samar Hafida,Joanna Mitri,Steven L Britton,Lauren G Koch,Sarah J Lessard

    Increased aerobic exercise capacity, as a result of exercise training, has important health benefits. However, some individuals are resistant to improvements in exercise capacity, probably due to undetermined genetic and environmental factors. Here, we show that exercise-induced improvements in aerobic capacity are blunted and aerobic remodelling of skeletal muscle is impaired in several animal models

    更新日期:2020-07-20
  • Lactate: the ugly duckling of energy metabolism.
    Nat. Metab. Pub Date : 2020-07-20
    Joshua D Rabinowitz,Sven Enerbäck

    Lactate, perhaps the best-known metabolic waste product, was first isolated from sour milk, in which it is produced by lactobacilli. Whereas microbes also generate other fermentation products, such as ethanol or acetone, lactate dominates in mammals. Lactate production increases when the demand for ATP and oxygen exceeds supply, as occurs during intense exercise and ischaemia. The build-up of lactate

    更新日期:2020-07-20
  • DNA methylation mediates development of HbA1c-associated complications in type 1 diabetes.
    Nat. Metab. Pub Date : 2020-07-20
    Zhuo Chen,Feng Miao,Barbara H Braffett,John M Lachin,Lingxiao Zhang,Xiwei Wu,Delnaz Roshandel,Melanie Carless,Xuejun Arthur Li,Joshua D Tompkins,John S Kaddis,Arthur D Riggs,Andrew D Paterson,,Rama Natarajan

    Metabolic memory, the persistent benefits of early glycaemic control on preventing and/or delaying the development of diabetic complications, has been observed in the Diabetes Control and Complications Trial (DCCT) and in the Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study, but the underlying mechanisms remain unclear. Here, we show the involvement of epigenetic DNA

    更新日期:2020-07-20
  • Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality.
    Nat. Metab. Pub Date : 2020-07-20
    David Legouis,Sven-Erick Ricksten,Anna Faivre,Thomas Verissimo,Karim Gariani,Charles Verney,Pierre Galichon,Lena Berchtold,Eric Feraille,Marylise Fernandez,Sandrine Placier,Kari Koppitch,Alexandre Hertig,Pierre-Yves Martin,Maarten Naesens,Jérôme Pugin,Andrew P McMahon,Pietro E Cippà,Sophie de Seigneux

    Acute kidney injury (AKI) is strongly associated with mortality, independently of its cause. The kidney contributes to up to 40% of systemic glucose production by gluconeogenesis during fasting and under stress conditions. Whether kidney gluconeogenesis is impaired during AKI and how this might influence systemic metabolism remain unknown. Here we show that glucose production and lactate clearance

    更新日期:2020-07-20
  • A 'fast'er way to treat breast cancer.
    Nat. Metab. Pub Date : 2020-07-15
    Marcus D Goncalves,Lewis C Cantley

    Caffa et al. report in Nature that hormone-receptor-positive breast cancer is sensitive to a form of ‘dietary augmentation therapy’ that implements periods of fasting, thus enhancing anti-cancer therapy.

    更新日期:2020-07-15
  • Author Correction: Meteorin-like facilitates skeletal muscle repair through a Stat3/IGF-1 mechanism.
    Nat. Metab. Pub Date : 2020-07-14
    Gurpreet S Baht,Akshay Bareja,David E Lee,Rajesh R Rao,Rong Huang,Janet L Huebner,David B Bartlett,Corey R Hart,Jason R Gibson,Ian R Lanza,Virginia B Kraus,Simon G Gregory,Bruce M Spiegelman,James P White

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-07-14
  • Metabolic reprogramming in polycystic kidney disease explained by super-enhancers and CDK7: new therapeutic targets?
    Nat. Metab. Pub Date : 2020-07-13
    Laura Cassina,Alessandra Boletta

    In this issue of Nature Metabolism, Mi and colleagues provide evidence that super-enhancers play a critical role in autosomal-dominant polycystic kidney disease (ADPKD) and show that CDK7 targeting provides a novel therapeutic option.

    更新日期:2020-07-13
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