mTORC2 sustains thermogenesis via Akt-induced glucose uptake and glycolysis in brown adipose tissue.

Abstract:

:Activation of non-shivering thermogenesis (NST) in brown adipose tissue (BAT) has been proposed as an anti-obesity treatment. Moreover, cold-induced glucose uptake could normalize blood glucose levels in insulin-resistant patients. It is therefore important to identify novel regulators of NST and cold-induced glucose uptake. Mammalian target of rapamycin complex 2 (mTORC2) mediates insulin-stimulated glucose uptake in metabolic tissues, but its role in NST is unknown. We show that mTORC2 is activated in brown adipocytes upon β-adrenergic stimulation. Furthermore, mice lacking mTORC2 specifically in adipose tissue (AdRiKO mice) are hypothermic, display increased sensitivity to cold, and show impaired cold-induced glucose uptake and glycolysis. Restoration of glucose uptake in BAT by overexpression of hexokinase II or activated Akt2 was sufficient to increase body temperature and improve cold tolerance in AdRiKO mice. Thus, mTORC2 in BAT mediates temperature homeostasis via regulation of cold-induced glucose uptake. Our findings demonstrate the importance of glucose metabolism in temperature regulation.

journal_name

EMBO Mol Med

journal_title

EMBO molecular medicine

authors

Albert V,Svensson K,Shimobayashi M,Colombi M,Muñoz S,Jimenez V,Handschin C,Bosch F,Hall MN

doi

10.15252/emmm.201505610

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

232-46

issue

3

eissn

1757-4676

issn

1757-4684

pii

emmm.201505610

journal_volume

8

pub_type

杂志文章
  • Loss of the mitochondrial i-AAA protease YME1L leads to ocular dysfunction and spinal axonopathy.

    abstract::Disturbances in the morphology and function of mitochondria cause neurological diseases, which can affect the central and peripheral nervous system. The i-AAA protease YME1L ensures mitochondrial proteostasis and regulates mitochondrial dynamics by processing of the dynamin-like GTPase OPA1. Mutations in YME1L cause a...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201809288

    authors: Sprenger HG,Wani G,Hesseling A,König T,Patron M,MacVicar T,Ahola S,Wai T,Barth E,Rugarli EI,Bergami M,Langer T

    更新日期:2019-01-01 00:00:00

  • Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3.

    abstract::Nutrient availability is the major regulator of life and reproduction, and a complex cellular signaling network has evolved to adapt organisms to fasting. These sensor pathways monitor cellular energy metabolism, especially mitochondrial ATP production and NAD(+)/NADH ratio, as major signals for nutritional state. We ...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201403943

    authors: Khan NA,Auranen M,Paetau I,Pirinen E,Euro L,Forsström S,Pasila L,Velagapudi V,Carroll CJ,Auwerx J,Suomalainen A

    更新日期:2014-06-01 00:00:00

  • Simultaneous impairment of neuronal and metabolic function of mutated gephyrin in a patient with epileptic encephalopathy.

    abstract::Synaptic inhibition is essential for shaping the dynamics of neuronal networks, and aberrant inhibition plays an important role in neurological disorders. Gephyrin is a central player at inhibitory postsynapses, directly binds and organizes GABAA and glycine receptors (GABAARs and GlyRs), and is thereby indispensable ...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201505323

    authors: Dejanovic B,Djémié T,Grünewald N,Suls A,Kress V,Hetsch F,Craiu D,Zemel M,Gormley P,Lal D,EuroEPINOMICS Dravet working group.,Myers CT,Mefford HC,Palotie A,Helbig I,Meier JC,De Jonghe P,Weckhuysen S,Schwarz G

    更新日期:2015-12-01 00:00:00

  • A KDM6A-KLF10 reinforcing feedback mechanism aggravates diabetic podocyte dysfunction.

    abstract::Diabetic nephropathy is the leading cause of end-stage renal disease. Although dysfunction of podocytes, also termed glomerular visceral epithelial cells, is critically associated with diabetic nephropathy, the mechanism underlying podocyte dysfunction still remains obscure. Here, we identify that KDM6A, a histone lys...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201809828

    authors: Lin CL,Hsu YC,Huang YT,Shih YH,Wang CJ,Chiang WC,Chang PJ

    更新日期:2019-05-01 00:00:00

  • A surrogate marker for Abeta42 production in the CNS.

    abstract::Alzheimer's disease (AD) is the most common cause of dementia. There are currently no effective treatments that may delay the onset, slow the progression or prevent the disease. Unless such treatments are developed, the number of AD cases is expected to double in the next 30 years. There is overwhelming genetic and bi...

    journal_title:EMBO molecular medicine

    pub_type: 评论,杂志文章

    doi:10.1002/emmm.200900030

    authors: Holtzman DM

    更新日期:2009-07-01 00:00:00

  • A streptococcal lipid toxin induces membrane permeabilization and pyroptosis leading to fetal injury.

    abstract::Group B streptococci (GBS) are Gram-positive bacteria that cause infections in utero and in newborns. We recently showed that the GBS pigment is hemolytic and increased pigment production promotes bacterial penetration of human placenta. However, mechanisms utilized by the hemolytic pigment to induce host cell lysis a...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201404883

    authors: Whidbey C,Vornhagen J,Gendrin C,Boldenow E,Samson JM,Doering K,Ngo L,Ezekwe EA Jr,Gundlach JH,Elovitz MA,Liggitt D,Duncan JA,Adams Waldorf KM,Rajagopal L

    更新日期:2015-04-01 00:00:00

  • Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers.

    abstract::Germ-line mutations in the BRCA1 gene strongly predispose women to breast cancer (lifetime risk up to 80%). Furthermore, the BRCA1 protein is absent or present at very low levels in about one third of sporadic breast cancers. However, the mechanisms underlying BRCA1 somatic inactivation appear multiple and are still n...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201100136

    authors: Garcia AI,Buisson M,Bertrand P,Rimokh R,Rouleau E,Lopez BS,Lidereau R,Mikaélian I,Mazoyer S

    更新日期:2011-05-01 00:00:00

  • The cholesterol-binding protein NPC2 restrains recruitment of stromal macrophage-lineage cells to early-stage lung tumours.

    abstract::The tumour microenvironment is known to play an integral role in facilitating cancer progression at advanced stages, but its function in some pre-cancerous lesions remains elusive. We have used the (V600) (E)BRAF-driven mouse lung model that develop premalignant lesions to understand stroma-tumour interactions during ...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201404838

    authors: Kamata T,Jin H,Giblett S,Patel B,Patel F,Foster C,Pritchard C

    更新日期:2015-09-01 00:00:00

  • Sprouty2 loss-induced IL6 drives castration-resistant prostate cancer through scavenger receptor B1.

    abstract::Metastatic castration-resistant prostate cancer (mCRPC) is a lethal form of treatment-resistant prostate cancer and poses significant therapeutic challenges. Deregulated receptor tyrosine kinase (RTK) signalling mediated by loss of tumour suppressor Sprouty2 (SPRY2) is associated with treatment resistance. Using pre-c...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201708347

    authors: Patel R,Fleming J,Mui E,Loveridge C,Repiscak P,Blomme A,Harle V,Salji M,Ahmad I,Teo K,Hamdy FC,Hedley A,van den Broek N,Mackay G,Edwards J,Sansom OJ,Leung HY

    更新日期:2018-04-01 00:00:00

  • RGS5 promotes arterial growth during arteriogenesis.

    abstract::Arteriogenesis-the growth of collateral arterioles-partially compensates for the progressive occlusion of large conductance arteries as it may occur as a consequence of coronary, cerebral or peripheral artery disease. Despite being clinically highly relevant, mechanisms driving this process remain elusive. In this con...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201403864

    authors: Arnold C,Feldner A,Pfisterer L,Hödebeck M,Troidl K,Genové G,Wieland T,Hecker M,Korff T

    更新日期:2014-08-01 00:00:00

  • Spotlight on Mycobacteria and dendritic cells: will novel targets to fight tuberculosis emerge?

    abstract::Over thousands of years microbes and mammals have co-evolved, resulting in extraordinarily sophisticated molecular mechanisms permitting the organisms to survive together. Mycobacterium tuberculosis is one of the best examples of successful co-evolution, since the bacilli have infected one third of the human populatio...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1002/emmm.200900008

    authors: Mortellaro A,Robinson L,Ricciardi-Castagnoli P

    更新日期:2009-04-01 00:00:00

  • Modification of γ-secretase by nitrosative stress links neuronal ageing to sporadic Alzheimer's disease.

    abstract::Inherited familial Alzheimer's disease (AD) is characterized by small increases in the ratio of Aβ42 versus Aβ40 peptide which is thought to drive the amyloid plaque formation in the brain of these patients. Little is known however whether ageing, the major risk factor for sporadic AD, affects amyloid beta-peptide (Aβ...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201200243

    authors: Guix FX,Wahle T,Vennekens K,Snellinx A,Chávez-Gutiérrez L,Ill-Raga G,Ramos-Fernandez E,Guardia-Laguarta C,Lleó A,Arimon M,Berezovska O,Muñoz FJ,Dotti CG,De Strooper B

    更新日期:2012-07-01 00:00:00

  • A high-affinity, bivalent PDZ domain inhibitor complexes PICK1 to alleviate neuropathic pain.

    abstract::Maladaptive plasticity involving increased expression of AMPA-type glutamate receptors is involved in several pathologies, including neuropathic pain, but direct inhibition of AMPARs is associated with side effects. As an alternative, we developed a cell-permeable, high-affinity (~2 nM) peptide inhibitor, Tat-P4 -(C5)...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201911248

    authors: Christensen NR,De Luca M,Lever MB,Richner M,Hansen AB,Noes-Holt G,Jensen KL,Rathje M,Jensen DB,Erlendsson S,Bartling CR,Ammendrup-Johnsen I,Pedersen SE,Schönauer M,Nissen KB,Midtgaard SR,Teilum K,Arleth L,Sørensen AT

    更新日期:2020-06-08 00:00:00

  • Clarin-2 is essential for hearing by maintaining stereocilia integrity and function.

    abstract::Hearing relies on mechanically gated ion channels present in the actin-rich stereocilia bundles at the apical surface of cochlear hair cells. Our knowledge of the mechanisms underlying the formation and maintenance of the sound-receptive structure is limited. Utilizing a large-scale forward genetic screen in mice, gen...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201910288

    authors: Dunbar LA,Patni P,Aguilar C,Mburu P,Corns L,Wells HR,Delmaghani S,Parker A,Johnson S,Williams D,Esapa CT,Simon MM,Chessum L,Newton S,Dorning J,Jeyarajan P,Morse S,Lelli A,Codner GF,Peineau T,Gopal SR,Alagramam K

    更新日期:2019-09-01 00:00:00

  • The isolated carboxy-terminal domain of human mitochondrial leucyl-tRNA synthetase rescues the pathological phenotype of mitochondrial tRNA mutations in human cells.

    abstract::Mitochondrial (mt) diseases are multisystem disorders due to mutations in nuclear or mtDNA genes. Among the latter, more than 50% are located in transfer RNA (tRNA) genes and are responsible for a wide range of syndromes, for which no effective treatment is available at present. We show that three human mt aminoacyl-t...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201303198

    authors: Perli E,Giordano C,Pisano A,Montanari A,Campese AF,Reyes A,Ghezzi D,Nasca A,Tuppen HA,Orlandi M,Di Micco P,Poser E,Taylor RW,Colotti G,Francisci S,Morea V,Frontali L,Zeviani M,d'Amati G

    更新日期:2014-02-01 00:00:00

  • MYC and the unfolded protein response in cancer: synthetic lethal partners in crime?

    abstract::The transcription factors of the MYC family play pivotal roles in the initiation and progression of human cancers. High oncogenic level of MYC invades low-affinity sites and enhancer sequences, which subsequently alters the transcriptome, causes metabolic imbalance, and induces stress response. The endoplasmic reticul...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章,评审

    doi:10.15252/emmm.201911845

    authors: Zhang T,Li N,Sun C,Jin Y,Sheng X

    更新日期:2020-05-08 00:00:00

  • Selective targeting of neuroblastoma tumour-initiating cells by compounds identified in stem cell-based small molecule screens.

    abstract::Neuroblastoma (NB) is the most deadly extra-cranial solid tumour in children necessitating an urgent need for effective and less toxic treatments. One reason for the lack of efficacious treatments may be the inability of existing drugs to target the tumour-initiating or cancer stem cell population responsible for sust...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201000093

    authors: Smith KM,Datti A,Fujitani M,Grinshtein N,Zhang L,Morozova O,Blakely KM,Rotenberg SA,Hansford LM,Miller FD,Yeger H,Irwin MS,Moffat J,Marra MA,Baruchel S,Wrana JL,Kaplan DR

    更新日期:2010-09-01 00:00:00

  • DNA methylation profiling reveals a predominant immune component in breast cancers.

    abstract::Breast cancer is a molecularly, biologically and clinically heterogeneous group of disorders. Understanding this diversity is essential to improving diagnosis and optimizing treatment. Both genetic and acquired epigenetic abnormalities participate in cancer, but the involvement of the epigenome in breast cancer and it...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201100801

    authors: Dedeurwaerder S,Desmedt C,Calonne E,Singhal SK,Haibe-Kains B,Defrance M,Michiels S,Volkmar M,Deplus R,Luciani J,Lallemand F,Larsimont D,Toussaint J,Haussy S,Rothé F,Rouas G,Metzger O,Majjaj S,Saini K,Putmans P,Ham

    更新日期:2011-12-01 00:00:00

  • FGF21 gene therapy as treatment for obesity and insulin resistance.

    abstract::Prevalence of type 2 diabetes (T2D) and obesity is increasing worldwide. Currently available therapies are not suited for all patients in the heterogeneous obese/T2D population, hence the need for novel treatments. Fibroblast growth factor 21 (FGF21) is considered a promising therapeutic agent for T2D/obesity. Native ...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201708791

    authors: Jimenez V,Jambrina C,Casana E,Sacristan V,Muñoz S,Darriba S,Rodó J,Mallol C,Garcia M,León X,Marcó S,Ribera A,Elias I,Casellas A,Grass I,Elias G,Ferré T,Motas S,Franckhauser S,Mulero F,Navarro M,Haurigot V,Rube

    更新日期:2018-08-01 00:00:00

  • Antagonism of interferon signaling by fibroblast growth factors promotes viral replication.

    abstract::Fibroblast growth factors (FGFs) play key roles in the pathogenesis of different human diseases, but the cross-talk between FGFs and other cytokines remains largely unexplored. We identified an unexpected antagonistic effect of FGFs on the interferon (IFN) signaling pathway. Genetic or pharmacological inhibition of FG...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201911793

    authors: Maddaluno L,Urwyler C,Rauschendorfer T,Meyer M,Stefanova D,Spörri R,Wietecha M,Ferrarese L,Stoycheva D,Bender D,Li N,Strittmatter G,Nasirujjaman K,Beer HD,Staeheli P,Hildt E,Oxenius A,Werner S

    更新日期:2020-09-07 00:00:00

  • Pre-clinical validation of a selective anti-cancer stem cell therapy for Numb-deficient human breast cancers.

    abstract::The cell fate determinant Numb is frequently downregulated in human breast cancers (BCs), resulting in p53 inactivation and an aggressive disease course. In the mouse mammary gland, Numb/p53 downregulation leads to aberrant tissue morphogenesis, expansion of the stem cell compartment, and emergence of cancer stem cell...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201606940

    authors: Tosoni D,Pambianco S,Ekalle Soppo B,Zecchini S,Bertalot G,Pruneri G,Viale G,Di Fiore PP,Pece S

    更新日期:2017-05-01 00:00:00

  • A single epidermal stem cell strategy for safe ex vivo gene therapy.

    abstract::There is a widespread agreement from patient and professional organisations alike that the safety of stem cell therapeutics is of paramount importance, particularly for ex vivo autologous gene therapy. Yet current technology makes it difficult to thoroughly evaluate the behaviour of genetically corrected stem cells be...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201404353

    authors: Droz-Georget Lathion S,Rochat A,Knott G,Recchia A,Martinet D,Benmohammed S,Grasset N,Zaffalon A,Besuchet Schmutz N,Savioz-Dayer E,Beckmann JS,Rougemont J,Mavilio F,Barrandon Y

    更新日期:2015-04-01 00:00:00

  • Combined deletion of Pten and p53 in mammary epithelium accelerates triple-negative breast cancer with dependency on eEF2K.

    abstract::The tumor suppressors Pten and p53 are frequently lost in breast cancer, yet the consequences of their combined inactivation are poorly understood. Here, we show that mammary-specific deletion of Pten via WAP-Cre, which targets alveolar progenitors, induced tumors with shortened latency compared to those induced by MM...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201404402

    authors: Liu JC,Voisin V,Wang S,Wang DY,Jones RA,Datti A,Uehling D,Al-awar R,Egan SE,Bader GD,Tsao M,Mak TW,Zacksenhaus E

    更新日期:2014-12-01 00:00:00

  • A comparative evaluation of NB30, NB54 and PTC124 in translational read-through efficacy for treatment of an USH1C nonsense mutation.

    abstract::Translational read-through-inducing drugs (TRIDs) promote read-through of nonsense mutations, placing them in the spotlight of current gene-based therapeutic research. Here, we compare for the first time the relative efficacies of new-generation aminoglycosides NB30, NB54 and the chemical compound PTC124 on retinal to...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201201438

    authors: Goldmann T,Overlack N,Möller F,Belakhov V,van Wyk M,Baasov T,Wolfrum U,Nagel-Wolfrum K

    更新日期:2012-11-01 00:00:00

  • A transcriptional network underlies susceptibility to kidney disease progression.

    abstract::The molecular networks that control the progression of chronic kidney diseases (CKD) are poorly defined. We have recently shown that the susceptibility to development of renal lesions after nephron reduction is controlled by a locus on mouse chromosome 6 and requires epidermal growth factor receptor (EGFR) activation....

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201101127

    authors: Laouari D,Burtin M,Phelep A,Bienaime F,Noel LH,Lee DC,Legendre C,Friedlander G,Pontoglio M,Terzi F

    更新日期:2012-08-01 00:00:00

  • Molecular pathogenesis of spondylocheirodysplastic Ehlers-Danlos syndrome caused by mutant ZIP13 proteins.

    abstract::The zinc transporter protein ZIP13 plays critical roles in bone, tooth, and connective tissue development, and its dysfunction is responsible for the spondylocheirodysplastic form of Ehlers-Danlos syndrome (SCD-EDS, OMIM 612350). Here, we report the molecular pathogenic mechanism of SCD-EDS caused by two different mut...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201303809

    authors: Bin BH,Hojyo S,Hosaka T,Bhin J,Kano H,Miyai T,Ikeda M,Kimura-Someya T,Shirouzu M,Cho EG,Fukue K,Kambe T,Ohashi W,Kim KH,Seo J,Choi DH,Nam YJ,Hwang D,Fukunaka A,Fujitani Y,Yokoyama S,Superti-Furga A,Ikegawa S,

    更新日期:2014-08-01 00:00:00

  • Oral administration of pyrophosphate inhibits connective tissue calcification.

    abstract::Various disorders including pseudoxanthoma elasticum (PXE) and generalized arterial calcification of infancy (GACI), which are caused by inactivating mutations in ABCC6 and ENPP1, respectively, present with extensive tissue calcification due to reduced plasma pyrophosphate (PPi). However, it has always been assumed th...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201707532

    authors: Dedinszki D,Szeri F,Kozák E,Pomozi V,Tőkési N,Mezei TR,Merczel K,Letavernier E,Tang E,Le Saux O,Arányi T,van de Wetering K,Váradi A

    更新日期:2017-11-01 00:00:00

  • TREM2 deficiency reduces the efficacy of immunotherapeutic amyloid clearance.

    abstract::Immunotherapeutic approaches are currently the most advanced treatments for Alzheimer's disease (AD). Antibodies against amyloid β-peptide (Aβ) bind to amyloid plaques and induce their clearance by microglia via Fc receptor-mediated phagocytosis. Dysfunctions of microglia may play a pivotal role in AD pathogenesis and...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201606370

    authors: Xiang X,Werner G,Bohrmann B,Liesz A,Mazaheri F,Capell A,Feederle R,Knuesel I,Kleinberger G,Haass C

    更新日期:2016-09-01 00:00:00

  • Adeno-associated virus-vectored influenza vaccine elicits neutralizing and Fcγ receptor-activating antibodies.

    abstract::The current seasonal inactivated influenza vaccine protects only against a narrow range of virus strains as it triggers a dominant antibody response toward the hypervariable hemagglutinin (HA) head region. The discovery of rare broadly protective antibodies against conserved regions in influenza virus proteins has pro...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201910938

    authors: Demminger DE,Walz L,Dietert K,Hoffmann H,Planz O,Gruber AD,von Messling V,Wolff T

    更新日期:2020-05-08 00:00:00

  • iPhemap: an atlas of phenotype to genotype relationships of human iPSC models of neurological diseases.

    abstract::Disease modeling with induced pluripotent stem cells (iPSCs) is creating an abundance of phenotypic information that has become difficult to follow and interpret. Here, we report a systematic analysis of research practices and reporting bias in neurological disease models from 93 published articles. We find heterogene...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201708191

    authors: Hollingsworth EW,Vaughn JE,Orack JC,Skinner C,Khouri J,Lizarraga SB,Hester ME,Watanabe F,Kosik KS,Imitola J

    更新日期:2017-12-01 00:00:00