{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T10:13:09Z","timestamp":1787998389519,"version":"build-2784847793"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2017,9,5]],"date-time":"2017-09-05T00:00:00Z","timestamp":1504569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005156","name":"Alexander von Humboldt-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005156","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Helmholtz Alliance ICEMED-Imaging and Curing Environmental Metabolic Diseases"},{"name":"Helmholtz Alliance ICEMED-Imaging and Curing Environmental Metabolic Diseases"},{"name":"Helmholtz-Israel-Cooperation in Personalized Medicine"},{"name":"iMed Helmholtz Initiative for Personalized Medicine"},{"name":"Initiative and Networking Fund of the Helmholtz Association"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0183488","type":"journal-article","created":{"date-parts":[[2017,9,5]],"date-time":"2017-09-05T13:43:24Z","timestamp":1504619004000},"page":"e0183488","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["Dual specificity phosphatase 6 deficiency is associated with impaired systemic glucose tolerance and reversible weight retardation in mice"],"prefix":"10.1371","volume":"12","author":[{"given":"Katrin","family":"Pfuhlmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul T.","family":"Pfluger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja C.","family":"Schriever","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo D.","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias H.","family":"Tsch\u00f6p","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7526-2326","authenticated-orcid":true,"given":"Kerstin","family":"Stemmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2017,9,5]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/nrm715","article-title":"Mapk-regulated transcription: a continuously variable gene switch?","volume":"3","author":"CA Hazzalin","year":"2002","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1093\/jmcb\/mjq050","article-title":"ERK1 and ERK2 are involved in recruitment and maturation of human mesenchymal stem cells induced to adipogenic differentiation","volume":"3","author":"E Donzelli","year":"2011","journal-title":"J Mol Cell Biol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1042\/bj3610621","article-title":"Retinoic acid activation of the ERK pathway is required for embryonic stem cell commitment into the adipocyte lineage","volume":"361","author":"F Bost","year":"2002","journal-title":"Biochem J"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"402","DOI":"10.2337\/diabetes.54.2.402","article-title":"The extracellular signal-regulated kinase isoform ERK1 is specifically required for in vitro and in vivo adipogenesis","volume":"54","author":"F Bost","year":"2005","journal-title":"Diabetes"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"46226","DOI":"10.1074\/jbc.M207776200","article-title":"Activation of MEK\/ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor gamma (PPARgamma) and C\/EBPalpha gene expression during the differentiation of 3T3-L1 preadipocytes","volume":"277","author":"D Prusty","year":"2002","journal-title":"J Biol Chem"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"6068","DOI":"10.1128\/MCB.17.10.6068","article-title":"Mitogen-activated protein kinase activation is not necessary for, but antagonizes, 3T3-L1 adipocytic differentiation","volume":"17","author":"JF de Mora","year":"1997","journal-title":"Mol Cell Biol"},{"issue":"Pt 22","key":"ref7","doi-asserted-by":"crossref","first-page":"4607","DOI":"10.1242\/jcs.03266","article-title":"Diverse physiological functions for dual-specificity MAP kinase phosphatases","volume":"119","author":"R Dickinson","year":"2006","journal-title":"J Cell Sci"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.cmet.2009.09.010","article-title":"KSR2 is an essential regulator of AMP kinase, energy expenditure, and insulin sensitivity","volume":"10","author":"DL Costanzo-Garvey","year":"2009","journal-title":"Cell Metabolism"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"7592","DOI":"10.1128\/MCB.25.17.7592-7604.2005","article-title":"The molecular scaffold kinase suppressor of Ras 1 (KSR1) regulates adipogenesis","volume":"25","author":"RL Kortum","year":"2005","journal-title":"Mol Cell Biol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.molcel.2009.06.001","article-title":"KSR2 is a calcineurin substrate that promotes ERK cascade activation in response to calcium signals","volume":"34","author":"MK Dougherty","year":"2009","journal-title":"Mol Cell"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1128\/MCB.01359-08","article-title":"Ras subcellular localization defines extracellular signal-regulated kinase 1 and 2 substrate specificity through distinct utilization of scaffold proteins","volume":"29","author":"B Casar","year":"2009","journal-title":"Mol Cell Biol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.semcdb.2016.01.009","article-title":"The regulation of oncogenic Ras\/ERK signalling by dual-specificity mitogen activated protein kinase phosphatases (MKPs)","volume":"50","author":"AM Kidger","year":"2016","journal-title":"Semin Cell Dev Biol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1042\/BJ20082234","article-title":"Dual-specificity phosphatases: critical regulators with diverse cellular targets","volume":"418","author":"KI Patterson","year":"2009","journal-title":"Biochem J"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/nrd2289","article-title":"Targeting dual-specificity phosphatases: manipulating MAP kinase signalling and immune responses","volume":"6","author":"KL Jeffrey","year":"2007","journal-title":"Nat Rev Drug Discov"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"3621","DOI":"10.1002\/j.1460-2075.1996.tb00731.x","article-title":"Differential regulation of the MAP, SAP and RK\/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase","volume":"15","author":"LA Groom","year":"1996","journal-title":"EMBO J"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0925-4773(02)00153-3","article-title":"Cloning and expression of the mouse dual-specificity mitogen-activated protein (MAP) kinase phosphatase Mkp3 during mouse embryogenesis","volume":"116","author":"A Klock","year":"2002","journal-title":"Mech Dev"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"36013","DOI":"10.1074\/jbc.M508027200","article-title":"Dual specificity MAPK phosphatase 3 activates PEPCK gene transcription and increases gluconeogenesis in rat hepatoma cells","volume":"280","author":"H Xu","year":"2005","journal-title":"J Biol Chem"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1177\/0883073807313042","article-title":"Association of the dusp6 (mkp3) gene with mouse brain weight and forebrain structure","volume":"23","author":"B Liu","year":"2008","journal-title":"J Child Neurol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"31246","DOI":"10.1074\/jbc.M806085200","article-title":"DUSP6 (MKP3) null mice show enhanced ERK1\/2 phosphorylation at baseline and increased myocyte proliferation in the heart affecting disease susceptibility","volume":"283","author":"M Maillet","year":"2008","journal-title":"J Biol Chem"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"3052","DOI":"10.3892\/mmr.2014.2575","article-title":"Dual specificity phosphatase 6 suppresses the growth and metastasis of prostate cancer cells","volume":"10","author":"X Zhai","year":"2014","journal-title":"Mol Med Rep"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"3813","DOI":"10.1038\/onc.2011.99","article-title":"Dual-specificity phosphatase DUSP6 has tumor-promoting properties in human glioblastomas","volume":"30","author":"S Messina","year":"2011","journal-title":"Oncogene"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1093\/carcin\/bgn167","article-title":"Loss of MKP3 mediated by oxidative stress enhances tumorigenicity and chemoresistance of ovarian cancer cells","volume":"29","author":"DW Chan","year":"2008","journal-title":"Carcinogenesis"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.2337\/db14-0066","article-title":"Mitogen-activated protein kinase phosphatase 3 (MKP-3)-deficient mice are resistant to diet-induced obesity","volume":"63","author":"B Feng","year":"2014","journal-title":"Diabetes"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"3901","DOI":"10.1172\/JCI43250","article-title":"MAPK phosphatase-3 promotes hepatic gluconeogenesis through dephosphorylation of forkhead box O1 in mice","volume":"120","author":"Z Wu","year":"2010","journal-title":"J Clin Invest"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"e41168","DOI":"10.1371\/journal.pone.0041168","article-title":"Mapping MKP-3\/FOXO1 interaction and evaluating the effect on gluconeogenesis","volume":"7","author":"P Jiao","year":"2012","journal-title":"PLoS ONE"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.cmet.2015.08.022","article-title":"Calcineurin Links Mitochondrial Elongation with Energy Metabolism","volume":"22","author":"PT Pfluger","year":"2015","journal-title":"Cell Metabolism"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"3475","DOI":"10.1172\/JCI31743","article-title":"The central melanocortin system directly controls peripheral lipid metabolism","volume":"117","author":"R Nogueiras","year":"2007","journal-title":"J Clin Invest"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"27205","DOI":"10.1074\/jbc.271.44.27205","article-title":"The dual specificity phosphatases M3\/6 and MKP-3 are highly selective for inactivation of distinct mitogen-activated protein kinases","volume":"271","author":"M Muda","year":"1996","journal-title":"J Biol Chem"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"5875","DOI":"10.1074\/jbc.M410771200","article-title":"Reversible oxidation of ERK-directed protein phosphatases drives oxidative toxicity in neurons","volume":"280","author":"DJ Levinthal","year":"2005","journal-title":"J Biol Chem"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"11825","DOI":"10.1074\/jbc.M110.153049","article-title":"Dual-specific phosphatase-6 (Dusp6) and ERK mediate AMPA receptor-induced oligodendrocyte death","volume":"286","author":"M Domercq","year":"2011","journal-title":"Journal of Biological Chemistry"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.bbrc.2015.09.180","article-title":"Differential expression profiles and roles of inducible DUSPs and ERK1\/2-specific constitutive DUSP6 and DUSP7 in microglia","volume":"467","author":"J-E Ham","year":"2015","journal-title":"Biochem Biophys Res Commun"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"10993","DOI":"10.1073\/pnas.0503291102","article-title":"Aquaporin 7 deficiency is associated with development of obesity through activation of adipose glycerol kinase","volume":"102","author":"T Hibuse","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"5226","DOI":"10.1210\/en.2010-0496","article-title":"Ldlr \u2212\/\u2212Mice Display Decreased Susceptibility to Western-Type Diet-Induced Obesity Due to Increased Thermogenesis","volume":"151","author":"YF Ngai","year":"2010","journal-title":"Endocrinology"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"4796","DOI":"10.1111\/j.1742-4658.2008.06619.x","article-title":"Apolipoprotein E predisposes to obesity and related metabolic dysfunctions in mice","volume":"275","author":"I Karagiannides","year":"2008","journal-title":"FEBS J"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"E207","DOI":"10.1152\/ajpendo.2002.282.1.E207","article-title":"LDL receptor but not apolipoprotein E deficiency increases diet-induced obesity and diabetes in mice","volume":"282","author":"SA Schreyer","year":"2002","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1194\/jlr.M063354","article-title":"ABCG1 regulates mouse adipose tissue macrophage cholesterol levels and ratio of M1 to M2 cells in obesity and caloric restriction","volume":"56","author":"H Wei","year":"2015","journal-title":"J Lipid Res"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"840","DOI":"10.2337\/db14-0245","article-title":"Adipocyte ATP-Binding Cassette G1 Promotes Triglyceride Storage, Fat Mass Growth, and Human Obesity","volume":"64","author":"E Frisdal","year":"2015","journal-title":"Diabetes"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1194\/jlr.M200130-JLR200","article-title":"FATP1 channels exogenous FA into 1,2,3-triacyl-sn-glycerol and down-regulates sphingomyelin and cholesterol metabolism in growing 293 cells","volume":"43","author":"GM Hatch","year":"2002","journal-title":"J Lipid Res"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1172\/JCI200418917","article-title":"Inactivation of fatty acid transport protein 1 prevents fat-induced insulin resistance in skeletal muscle","volume":"113","author":"JK Kim","year":"2004","journal-title":"J Clin Invest"},{"key":"ref40","first-page":"1","article-title":"Dual-specificity phosphatase 6 deficiency regulates gut microbiome and transcriptome response against diet-induced obesity in mice","volume":"2","author":"J-W Ruan","year":"2016","journal-title":"Nat Microbiol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1007\/s00125-013-2846-8","article-title":"Mouse strain-dependent variation in obesity and glucose homeostasis in response to high-fat feeding","volume":"56","author":"MK Montgomery","year":"2013","journal-title":"Diabetologia"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1016\/j.celrep.2017.01.062","article-title":"Host Genotype and Gut Microbiome Modulate Insulin Secretion and Diet-Induced Metabolic Phenotypes","volume":"18","author":"JH Kreznar","year":"2017","journal-title":"Cell Reports"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"2960","DOI":"10.2337\/db10-0367","article-title":"A systems biology approach identifies inflammatory abnormalities between mouse strains prior to development of metabolic disease","volume":"59","author":"MA Mori","year":"2010","journal-title":"Diabetes"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1093\/femsre\/fuv036","article-title":"Heterogeneity of the gut microbiome in mice: guidelines for optimizing experimental design","volume":"40","author":"D Laukens","year":"2016","journal-title":"FEMS Microbiol Rev"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1084\/jem.20120504","article-title":"Familial transmission rather than defective innate immunity shapes the distinct intestinal microbiota of TLR-deficient mice","volume":"209","author":"C Ubeda","year":"2012","journal-title":"Journal of Experimental Medicine"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1126\/science.1179721","article-title":"Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5","volume":"328","author":"M Vijay-Kumar","year":"2010","journal-title":"Science"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1038\/ismej.2014.79","article-title":"Distinct signatures of host&amp;ndash;microbial meta-metabolome and gut microbiome in two C57BL&amp;sol;6 strains under high-fat diet","volume":"8","author":"A Walker","year":"2014","journal-title":"The ISME Journal"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"e0116704","DOI":"10.1371\/journal.pone.0116704","article-title":"Effects of vendor and genetic background on the composition of the fecal microbiota of inbred mice. Heimesaat MM, editor","volume":"10","author":"AC Ericsson","year":"2015","journal-title":"PLoS ONE"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"e8584","DOI":"10.1371\/journal.pone.0008584","article-title":"Site and strain-specific variation in gut microbiota profiles and metabolism in experimental mice","volume":"5","author":"MK Friswell","year":"2010","journal-title":"PLoS ONE"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s00248-010-9787-2","article-title":"Genotype is a stronger determinant than sex of the mouse gut microbiota","volume":"61","author":"A Kovacs","year":"2011","journal-title":"Microb Ecol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s00335-014-9540-0","article-title":"Responsiveness of cardiometabolic-related microbiota to diet is influenced by host genetics","volume":"25","author":"A O'Connor","year":"2014","journal-title":"Mamm Genome"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"R4","DOI":"10.1186\/gb-2013-14-1-r4","article-title":"Inflammation-associated enterotypes, host genotype, cage and inter-individual effects drive gut microbiota variation in common laboratory mice","volume":"14","author":"F Hildebrand","year":"2013","journal-title":"Genome Biol"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1113\/jphysiol.2013.264002","article-title":"Exercise training decreases mitogen-activated protein kinase phosphatase-3 expression and suppresses hepatic gluconeogenesis in obese mice","volume":"592","author":"LS Souza Pauli","year":"2014","journal-title":"J Physiol (Lond)"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.molmet.2016.07.004","article-title":"Interactions between host genetics and gut microbiome in diabetes and metabolic syndrome","volume":"5","author":"S Ussar","year":"2016","journal-title":"Mol Metab"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1073\/pnas.0605374104","article-title":"Mechanisms underlying the resistance to diet-induced obesity in germ-free mice","volume":"104","author":"F B\u00e4ckhed","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1017\/S0007114510001303","article-title":"Absence of intestinal microbiota does not protect mice from diet-induced obesity","volume":"104","author":"CK Fleissner","year":"2010","journal-title":"Br J Nutr"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0183488","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,10,3]],"date-time":"2019-10-03T00:42:58Z","timestamp":1570063378000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0183488"}},"subtitle":[],"editor":[{"given":"Ruben","family":"Nogueiras","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,9,5]]},"references-count":56,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2017,9,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0183488","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,5]]}}}