{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:03:05Z","timestamp":1753869785479,"version":"3.41.2"},"reference-count":46,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2018,8,8]],"date-time":"2018-08-08T00:00:00Z","timestamp":1533686400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["443492\/2014\u20100"],"award-info":[{"award-number":["443492\/2014\u20100"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["09\/15354\u20107","10\/52191\u20106","11\/10783\u20107","12\/02270\u20102","2015\/19530\u20105"],"award-info":[{"award-number":["09\/15354\u20107","10\/52191\u20106","11\/10783\u20107","12\/02270\u20102","2015\/19530\u20105"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:sec><jats:title>Scope<\/jats:title><jats:p>To test whether myeloid cells <jats:italic>Tsc1<\/jats:italic> deletion and therefore constitutive activation of the nutrient sensor mTORC1 protects from high\u2010fat diet (HFD)\u2010induced obesity, glucose intolerance, and adipose tissue inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Mice with <jats:italic>Tsc1<\/jats:italic> deletion in myeloid cells (MTsc1KO) and littermate controls (MTsc1WT) were fed with HFD for 8 weeks and evaluated for body weight, glucose homeostasis, and adipose tissue inflammation. MTsc1KO mice were protected from HFD\u2010induced obesity and glucose intolerance. MTsc1KO, however, displayed, independently of the diet, abnormal behavior, episodes of intense movement, and muscle spasms followed by temporary paralysis. To investigate whether obesity protection was due to myeloid cells Tsc1 deletion, bone marrow was transplanted from MTsc1WT and MTsc1KO into irradiated C57BL6\/J mice. Mice transplanted with MTsc1KO bone marrow displayed reduced body weight gain, adiposity, and inflammation, and enhanced energy expenditure, glucose tolerance and adipose tissue M2 macrophage content upon HFD feeding, in the absence of abnormal behavior. In vitro, <jats:italic>Tsc1<\/jats:italic> deletion increased in a mTORC1\u2010dependent manner macrophage polarization to M2 profile and mRNA levels of fatty acid binding protein 4 and PPAR\u03b3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Constitutive mTORC1 activation in myeloid cells protects mice from HFD\u2010induced obesity, adipose tissue inflammation, and glucose intolerance by promoting macrophage polarization to M2 pro\u2010resolution profile and increasing energy expenditure.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.201800283","type":"journal-article","created":{"date-parts":[[2018,7,12]],"date-time":"2018-07-12T20:54:03Z","timestamp":1531428843000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Constitutive Activation of the Nutrient Sensor mTORC1 in Myeloid Cells Induced by Tsc1 Deletion Protects Mice from Diet\u2010Induced Obesity"],"prefix":"10.1002","volume":"62","author":[{"given":"Vivian A.","family":"Paschoal","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo 05508000 Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thiago","family":"Belchior","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo 05508000 Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariane T.","family":"Amano","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo 05508000 Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Burgos\u2010Silva","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo 05508000 Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert S.","family":"Peixoto","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo 05508000 Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana","family":"Magdalon","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo 05508000 Brazil"},{"name":"Israelita Albert Einstein Hospital  S\u00e3o Paulo 05652\u2010900 Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thayna S.","family":"Vieira","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo 05508000 Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maynara L.","family":"Andrade","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo 05508000 Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9078-2795","authenticated-orcid":false,"given":"Mayara F.","family":"Moreno","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo 05508000 Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Chimin","sequence":"additional","affiliation":[{"name":"Department of Physical Education Physical Education and Sports Center Londrina State University  Londrina 86051\u2010990 Parana Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niels O.","family":"C\u00e2mara","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo 05508000 Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William T.","family":"Festuccia","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo 05508000 Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,8,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21363"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200319451"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200319246"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02866"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0921"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2016.09.014"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.017"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.02.002"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.2.717"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.05.058"},{"key":"e_1_2_7_12_1","first-page":"e11612","volume":"5","author":"Covarrubias A. J.","year":"2016","journal-title":"Life"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12126"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-014-3350-5"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M074518"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2016.02.023"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3655"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12858-016-0069-6"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102187"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3834"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1159\/000430306"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.08.012"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201400914"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M900301200"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5.5.8504"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.267pe24"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00683.2013"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00821.2009"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1001-1138"},{"key":"e_1_2_7_30_1","first-page":"637","volume":"6","author":"Castoldi A.","year":"2015","journal-title":"Front Immunol."},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29881"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2017.01.005"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2011.168"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.04.006"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3709"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.06.011"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00249.2013"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3746"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2015.122"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05894"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2015.03.042"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.11.2748"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3901"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep14534"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.01.026"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.35"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201646437"}],"container-title":["Molecular Nutrition &amp; Food Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmnfr.201800283","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mnfr.201800283","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T09:16:41Z","timestamp":1694942201000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mnfr.201800283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,8]]},"references-count":46,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2018,9]]}},"alternative-id":["10.1002\/mnfr.201800283"],"URL":"https:\/\/doi.org\/10.1002\/mnfr.201800283","archive":["Portico"],"relation":{},"ISSN":["1613-4125","1613-4133"],"issn-type":[{"type":"print","value":"1613-4125"},{"type":"electronic","value":"1613-4133"}],"subject":[],"published":{"date-parts":[[2018,8,8]]},"assertion":[{"value":"2018-03-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1800283"}}