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In addition, metabolic diseases impact the architecture and function of mitochondria-ER contact sites (MERCs), changes which associate with mitofusin 2 (MFN2) repression in muscle, liver and hypothalamic neurons. MFN2 is a potent modulator of mitochondrial metabolism and insulin signaling, with a key role in mitochondrial dynamics and tethering with the ER. Here, we investigated whether offspring born to mice with MFN2-deficient oocytes are prone to obesity and diabetes. Deletion of Mfn2 in oocytes resulted in a profound transcriptomic change, with evidence of impaired mitochondrial and ER function. Moreover, offspring born to females with oocyte-specific deletion of Mfn2 presented increased weight gain and glucose intolerance. This abnormal phenotype was linked to decreased insulinemia and defective insulin signaling, but not mitochondrial and ER defects in offspring liver and skeletal muscle. In conclusion, this study suggests a link between disrupted mitochondrial\/ER function in oocytes and increased risk of metabolic diseases in the progeny. Future studies should determine whether MERC architecture and function are altered in oocytes from obese females, which might contribute toward transgenerational transmission of metabolic diseases.<\/jats:p>","DOI":"10.1093\/molehr\/gaaa071","type":"journal-article","created":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T15:16:39Z","timestamp":1602688599000},"page":"938-952","source":"Crossref","is-referenced-by-count":9,"title":["Mice born to females with oocyte-specific deletion of mitofusin 2 have increased weight gain and impaired glucose homeostasis"],"prefix":"10.1093","volume":"26","author":[{"given":"Bruna M","family":"Garcia","sequence":"first","affiliation":[{"name":"Departamento de Gen\u00e9tica e Evolu\u00e7\u00e3o , Universidade Federal de S\u00e3o Carlos, S\u00e3o Carlos 13565-905,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago S","family":"Machado","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Evolu\u00e7\u00e3o , Universidade Federal de S\u00e3o Carlos, S\u00e3o Carlos 13565-905,","place":["Brazil"]},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Anatomia dos Animais Dom\u00e9sticos e Silvestres, Faculdade de Medicina Veterin\u00e1ria e Zootecnia , Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-270,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen F","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Evolu\u00e7\u00e3o , Universidade Federal de S\u00e3o Carlos, S\u00e3o Carlos 13565-905,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia","family":"Nolasco","sequence":"additional","affiliation":[{"name":"Translational Cardiovascular Biology Unit, Instituto do Cora\u00e7\u00e3o , Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05403-904,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo P","family":"Nociti","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Veterin\u00e1ria, Faculdade de Zootecnia e Engenharia de Alimentos , Universidade de S\u00e3o Paulo, Pirassununga 13635-900,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maite","family":"del Collado","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Veterin\u00e1ria, Faculdade de Zootecnia e Engenharia de Alimentos , Universidade de S\u00e3o Paulo, Pirassununga 13635-900,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J D","family":"Capo Bianco","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Evolu\u00e7\u00e3o , Universidade Federal de S\u00e3o Carlos, S\u00e3o Carlos 13565-905,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateus P","family":"Grejo","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Evolu\u00e7\u00e3o , Universidade Federal de S\u00e3o Carlos, S\u00e3o Carlos 13565-905,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Djaci","family":"Augusto Neto","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Evolu\u00e7\u00e3o , Universidade Federal de S\u00e3o Carlos, S\u00e3o Carlos 13565-905,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabr\u00edcia H C","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Evolu\u00e7\u00e3o , Universidade Federal de S\u00e3o Carlos, S\u00e3o Carlos 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, University of Campinas, Campinas 13083-865,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Perecin","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Anatomia dos Animais Dom\u00e9sticos e Silvestres, Faculdade de Medicina Veterin\u00e1ria e Zootecnia , Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-270,","place":["Brazil"]},{"name":"Departamento de Medicina Veterin\u00e1ria, Faculdade de Zootecnia e Engenharia de Alimentos , Universidade de S\u00e3o Paulo, Pirassununga 13635-900,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1vio V","family":"Meirelles","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Anatomia dos Animais Dom\u00e9sticos e Silvestres, Faculdade de Medicina Veterin\u00e1ria e Zootecnia , Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-270,","place":["Brazil"]},{"name":"Departamento de Medicina Veterin\u00e1ria, Faculdade de Zootecnia e Engenharia de Alimentos , Universidade de S\u00e3o Paulo, Pirassununga 13635-900,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Bento S","family":"Ferraz","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Veterin\u00e1ria, Faculdade de Zootecnia e Engenharia de Alimentos , Universidade de S\u00e3o Paulo, Pirassununga 13635-900,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emerielle C","family":"Vanzela","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biology , University of Campinas, Campinas 13083-865,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ant\u00f4nio C","family":"Boschero","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional 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S\u00e3o Paulo 05403-904,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia J","family":"Kowaltowski","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Instituto de Qu\u00edmica , Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-900,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8805-9469","authenticated-orcid":false,"given":"Marcos R","family":"Chiaratti","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Evolu\u00e7\u00e3o , Universidade Federal de S\u00e3o Carlos, S\u00e3o Carlos 13565-905,","place":["Brazil"]},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Anatomia dos Animais Dom\u00e9sticos e Silvestres, Faculdade de Medicina Veterin\u00e1ria e Zootecnia , Universidade de S\u00e3o Paulo, S\u00e3o Paulo 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