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In this study, we aimed to document the impact of loss of mitofusin 1 (\n                      <jats:italic>Mfn1<\/jats:italic>\n                      ) or 2 (\n                      <jats:italic>Mfn2)<\/jats:italic>\n                      on adipogenesis in cultured cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We characterised adipocyte differentiation of wildtype (WT),\n                      <jats:italic>Mfn1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>-\/-<\/jats:italic>\n                      <\/jats:sup>\n                      and\n                      <jats:italic>Mfn2<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>-\/-<\/jats:italic>\n                      <\/jats:sup>\n                      mouse embryonic fibroblasts (MEFs) and 3T3-L1 preadipocytes in which Mfn1 or 2 levels were reduced using siRNA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Mfn1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>-\/-<\/jats:italic>\n                      <\/jats:sup>\n                      MEFs displayed striking fragmentation of the mitochondrial network, with surprisingly enhanced propensity to differentiate into adipocytes, as assessed by lipid accumulation, expression of adipocyte markers (\n                      <jats:italic>Plin1<\/jats:italic>\n                      ,\n                      <jats:italic>Fabp4<\/jats:italic>\n                      ,\n                      <jats:italic>Glut4<\/jats:italic>\n                      ,\n                      <jats:italic>Adipoq<\/jats:italic>\n                      ), and insulin-stimulated glucose uptake. RNA sequencing revealed a corresponding pro-adipogenic transcriptional profile including\n                      <jats:italic>Pparg<\/jats:italic>\n                      upregulation.\n                      <jats:italic>Mfn2<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>-\/-<\/jats:italic>\n                      <\/jats:sup>\n                      MEFs also had a disrupted mitochondrial morphology, but in contrast to\n                      <jats:italic>Mfn1<\/jats:italic>\n                      <jats:sup>-\/-<\/jats:sup>\n                      MEFs they showed reduced expression of adipocyte markers.\n                      <jats:italic>Mfn1<\/jats:italic>\n                      and\n                      <jats:italic>Mfn2<\/jats:italic>\n                      siRNA mediated knockdown studies in 3T3-L1 adipocytes generally replicated these findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Loss of\n                      <jats:italic>Mfn1<\/jats:italic>\n                      but not\n                      <jats:italic>Mfn2<\/jats:italic>\n                      in cultured pre-adipocyte models is pro-adipogenic. This suggests distinct, non-redundant roles for the two mitofusin orthologues in adipocyte differentiation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0306243","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T13:49:01Z","timestamp":1735652941000},"page":"e0306243","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Loss of Mfn1 but not Mfn2 enhances adipogenesis"],"prefix":"10.1371","volume":"19","author":[{"given":"Jake P.","family":"Mann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Carlos","family":"T\u00e1bara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pushpa","family":"Pushpa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Alvarez-Guaita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afreen","family":"Haider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koini","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panna","family":"Tandon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Scurria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E. 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