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In this study, we investigated additional mechanisms that might play a role in aggravating hepatic steatosis in\n                      <jats:italic>Sirt3<\/jats:italic>\n                      -deficient mice fed a high-fat diet (HFD).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Studies were conducted in wild-type (WT) and Sirt3\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice fed a standard diet or a HFD and in\n                      <jats:italic>SIRT3<\/jats:italic>\n                      -knockdown human Huh-7 hepatoma cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sirt3\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice fed a HFD presented exacerbated hepatic steatosis that was accompanied by decreased expression and DNA-binding activity of peroxisome proliferator-activated receptor (PPAR) \u03b1 and of several of its target genes involved in fatty acid oxidation, compared to WT mice fed the HFD. Interestingly,\n                      <jats:italic>Sirt3<\/jats:italic>\n                      deficiency in liver and its knockdown in Huh-7 cells resulted in upregulation of the nuclear levels of LIPIN1, a PPAR\u03b1 co-activator, and of the protein that controls its levels and localization, hypoxia-inducible factor 1\u03b1 (HIF-1\u03b1). These changes were prevented by lipid exposure through a mechanism that might involve a decrease in succinate levels. Finally,\n                      <jats:italic>Sirt3<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice fed the HFD showed increased levels of some proteins involved in lipid uptake, such as CD36 and the VLDL receptor. The upregulation in CD36 was confirmed in Huh-7 cells treated with a SIRT3 inhibitor or transfected with SIRT3 siRNA and incubated with palmitate, an effect that was prevented by the Nrf2 inhibitor ML385.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings demonstrate new mechanisms by which Sirt3 deficiency contributes to hepatic steatosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s12964-020-00640-8","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T14:03:52Z","timestamp":1599746632000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["SIRT3 deficiency exacerbates fatty liver by attenuating the HIF1\u03b1-LIPIN 1 pathway and increasing CD36 through Nrf2"],"prefix":"10.1186","volume":"18","author":[{"given":"Emma","family":"Barroso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosal\u00eda","family":"Rodr\u00edguez-Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Zarei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Pizarro-Degado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Planavila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Palomer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesc","family":"Villarroya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7138-8207","authenticated-orcid":false,"given":"Manuel","family":"V\u00e1zquez-Carrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"640_CR1","doi-asserted-by":"crossref","first-page":"14447","DOI":"10.1073\/pnas.0803790105","volume":"105","author":"BH Ahn","year":"2008","unstructured":"Ahn BH, Kim HS, Song S, Lee IH, Liu J, Vassilopoulos A, Deng CX, Finkel T. 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