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In the present study, we report that Kruppel-like factor 15 (KLF15) is a novel mediator of b-cell translocation gene 2 (BTG2)-induced FGF21 biosynthesis. The expression levels of hepatic\n                    <jats:italic>Fgf21<\/jats:italic>\n                    ,\n                    <jats:italic>Btg2<\/jats:italic>\n                    , and\n                    <jats:italic>Klf15<\/jats:italic>\n                    , and the production of serum FGF21 increased significantly in fasted and forskolin (FSK)-treated mice. The overexpression of\n                    <jats:italic>Btg2<\/jats:italic>\n                    using an adenoviral delivery system elevated FGF21 production by upregulating\n                    <jats:italic>Klf15<\/jats:italic>\n                    transcription. Interaction studies indicated that BTG2 was co-immunoprecipitated with KLF15 and recruited by the\n                    <jats:italic>Fgf21<\/jats:italic>\n                    promoter. The disruption of hepatic\n                    <jats:italic>Btg2<\/jats:italic>\n                    and\n                    <jats:italic>Klf15<\/jats:italic>\n                    genes markedly attenuated the induction of\n                    <jats:italic>Fgf21<\/jats:italic>\n                    expression and FGF21 biosynthesis in fasted mice. Similarly, the FSK-mediated induction of\n                    <jats:italic>Fgf21<\/jats:italic>\n                    promoter activity was strikingly ablated by silencing of\n                    <jats:italic>Btg2<\/jats:italic>\n                    and\n                    <jats:italic>Klf15<\/jats:italic>\n                    . Taken together, these findings suggest that KLF15 and BTG2 are mediators of fasting-induced hepatic FGF21 expression. Therefore, targeting BTG2 and KLF15 might be a therapeutically important strategy for combat metabolic dysfunction.\n                  <\/jats:p>","DOI":"10.1038\/s41598-019-40359-2","type":"journal-article","created":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T06:07:05Z","timestamp":1551852425000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["B-cell translocation gene 2 enhances fibroblast growth factor 21 production by inducing Kruppel-like factor 15"],"prefix":"10.1038","volume":"9","author":[{"given":"Yong Deuk","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Lark","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwang-Ju","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Hyun","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balachandar","family":"Nedumaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyeongsoon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7690-9956","authenticated-orcid":false,"given":"Sung-Eun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,6]]},"reference":[{"key":"40359_CR1","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1146\/annurev-physiol-021115-105339","volume":"78","author":"FM Fisher","year":"2016","unstructured":"Fisher, F. 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