{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T12:16:49Z","timestamp":1777983409039,"version":"3.51.4"},"reference-count":24,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,2,15]],"date-time":"2021-02-15T00:00:00Z","timestamp":1613347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims\/Introduction<\/jats:title><jats:p>Brown adipose tissue (BAT) utilizes large amounts of fuel for thermogenesis, but the mechanism by which fuel substrates are switched in response to changes in energy status is poorly understood. We have now investigated the role of Kruppel\u2010like factor\u00a015 (KLF15), a transcription factor expressed at a high level in adipose tissue, in the regulation of fuel utilization in BAT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Depletion or overexpression of KLF15 in HB2 differentiated brown adipocytes was achieved by adenoviral infection. Glucose and fatty acid oxidation were measured with radioactive substrates, pyruvate dehydrogenase complex activity was determined with a colorimetric assay, and gene expression was examined by reverse transcription and real\u2010time polymerase chain reaction analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Knockdown of KLF15 in HB2 cells attenuated fatty acid oxidation in association with downregulation of the expression of genes related to this process including <jats:italic>Acox1<\/jats:italic> and <jats:italic>Fatp1<\/jats:italic>, whereas it increased glucose oxidation. Expression of the gene for pyruvate dehydrogenase kinase\u00a04 (PDK4), a negative regulator of pyruvate dehydrogenase complex, was increased or decreased by KLF15 overexpression or knockdown, respectively, in HB2 cells, with these changes being accompanied by a respective decrease or increase in pyruvate dehydrogenase complex activity. Chromatin immunoprecipitation showed that <jats:italic>Pdk4<\/jats:italic> is a direct target of KLF15 in HB2 cells. Finally, fasting increased expression of <jats:italic>KLf15<\/jats:italic>, <jats:italic>Pdk4<\/jats:italic> and genes involved in fatty acid utilization in BAT of mice, whereas refeeding suppressed <jats:italic>Klf15<\/jats:italic> and <jats:italic>Pdk4<\/jats:italic> expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results implicate KLF15 in the regulation of fuel switching between glucose and fatty acids in response to changes in energy status in BAT.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.13511","type":"journal-article","created":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T02:38:50Z","timestamp":1611283130000},"page":"1144-1151","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Kruppel\u2010like factor\u00a015 regulates fuel switching between glucose and fatty acids in brown adipocytes"],"prefix":"10.1111","volume":"12","author":[{"given":"Yuko","family":"Nabatame","sequence":"first","affiliation":[{"name":"Division of Diabetes and Endocrinology Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9944-5418","authenticated-orcid":false,"given":"Tetsuya","family":"Hosooka","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology Kobe University Graduate School of Medicine Kobe Japan"},{"name":"Division of Development of Advanced Therapy for Metabolic Disease Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chikako","family":"Aoki","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology Kobe University Graduate School of Medicine Kobe 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