MicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice

Takahiro Horie, Tomohiro Nishino, Osamu Baba, Yasuhide Kuwabara, Tetsushi Nakao, Masataka Nishiga, Shunsuke Usami, Masayasu Izuhara, Naoya Sowa, Naoya Yahagi, Hitoshi Shimano, Shigenobu Matsumura, Kazuo Inoue, Hiroyuki Marusawa, Tomoyuki Nakamura, Koji Hasegawa, Noriaki Kume, Masayuki Yokode, Toru Kita, Takeshi Kimura and Koh Ono ()
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Takahiro Horie: Graduate School of Medicine, Kyoto University
Tomohiro Nishino: Graduate School of Medicine, Kyoto University
Osamu Baba: Graduate School of Medicine, Kyoto University
Yasuhide Kuwabara: Graduate School of Medicine, Kyoto University
Tetsushi Nakao: Graduate School of Medicine, Kyoto University
Masataka Nishiga: Graduate School of Medicine, Kyoto University
Shunsuke Usami: Graduate School of Medicine, Kyoto University
Masayasu Izuhara: Graduate School of Medicine, Kyoto University
Naoya Sowa: Graduate School of Medicine, Kyoto University
Naoya Yahagi: Graduate School of Comprehensive Human Sciences, Nutrigenomics Research Group, Faculty of Medicine, and International Institute for Integrative Sleep Medicine (IIIS), World Premir International Research Center Initiative (WPI), University of Tsukuba
Hitoshi Shimano: Graduate School of Comprehensive Human Sciences, Nutrigenomics Research Group, Faculty of Medicine, and International Institute for Integrative Sleep Medicine (IIIS), World Premir International Research Center Initiative (WPI), University of Tsukuba
Shigenobu Matsumura: Laboratory of Nutrition Chemistry, Graduate School of Agriculture, Kyoto University
Kazuo Inoue: Laboratory of Nutrition Chemistry, Graduate School of Agriculture, Kyoto University
Hiroyuki Marusawa: Graduate School of Medicine, Kyoto University
Tomoyuki Nakamura: Kansai Medical University
Koji Hasegawa: National Hospital Organization, Kyoto Medical Center
Noriaki Kume: Faculty of Pharmaceutical Sciences, Kobe Gakuin University
Masayuki Yokode: Institute for Advancement of Clinical and Translational Science, Graduate School of Medicine, Kyoto University
Toru Kita: Kobe City Medical Center General Hospital
Takeshi Kimura: Graduate School of Medicine, Kyoto University
Koh Ono: Graduate School of Medicine, Kyoto University

Nature Communications, 2013, vol. 4, issue 1, 1-12

Abstract: Abstract MicroRNAs (miRs) are small non-protein-coding RNAs that bind to specific mRNAs and inhibit translation or promote mRNA degradation. Recent reports have indicated that miR-33, which is located within the intron of sterol regulatory element-binding protein (SREBP) 2, controls cholesterol homoeostasis and may be a potential therapeutic target for the treatment of atherosclerosis. Here we show that deletion of miR-33 results in marked worsening of high-fat diet-induced obesity and liver steatosis. Using miR-33−/−Srebf1+/− mice, we demonstrate that SREBP-1 is a target of miR-33 and that the mechanisms leading to obesity and liver steatosis in miR-33−/− mice involve enhanced expression of SREBP-1. These results elucidate a novel interaction between SREBP-1 and SREBP-2 mediated by miR-33 in vivo.

Date: 2013
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DOI: 10.1038/ncomms3883

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