KLF15 Enables Rapid Switching between Lipogenesis and Gluconeogenesis during Fasting

Yoshinori Takeuchi, Naoya Yahagi*, Yuichi Aita, Yuki Murayama, Yoshikazu Sawada, Xiaoying Piao, Naoki Toya, Yukari Oya, Akito Shikama, Ayako Takarada, Yukari Masuda, Makiko Nishi, Midori Kubota, Yoshihiko Izumida, Takashi Yamamoto, Motohiro Sekiya, Takashi Matsuzaka, Yoshimi Nakagawa, Osamu Urayama, Yasushi KawakamiYoko Iizuka, Takanari Gotoda, Keiji Itaka, Kazunori Kataoka, Ryozo Nagai, Takashi Kadowaki, Nobuhiro Yamada, Yuan Lu, Mukesh K. Jain, Hitoshi Shimano

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

74 被引用数 (Scopus)

抄録

Hepatic lipogenesis is nutritionally regulated (i.e., downregulated during fasting and upregulated during the postprandial state) as an adaptation to the nutritional environment. While alterations in the expression level of the transcription factor SREBP-1c are known to be critical for nutritionally regulated lipogenesis, upstream mechanisms governing Srebf1 expression remain unclear. Here, we show that the fasting-induced transcription factor KLF15, a key regulator of gluconeogenesis, forms a complex with LXR/RXR, specifically on the Srebf1 promoter. This complex recruits the corepressor RIP140 instead of the coactivator SRC1, resulting in reduced Srebf1 and thus downstream lipogenic enzyme expression during the early and euglycemic period of fasting prior to hypoglycemia and PKA activation. Through this mechanism, KLF15 overexpression specifically ameliorates hypertriglyceridemia without affecting LXR-mediated cholesterol metabolism. These findings reveal a key molecular link between glucose and lipid metabolism and have therapeutic implications for the treatment of hyperlipidemia.

本文言語英語
ページ(範囲)2373-2386
ページ数14
ジャーナルCell Reports
16
9
DOI
出版ステータス出版済み - 2016/08/30

ASJC Scopus 主題領域

  • 生化学、遺伝学、分子生物学一般

フィンガープリント

「KLF15 Enables Rapid Switching between Lipogenesis and Gluconeogenesis during Fasting」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル