2024-03-29T13:22:33Z
https://tsukuba.repo.nii.ac.jp/oai
oai:tsukuba.repo.nii.ac.jp:00039470
2023-02-09T02:15:21Z
2780:1784
2780:5356
2780:5462
3:62:5298:5294
KLF15 Enables Rapid Switching between Lipogenesis and Gluconeogenesis during Fasting
武内, 謙憲
タケウチ, ヨシノリ
TAKEUCHI, Yoshinori
矢作, 直也
ヤハギ, ナオヤ
YAHAGI, Naoya
會田, 雄一
アイタ, ユウイチ
AITA, Yuichi
Murayama, Yuki
Sawada, Yoshikazu
Piao, Xiaoying
Toya, Naoki
Oya, Yukari
Shikama, Akito
Takarada, Ayako
Masuda, Yukari
Nishi, Makiko
Kubota, Midori
Izumida, Yoshihiko
Yamamoto, Takashi
Sekiya, Motohiro
Matsuzaka, Takashi
Nakagawa, Yoshimi
Urayama, Osamu
Kawakami, Yasushi
Iizuka, Yoko
Gotoda, Takanari
Itaka, Keiji
Kataoka, Kazunori
Nagai, Ryozo
Kadowaki, Takashi
Yamada, Nobuhiro
Lu, Yuan
Jain, Mukesh?K.
Shimano, Hitoshi
open access
(c) 2016 The Authors.
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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.
Cell Press
2016-08
eng
journal article
VoR
http://hdl.handle.net/2241/00144139
https://tsukuba.repo.nii.ac.jp/records/39470
27545894
https://doi.org/10.1016/j.celrep.2016.07.069
2211-1247
Cell Reports
16
9
2373
2386
https://tsukuba.repo.nii.ac.jp/record/39470/files/CR_16-9.pdf
application/pdf
4.1 MB
2016-10-19