FoxO-KLF15 pathway switches the flow of macronutrients under the control of insulin

Summary: KLF15 is a transcription factor that plays an important role in the activation of gluconeogenesis from amino acids as well as the suppression of lipogenesis from glucose. Here we identified the transcription start site of liver-specific KLF15 transcript and showed that FoxO1/3 transcription...

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Autores principales:	Yoshinori Takeuchi, Naoya Yahagi, Yuichi Aita, Zahra Mehrazad-Saber, Man Hei Ho, Yiren Huyan, Yuki Murayama, Akito Shikama, Yukari Masuda, Yoshihiko Izumida, Takafumi Miyamoto, Takashi Matsuzaka, Yasushi Kawakami, Hitoshi Shimano
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Molecular biology Molecular network Diabetology Science Q
Acceso en línea:	https://doaj.org/article/511b0e2c3c3a4100b159be803e5ed024
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spelling	oai:doaj.org-article:511b0e2c3c3a4100b159be803e5ed0242021-11-28T04:36:33ZFoxO-KLF15 pathway switches the flow of macronutrients under the control of insulin2589-004210.1016/j.isci.2021.103446https://doaj.org/article/511b0e2c3c3a4100b159be803e5ed0242021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221014176https://doaj.org/toc/2589-0042Summary: KLF15 is a transcription factor that plays an important role in the activation of gluconeogenesis from amino acids as well as the suppression of lipogenesis from glucose. Here we identified the transcription start site of liver-specific KLF15 transcript and showed that FoxO1/3 transcriptionally regulates Klf15 gene expression by directly binding to the liver-specific Klf15 promoter. To achieve this, we performed a precise in vivo promoter analysis combined with the genome-wide transcription-factor-screening method “TFEL scan”, using our original Transcription Factor Expression Library (TFEL), which covers nearly all the transcription factors in the mouse genome. Hepatic Klf15 expression is significantly increased via FoxOs by attenuating insulin signaling. Furthermore, FoxOs elevate the expression levels of amino acid catabolic enzymes and suppress SREBP-1c via KLF15, resulting in accelerated amino acid breakdown and suppressed lipogenesis during fasting. Thus, the FoxO-KLF15 pathway contributes to switching the macronutrient flow in the liver under the control of insulin.Yoshinori TakeuchiNaoya YahagiYuichi AitaZahra Mehrazad-SaberMan Hei HoYiren HuyanYuki MurayamaAkito ShikamaYukari MasudaYoshihiko IzumidaTakafumi MiyamotoTakashi MatsuzakaYasushi KawakamiHitoshi ShimanoElsevierarticleMolecular biologyMolecular networkDiabetologyScienceQENiScience, Vol 24, Iss 12, Pp 103446- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Molecular biology Molecular network Diabetology Science Q
spellingShingle	Molecular biology Molecular network Diabetology Science Q Yoshinori Takeuchi Naoya Yahagi Yuichi Aita Zahra Mehrazad-Saber Man Hei Ho Yiren Huyan Yuki Murayama Akito Shikama Yukari Masuda Yoshihiko Izumida Takafumi Miyamoto Takashi Matsuzaka Yasushi Kawakami Hitoshi Shimano FoxO-KLF15 pathway switches the flow of macronutrients under the control of insulin
description	Summary: KLF15 is a transcription factor that plays an important role in the activation of gluconeogenesis from amino acids as well as the suppression of lipogenesis from glucose. Here we identified the transcription start site of liver-specific KLF15 transcript and showed that FoxO1/3 transcriptionally regulates Klf15 gene expression by directly binding to the liver-specific Klf15 promoter. To achieve this, we performed a precise in vivo promoter analysis combined with the genome-wide transcription-factor-screening method “TFEL scan”, using our original Transcription Factor Expression Library (TFEL), which covers nearly all the transcription factors in the mouse genome. Hepatic Klf15 expression is significantly increased via FoxOs by attenuating insulin signaling. Furthermore, FoxOs elevate the expression levels of amino acid catabolic enzymes and suppress SREBP-1c via KLF15, resulting in accelerated amino acid breakdown and suppressed lipogenesis during fasting. Thus, the FoxO-KLF15 pathway contributes to switching the macronutrient flow in the liver under the control of insulin.
format	article
author	Yoshinori Takeuchi Naoya Yahagi Yuichi Aita Zahra Mehrazad-Saber Man Hei Ho Yiren Huyan Yuki Murayama Akito Shikama Yukari Masuda Yoshihiko Izumida Takafumi Miyamoto Takashi Matsuzaka Yasushi Kawakami Hitoshi Shimano
author_facet	Yoshinori Takeuchi Naoya Yahagi Yuichi Aita Zahra Mehrazad-Saber Man Hei Ho Yiren Huyan Yuki Murayama Akito Shikama Yukari Masuda Yoshihiko Izumida Takafumi Miyamoto Takashi Matsuzaka Yasushi Kawakami Hitoshi Shimano
author_sort	Yoshinori Takeuchi
title	FoxO-KLF15 pathway switches the flow of macronutrients under the control of insulin
title_short	FoxO-KLF15 pathway switches the flow of macronutrients under the control of insulin
title_full	FoxO-KLF15 pathway switches the flow of macronutrients under the control of insulin
title_fullStr	FoxO-KLF15 pathway switches the flow of macronutrients under the control of insulin
title_full_unstemmed	FoxO-KLF15 pathway switches the flow of macronutrients under the control of insulin
title_sort	foxo-klf15 pathway switches the flow of macronutrients under the control of insulin
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/511b0e2c3c3a4100b159be803e5ed024
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FoxO-KLF15 pathway switches the flow of macronutrients under the control of insulin

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