Hepatic Sdf2l1 controls feeding-induced ER stress and regulates metabolism

Takayoshi Sasako; Mitsuru Ohsugi; Naoto Kubota; Shinsuke Itoh; Yukiko Okazaki; Ai Terai; Tetsuya Kubota; Satoshi Yamashita; Kunio Nakatsukasa; Takumi Kamura; Kaito Iwayama; Kumpei Tokuyama; Hiroshi Kiyonari; Yasuhide Furuta; Junji Shibahara; Masashi Fukayama; Kenichiro Enooku; Kazuya Okushin; Takeya Tsutsumi; Ryosuke Tateishi; Kazuyuki Tobe; Hiroshi Asahara; Kazuhiko Koike; Takashi Kadowaki; Kohjiro Ueki

doi:10.1038/s41467-019-08591-6

Hepatic Sdf2l1 controls feeding-induced ER stress and regulates metabolism

Takayoshi Sasako, Mitsuru Ohsugi, Naoto Kubota, Shinsuke Itoh, Yukiko Okazaki, Ai Terai, Tetsuya Kubota, Satoshi Yamashita, Kunio Nakatsukasa, Takumi Kamura, Kaito Iwayama, Kumpei Tokuyama, Hiroshi Kiyonari, Yasuhide Furuta, Junji Shibahara, Masashi Fukayama, Kenichiro Enooku, Kazuya Okushin, Takeya Tsutsumi, Ryosuke TateishiKazuyuki Tobe, Hiroshi Asahara, Kazuhiko Koike, Takashi Kadowaki^*, Kohjiro Ueki

^*Corresponding author for this work

Faculty of Medicine

Research output: Contribution to journal › Article › peer-review

64 Scopus citations

Abstract

Dynamic metabolic changes occur in the liver during the transition between fasting and feeding. Here we show that transient ER stress responses in the liver following feeding terminated by Sdf2l1 are essential for normal glucose and lipid homeostasis. Sdf2l1 regulates ERAD through interaction with a trafficking protein, TMED10. Suppression of Sdf2l1 expression in the liver results in insulin resistance and increases triglyceride content with sustained ER stress. In obese and diabetic mice, Sdf2l1 is downregulated due to decreased levels of nuclear XBP-1s, whereas restoration of Sdf2l1 expression ameliorates glucose intolerance and fatty liver with decreased ER stress. In diabetic patients, insufficient induction of Sdf2l1 correlates with progression of insulin resistance and steatohepatitis. Therefore, failure to build an ER stress response in the liver may be a causal factor in obesity-related diabetes and nonalcoholic steatohepatitis, for which Sdf2l1 could serve as a therapeutic target and sensitive biomarker.

Original language	English
Article number	947
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-08591-6
State	Published - 2019/12/01

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Sasako, T., Ohsugi, M., Kubota, N., Itoh, S., Okazaki, Y., Terai, A., Kubota, T., Yamashita, S., Nakatsukasa, K., Kamura, T., Iwayama, K., Tokuyama, K., Kiyonari, H., Furuta, Y., Shibahara, J., Fukayama, M., Enooku, K., Okushin, K., Tsutsumi, T., ... Ueki, K. (2019). Hepatic Sdf2l1 controls feeding-induced ER stress and regulates metabolism. Nature Communications, 10(1), Article 947. https://doi.org/10.1038/s41467-019-08591-6

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abstract = "Dynamic metabolic changes occur in the liver during the transition between fasting and feeding. Here we show that transient ER stress responses in the liver following feeding terminated by Sdf2l1 are essential for normal glucose and lipid homeostasis. Sdf2l1 regulates ERAD through interaction with a trafficking protein, TMED10. Suppression of Sdf2l1 expression in the liver results in insulin resistance and increases triglyceride content with sustained ER stress. In obese and diabetic mice, Sdf2l1 is downregulated due to decreased levels of nuclear XBP-1s, whereas restoration of Sdf2l1 expression ameliorates glucose intolerance and fatty liver with decreased ER stress. In diabetic patients, insufficient induction of Sdf2l1 correlates with progression of insulin resistance and steatohepatitis. Therefore, failure to build an ER stress response in the liver may be a causal factor in obesity-related diabetes and nonalcoholic steatohepatitis, for which Sdf2l1 could serve as a therapeutic target and sensitive biomarker.",

author = "Takayoshi Sasako and Mitsuru Ohsugi and Naoto Kubota and Shinsuke Itoh and Yukiko Okazaki and Ai Terai and Tetsuya Kubota and Satoshi Yamashita and Kunio Nakatsukasa and Takumi Kamura and Kaito Iwayama and Kumpei Tokuyama and Hiroshi Kiyonari and Yasuhide Furuta and Junji Shibahara and Masashi Fukayama and Kenichiro Enooku and Kazuya Okushin and Takeya Tsutsumi and Ryosuke Tateishi and Kazuyuki Tobe and Hiroshi Asahara and Kazuhiko Koike and Takashi Kadowaki and Kohjiro Ueki",

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doi = "10.1038/s41467-019-08591-6",

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Sasako, T, Ohsugi, M, Kubota, N, Itoh, S, Okazaki, Y, Terai, A, Kubota, T, Yamashita, S, Nakatsukasa, K, Kamura, T, Iwayama, K, Tokuyama, K, Kiyonari, H, Furuta, Y, Shibahara, J, Fukayama, M, Enooku, K, Okushin, K, Tsutsumi, T, Tateishi, R, Tobe, K, Asahara, H, Koike, K, Kadowaki, T & Ueki, K 2019, 'Hepatic Sdf2l1 controls feeding-induced ER stress and regulates metabolism', Nature Communications, vol. 10, no. 1, 947. https://doi.org/10.1038/s41467-019-08591-6

TY - JOUR

T1 - Hepatic Sdf2l1 controls feeding-induced ER stress and regulates metabolism

AU - Sasako, Takayoshi

AU - Ohsugi, Mitsuru

AU - Kubota, Naoto

AU - Itoh, Shinsuke

AU - Okazaki, Yukiko

AU - Terai, Ai

AU - Kubota, Tetsuya

AU - Yamashita, Satoshi

AU - Nakatsukasa, Kunio

AU - Kamura, Takumi

AU - Iwayama, Kaito

AU - Tokuyama, Kumpei

AU - Kiyonari, Hiroshi

AU - Furuta, Yasuhide

AU - Shibahara, Junji

AU - Fukayama, Masashi

AU - Enooku, Kenichiro

AU - Okushin, Kazuya

AU - Tsutsumi, Takeya

AU - Tateishi, Ryosuke

AU - Tobe, Kazuyuki

AU - Asahara, Hiroshi

AU - Koike, Kazuhiko

AU - Kadowaki, Takashi

AU - Ueki, Kohjiro

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Dynamic metabolic changes occur in the liver during the transition between fasting and feeding. Here we show that transient ER stress responses in the liver following feeding terminated by Sdf2l1 are essential for normal glucose and lipid homeostasis. Sdf2l1 regulates ERAD through interaction with a trafficking protein, TMED10. Suppression of Sdf2l1 expression in the liver results in insulin resistance and increases triglyceride content with sustained ER stress. In obese and diabetic mice, Sdf2l1 is downregulated due to decreased levels of nuclear XBP-1s, whereas restoration of Sdf2l1 expression ameliorates glucose intolerance and fatty liver with decreased ER stress. In diabetic patients, insufficient induction of Sdf2l1 correlates with progression of insulin resistance and steatohepatitis. Therefore, failure to build an ER stress response in the liver may be a causal factor in obesity-related diabetes and nonalcoholic steatohepatitis, for which Sdf2l1 could serve as a therapeutic target and sensitive biomarker.

AB - Dynamic metabolic changes occur in the liver during the transition between fasting and feeding. Here we show that transient ER stress responses in the liver following feeding terminated by Sdf2l1 are essential for normal glucose and lipid homeostasis. Sdf2l1 regulates ERAD through interaction with a trafficking protein, TMED10. Suppression of Sdf2l1 expression in the liver results in insulin resistance and increases triglyceride content with sustained ER stress. In obese and diabetic mice, Sdf2l1 is downregulated due to decreased levels of nuclear XBP-1s, whereas restoration of Sdf2l1 expression ameliorates glucose intolerance and fatty liver with decreased ER stress. In diabetic patients, insufficient induction of Sdf2l1 correlates with progression of insulin resistance and steatohepatitis. Therefore, failure to build an ER stress response in the liver may be a causal factor in obesity-related diabetes and nonalcoholic steatohepatitis, for which Sdf2l1 could serve as a therapeutic target and sensitive biomarker.

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U2 - 10.1038/s41467-019-08591-6

DO - 10.1038/s41467-019-08591-6

M3 - 学術論文

C2 - 30814508

AN - SCOPUS:85062290562

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 947

ER -

Hepatic Sdf2l1 controls feeding-induced ER stress and regulates metabolism

Abstract

ASJC Scopus subject areas

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