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Hepatic Sdf2l1 controls feeding-induced ER stress and regulates metabolism

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...

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Autores principales: Sasako, Takayoshi, Ohsugi, Mitsuru, Kubota, Naoto, Itoh, Shinsuke, Okazaki, Yukiko, Terai, Ai, Kubota, Tetsuya, Yamashita, Satoshi, Nakatsukasa, Kunio, Kamura, Takumi, Iwayama, Kaito, Tokuyama, Kumpei, Kiyonari, Hiroshi, Furuta, Yasuhide, Shibahara, Junji, Fukayama, Masashi, Enooku, Kenichiro, Okushin, Kazuya, Tsutsumi, Takeya, Tateishi, Ryosuke, Tobe, Kazuyuki, Asahara, Hiroshi, Koike, Kazuhiko, Kadowaki, Takashi, Ueki, Kohjiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393527/
https://www.ncbi.nlm.nih.gov/pubmed/30814508
http://dx.doi.org/10.1038/s41467-019-08591-6
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author Sasako, Takayoshi
Ohsugi, Mitsuru
Kubota, Naoto
Itoh, Shinsuke
Okazaki, Yukiko
Terai, Ai
Kubota, Tetsuya
Yamashita, Satoshi
Nakatsukasa, Kunio
Kamura, Takumi
Iwayama, Kaito
Tokuyama, Kumpei
Kiyonari, Hiroshi
Furuta, Yasuhide
Shibahara, Junji
Fukayama, Masashi
Enooku, Kenichiro
Okushin, Kazuya
Tsutsumi, Takeya
Tateishi, Ryosuke
Tobe, Kazuyuki
Asahara, Hiroshi
Koike, Kazuhiko
Kadowaki, Takashi
Ueki, Kohjiro
author_facet Sasako, Takayoshi
Ohsugi, Mitsuru
Kubota, Naoto
Itoh, Shinsuke
Okazaki, Yukiko
Terai, Ai
Kubota, Tetsuya
Yamashita, Satoshi
Nakatsukasa, Kunio
Kamura, Takumi
Iwayama, Kaito
Tokuyama, Kumpei
Kiyonari, Hiroshi
Furuta, Yasuhide
Shibahara, Junji
Fukayama, Masashi
Enooku, Kenichiro
Okushin, Kazuya
Tsutsumi, Takeya
Tateishi, Ryosuke
Tobe, Kazuyuki
Asahara, Hiroshi
Koike, Kazuhiko
Kadowaki, Takashi
Ueki, Kohjiro
author_sort Sasako, Takayoshi
collection PubMed
description 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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spelling pubmed-63935272019-03-01 Hepatic Sdf2l1 controls feeding-induced ER stress and regulates metabolism Sasako, Takayoshi Ohsugi, Mitsuru Kubota, Naoto Itoh, Shinsuke Okazaki, Yukiko Terai, Ai Kubota, Tetsuya Yamashita, Satoshi Nakatsukasa, Kunio Kamura, Takumi Iwayama, Kaito Tokuyama, Kumpei Kiyonari, Hiroshi Furuta, Yasuhide Shibahara, Junji Fukayama, Masashi Enooku, Kenichiro Okushin, Kazuya Tsutsumi, Takeya Tateishi, Ryosuke Tobe, Kazuyuki Asahara, Hiroshi Koike, Kazuhiko Kadowaki, Takashi Ueki, Kohjiro Nat Commun Article 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. Nature Publishing Group UK 2019-02-27 /pmc/articles/PMC6393527/ /pubmed/30814508 http://dx.doi.org/10.1038/s41467-019-08591-6 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Sasako, Takayoshi
Ohsugi, Mitsuru
Kubota, Naoto
Itoh, Shinsuke
Okazaki, Yukiko
Terai, Ai
Kubota, Tetsuya
Yamashita, Satoshi
Nakatsukasa, Kunio
Kamura, Takumi
Iwayama, Kaito
Tokuyama, Kumpei
Kiyonari, Hiroshi
Furuta, Yasuhide
Shibahara, Junji
Fukayama, Masashi
Enooku, Kenichiro
Okushin, Kazuya
Tsutsumi, Takeya
Tateishi, Ryosuke
Tobe, Kazuyuki
Asahara, Hiroshi
Koike, Kazuhiko
Kadowaki, Takashi
Ueki, Kohjiro
Hepatic Sdf2l1 controls feeding-induced ER stress and regulates metabolism
title Hepatic Sdf2l1 controls feeding-induced ER stress and regulates metabolism
title_full Hepatic Sdf2l1 controls feeding-induced ER stress and regulates metabolism
title_fullStr Hepatic Sdf2l1 controls feeding-induced ER stress and regulates metabolism
title_full_unstemmed Hepatic Sdf2l1 controls feeding-induced ER stress and regulates metabolism
title_short Hepatic Sdf2l1 controls feeding-induced ER stress and regulates metabolism
title_sort hepatic sdf2l1 controls feeding-induced er stress and regulates metabolism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393527/
https://www.ncbi.nlm.nih.gov/pubmed/30814508
http://dx.doi.org/10.1038/s41467-019-08591-6
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