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 () and Kohjiro Ueki ()
Additional contact information
Takayoshi Sasako: The University of Tokyo
Mitsuru Ohsugi: The University of Tokyo
Naoto Kubota: The University of Tokyo
Shinsuke Itoh: The University of Tokyo
Yukiko Okazaki: The University of Tokyo
Ai Terai: The University of Tokyo
Tetsuya Kubota: The University of Tokyo
Satoshi Yamashita: Tokyo Medical and Dental University
Kunio Nakatsukasa: Nagoya University
Takumi Kamura: Nagoya University
Kaito Iwayama: University of Tsukuba
Kumpei Tokuyama: University of Tsukuba
Hiroshi Kiyonari: RIKEN Center for Life Science Technologies
Yasuhide Furuta: RIKEN Center for Life Science Technologies
Junji Shibahara: The University of Tokyo
Masashi Fukayama: The University of Tokyo
Kenichiro Enooku: The University of Tokyo
Kazuya Okushin: The University of Tokyo
Takeya Tsutsumi: The University of Tokyo
Ryosuke Tateishi: The University of Tokyo
Kazuyuki Tobe: The University of Toyama
Hiroshi Asahara: Tokyo Medical and Dental University
Kazuhiko Koike: The University of Tokyo
Takashi Kadowaki: The University of Tokyo
Kohjiro Ueki: The University of Tokyo

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-08591-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08591-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-08591-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().