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
N1 - Publisher Copyright:
© 2019, The Author(s).
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.
UR - http://www.scopus.com/inward/record.url?scp=85062290562&partnerID=8YFLogxK
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 -