Hepatic Sdf2l1 controls feeding-induced ER stress and regulates metabolism

Nature Communications
Takayoshi SasakoKohjiro Ueki

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.

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Citations

Jun 25, 2020·Oncotarget·Aejaz SayeedTimothy Block
Aug 6, 2019·Biochemical and Biophysical Research Communications·Seisuke MimoriTetsuto Kanzaki
Jan 1, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jiahui AnJun Hao
Jan 24, 2021·Molecular Metabolism·Imke L LemmerAlexander Bartelt
Feb 10, 2021·Experimental & Molecular Medicine·Kashi Raj BhattaraiHan-Jung Chae
Mar 7, 2021·International Journal of Molecular Sciences·Juncheng Wei, Deyu Fang
Mar 12, 2021·Endocrine Reviews·Amir AjoolabadyJun Ren
May 1, 2021·International Journal of Molecular Sciences·Yoshitaka SakuraiTakashi Kadowaki
May 1, 2021·International Journal of Molecular Sciences·Styliana KyriakoudiPetros P Petrou
Jan 20, 2021·The Kaohsiung Journal of Medical Sciences·Zhi-Xiong LeiPing Liu
May 18, 2021·Circulation Research·Hirofumi WatanabeMaria Luisa S Sequeira-Lopez
Oct 3, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Si-Wei XiaShi-Zhong Zheng

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Methods Mentioned

BETA
immunoprecipitation
ubiquitination
nuclear translocation
PCR
biopsy
electrophoresis
ELISA
ChIP
genotyping
Assay

Software Mentioned

EZ
R
GEO2R

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