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Citations to this article

GRP78 expression inhibits insulin and ER stress–induced SREBP-1c activation and reduces hepatic steatosis in mice
Hélène L. Kammoun, … , Pascal Ferré, Fabienne Foufelle
Hélène L. Kammoun, … , Pascal Ferré, Fabienne Foufelle
Published April 13, 2009
Citation Information: J Clin Invest. 2009;119(5):1201-1215. https://doi.org/10.1172/JCI37007.
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Research Article Metabolism Article has an altmetric score of 4

GRP78 expression inhibits insulin and ER stress–induced SREBP-1c activation and reduces hepatic steatosis in mice

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Abstract

Hepatic steatosis is present in insulin-resistant obese rodents and is concomitant with active lipogenesis. Hepatic lipogenesis depends on the insulin-induced activation of the transcription factor SREBP-1c. Despite prevailing insulin resistance, SREBP-1c is activated in the livers of genetically and diet-induced obese rodents. Recent studies have reported the presence of an ER stress response in the livers of obese ob/ob mice. To assess whether ER stress promotes SREBP-1c activation and thus contributes to lipogenesis, we overexpressed the chaperone glucose-regulated protein 78 (GRP78) in the livers of ob/ob mice using an adenoviral vector. GRP78 overexpression reduced ER stress markers and inhibited SREBP-1c cleavage and the expression of SREBP-1c and SREBP-2 target genes. Furthermore, hepatic triglyceride and cholesterol contents were reduced, and insulin sensitivity improved, in GRP78-injected mice. These metabolic improvements were likely mediated by restoration of IRS-2 expression and tyrosine phosphorylation. Interestingly, GRP78 overexpression also inhibited insulin-induced SREBP-1c cleavage in cultured primary hepatocytes. These findings demonstrate that GRP78 inhibits both insulin-dependent and ER stress–dependent SREBP-1c proteolytic cleavage and explain the role of ER stress in hepatic steatosis in obese rodents.

Authors

Hélène L. Kammoun, Hervé Chabanon, Isabelle Hainault, Serge Luquet, Christophe Magnan, Tatsuro Koike, Pascal Ferré, Fabienne Foufelle

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 Total
Citations: 7 16 23 18 21 23 17 23 24 31 23 26 29 26 23 21 5 356
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Citations to this article in year 2017 (24)

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Julie Horwath, Chansol Hurr, Scott Butler, Mallik Guruju, Martin Cassell, Allyn L Mark, Robin Davisson, Colin Young
JCI Insight 2017
SREBP-regulated lipid metabolism: convergent physiology — divergent pathophysiology
H Shimano, R Sato
Nature Reviews Endocrinology 2017
FXR/TGR5 Dual Agonist Prevents Progression of Nephropathy in Diabetes and Obesity
XX Wang, D Wang, Y Luo, K Myakala, E Dobrinskikh, AZ Rosenberg, J Levi, JB Kopp, A Field, A Hill, S Lucia, L Qiu, T Jiang, Y Peng, D Orlicky, G Garcia, M Herman-Edelstein, V DAgati, K Henriksen, L Adorini, M Pruzanski, C Xie, KW Krausz, FJ Gonzalez, S Ranjit, A Dvornikov, E Gratton, M Levi
Journal of the American Society of Nephrology : JASN 2017
Astragaloside IV attenuates free fatty acid-induced ER stress and lipid accumulation in hepatocytes via AMPK activation
B Zhou, D Zhou, X Wei, R Zhong, J Xu, L Sun
Acta Pharmacologica Sinica 2017
Loss of Calreticulin Uncovers a Critical Role for Calcium in Regulating Cellular Lipid Homeostasis
WA Wang, WX Liu, S Durnaoglu, SK Lee, J Lian, R Lehner, J Ahnn, LB Agellon, M Michalak
Scientific Reports 2017
Levels of Hepatic Activating Transcription Factor 6 and Caspase-3 Are Downregulated in Mice after Excessive Training
AP Pinto, AL da Rocha, LC Oliveira, GP Morais, LG de Vicente, DE Cintra, JR Pauli, LP Moura, ER Ropelle, AS da Silva
Frontiers in Endocrinology 2017
Endoplasmic reticulum stress inhibits expression of genes involved in thyroid hormone synthesis and their key transcriptional regulators in FRTL-5 thyrocytes
G Wen, R Ringseis, K Eder, DY Jin
PloS one 2017
Hepatocyte-specific deletion of BAP31 promotes SREBP1C activation, promotes hepatic lipid accumulation, and worsens IR in mice
JL Xu, LY Li, YQ Wang, YQ Li, M Shan, SZ Sun, Y Yu, B Wang
Journal of lipid research 2017
The role of declining adaptive homeostasis in ageing: Ageing decline in adaptive homeostasis
LC Pomatto, KJ Davies
The Journal of Physiology 2017
Sterol regulatory element-binding protein-1c orchestrates metabolic remodeling of white adipose tissue by caloric restriction
N Fujii, T Narita, N Okita, M Kobayashi, Y Furuta, Y Chujo, M Sakai, A Yamada, K Takeda, T Konishi, Y Sudo, I Shimokawa, Y Higami
Aging Cell 2017
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GK Bandyopadhyay, SK Mahata
Frontiers in Endocrinology 2017
Brain Ceramide Metabolism in the Control of Energy Balance
C Cruciani-Guglielmacci, M López, M Campana, H Stunff
Frontiers in physiology 2017
Impact of High Cholesterol and Endoplasmic Reticulum Stress on Metabolic Diseases: An Updated Mini-Review
E Sozen, NK Ozer
Redox Biology 2017
Modeling Acute ER Stress in Vivo and in Vitro:
A Abdullahi, M Stanojcic, A Parousis, D Patsouris, MG Jeschke
Shock 2017
An endoplasmic reticulum protein, Nogo-B, facilitates alcoholic liver disease through regulation of kupffer cell polarization
JK Park, M Shao, MY Kim, SK Baik, MY Cho, T Utsumi, A Satoh, X Ouyang, C Chung, Y Iwakiri
Hepatology 2017
GRP78 at the Centre of the Stage in Cancer and Neuroprotection
C Casas
Frontiers in neuroscience 2017
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JQ Li, YL Qiu, JY Gong, LM Dou, Y Lu, AS Knisely, MH Zhang, WS Luan, JS Wang
BMC Gastroenterology 2017
Inhibition of hepatocyte nuclear factor 1b induces hepatic steatosis through DPP4/NOX1-mediated regulation of superoxide
Z Long, M Cao, S Su, G Wu, F Meng, H Wu, J Liu, W Yu, K Atabai, X Wang
Free radical biology & medicine 2017
Lipid environment induces ER stress, TXNIP expression and inflammation in immune cells of individuals with type 2 diabetes
A Szpigel, I Hainault, A Carlier, N Venteclef, AF Batto, E Hajduch, C Bernard, A Ktorza, JF Gautier, P Ferré, O Bourron, F Foufelle
Diabetologia 2017
Dysregulated expression of proteins associated with ER stress, autophagy and apoptosis in tissues from nonalcoholic fatty liver disease
S Lee, S Kim, S Hwang, NJ Cherrington, DY Ryu
Oncotarget 2017
Slfn2 mutation-induced loss of T-cell quiescence leads to elevated de novo sterol synthesis
I Omar, O Rom, M Aviram, L Cohen-Daniel, AK Gebre, JS Parks, M Berger
Immunology 2017
Added fructose as a principal driver of non-alcoholic fatty liver disease: a public health crisis
JJ DiNicolantonio, AM Subramonian, JH OKeefe
Open Heart 2017
Hypothalamic GRP78, a new target against obesity?
C Contreras, MF Fondevila, M López
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Defective STIM-mediated store operated Ca2+ entry in hepatocytes leads to metabolic dysfunction in obesity
AP Arruda, BM Pers, G Parlakgul, E Güney, T Goh, E Cagampan, GY Lee, RL Goncalves, GS Hotamisligil
eLife 2017

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