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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
Citation information
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Citations to this article in year 2013 (29)

Title and authors Publication Year
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GY Lee, H Jang, JH Lee, JY Huh, S Choi, J Chung, JB Kim
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Endoplasmic reticulum and the unfolded protein response: dynamics and metabolic integration
R Bravo, V Parra, D Gatica, AE Rodriguez, N Torrealba, F Paredes, ZV Wang, A Zorzano, JA Hill, E Jaimovich, AF Quest, S Lavandero
International review of cell and molecular biology 2013
Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma: Implications for Lycopene Intervention
B Ip, XD Wang
Nutrients 2013
Zidovudine (AZT) and hepatic lipid accumulation: implication of inflammation, oxidative and endoplasmic reticulum stress mediators
A Banerjee, MA Abdelmegeed, S Jang, BJ Song
PloS one 2013
Unfolded Protein Response Signaling and Metabolic Diseases
J Lee, U Ozcan
The Journal of biological chemistry 2013
The role of the unfolded protein response in diabetes mellitus
T Iwawaki, D Oikawa
Seminars in Immunopathology 2013
Signaling pathways from the endoplasmic reticulum and their roles in disease
H Kadowaki, H Nishitoh
Genes & development 2013
Endoplasmic reticulum stress leads to lipid accumulation through upregulation of SREBP-1c in normal hepatic and hepatoma cells
D Fang, Y Wan, W Shen, J Cao, Z Sun, H Yu, Q Zhang, W Cheng, J Chen, B Ning
Molecular and Cellular Biochemistry 2013
Comparison of in vivo effects of insulin on SREBP-1c activation and INSIG-1/2 in rat liver and human and rat adipose tissue
G Boden, S Salehi, P Cheung, C Homko, W Song, C Loveland-Jones, S Jayarajan
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S Tanaka, T Yamazaki, S Asano, A Mitsumoto, D Kobayashi, N Kudo, Y Kawashima
Lipids 2013
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B Fruci, S Giuliano, A Mazza, R Malaguarnera, A Belfiore
International journal of molecular sciences 2013
Endoplasmic reticulum stress impairs cholesterol efflux and synthesis in hepatic cells
C Röhrl, K Eigner, K Winter, M Korbelius, S Obrowsky, D Kratky, WJ Kovacs, H Stangl
Journal of lipid research 2013
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C Hetz, E Chevet, HP Harding
Nature Reviews Drug Discovery 2013
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K Watanabe, E Watson, ML Cremona, EJ Millings, JH Lefkowitch, SG Fischer, CA LeDuc, RL Leibel
PloS one 2013
SIRT7 represses Myc activity to suppress ER stress and prevent fatty liver disease
J Shin, M He, Y Liu, S Paredes, L Villanova, K Brown, X Qiu, N Nabavi, M Mohrin, K Wojnoonski, P Li, HL Cheng, AJ Murphy, DM Valenzuela, H Luo, P Kapahi, R Krauss, R Mostoslavsky, GD Yancopoulos, FW Alt, KF Chua, D Chen
Cell Reports 2013
Endoplasmic reticulum is at the crossroads of autophagy, inflammation, and apoptosis signaling pathways and participates in the pathogenesis of diabetes mellitus
J Su, L Zhou, X Kong, X Yang, X Xiang, Y Zhang, X Li, L Sun
Journal of Diabetes Research 2013
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A Henkel, RM Green
Seminars in liver disease 2013
The effects of endoplasmic reticulum stress response on duck decorin stimulate myotube hypertrophy in myoblasts
L Sun, K Lu, H Liu, H Wang, X Li, C Yang, L Li, J Wang
Molecular and Cellular Biochemistry 2013
Association Between Promoter Polymorphisms of the GRP78 Gene and Risk of Type 2 Diabetes in a Chinese Han Population
S Liu, K Li, T Li, X Xiong, S Yao, Z Chen, C Wang, B Zhao
DNA and Cell Biology 2013
GRP78 overproduction in pancreatic beta cells protects against high-fat-diet-induced diabetes in mice
T Teodoro-Morrison, I Schuiki, L Zhang, DD Belsham, A Volchuk
Diabetologia 2013
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J Baumann, C Sevinsky, DS Conklin
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 2013
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DL Howarth, C Yin, K Yeh, KC Sadler
Zebrafish 2013
Proteomic analysis of liver in rats chronically exposed to fluoride
HA da Pereira, AL Leite, S Charone, JG Lobo, TM Cestari, C Peres-Buzalaf, MA Buzalaf
PloS one 2013
Transmembrane protein 208: a novel ER-localized protein that regulates autophagy and ER stress
Y Zhao, J Hu, G Miao, L Qu, Z Wang, G Li, P Lv, D Ma, Y Chen
PloS one 2013
Soluble epoxide hydrolase deficiency or inhibition attenuates diet-induced endoplasmic reticulum stress in liver and adipose tissue
A Bettaieb, N Nagata, D AbouBechara, S Chahed, C Morisseau, BD Hammock, FG Haj
The Journal of biological chemistry 2013
Association of cyclin D and estrogen receptor α36 with hepatocellular adenomas of female mice under chronic endoplasmic reticulum stress
MY Lau, H Han, J Hu, C Ji
Journal of Gastroenterology and Hepatology 2013
Activation of PPAR  Ameliorates Hepatic Insulin Resistance and Steatosis in High Fructose-Fed Mice Despite Increased Endoplasmic Reticulum Stress
SM Chan, RQ Sun, XY Zeng, ZH Choong, H Wang, MJ Watt, JM Ye
Diabetes 2013
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J Mandl, T Mészáros, G Bánhegyi, M Csala
Molecular Endocrinology 2013
Genome-Wide Association Study Identifies Novel Loci Associated With Concentrations of Four Plasma Phospholipid Fatty Acids in the De Novo Lipogenesis Pathway: Results From the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium
JH Wu, RN Lemaitre, A Manichaikul, W Guan, T Tanaka, M Foy, EK Kabagambe, L Djousse, D Siscovick, AM Fretts, C Johnson, IB King, BM Psaty, B McKnight, SS Rich, YD Chen, JA Nettleton, W Tang, S Bandinelli, DR Jacobs, BL Browning, CC Laurie, X Gu, MY Tsai, LM Steffen, L Ferrucci, M Fornage, D Mozaffarian
Circulation. Cardiovascular genetics 2013

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