-transparent.png){kind=logo}
Fructose stimulated de novo lipogenesis is promoted by inflammation. 2020
Jelena Todoric, and
Giuseppe Di Caro, and
Saskia Reibe, and
Darren C Henstridge, and
Courtney R Green, and
Alison Vrbanac, and
Fatih Ceteci, and
Claire Conche, and
Reginald McNulty, and
Shabnam Shalapour, and
Koji Taniguchi, and
Peter J Meikle, and
Jeramie D Watrous, and
Rafael Moranchel, and
Mahan Najhawan, and
Mohit Jain, and
Xiao Liu, and
Tatiana Kisseleva, and
Maria T Diaz-Meco, and
Jorge Moscat, and
Rob Knight, and
Florian R Greten, and
Lester F Lau, and
Christian M Metallo, and
Mark A Febbraio, and
Michael Karin
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Benign hepatosteatosis, affected by lipid uptake, de novo lipogenesis and fatty acid (FA) oxidation, progresses to non-alcoholic steatohepatitis (NASH) on stress and inflammation. A key macronutrient proposed to increase hepatosteatosis and NASH risk is fructose. Excessive intake of fructose causes intestinal-barrier deterioration and endotoxaemia. However, how fructose triggers these alterations and their roles in hepatosteatosis and NASH pathogenesis remain unknown. Here we show, using mice, that microbiota-derived Toll-like receptor (TLR) agonists promote hepatosteatosis without affecting fructose-1-phosphate (F1P) and cytosolic acetyl-CoA. Activation of mucosal-regenerative gp130 signalling, administration of the YAP-induced matricellular protein CCN1 or expression of the antimicrobial peptide Reg3b (beta) peptide counteract fructose-induced barrier deterioration, which depends on endoplasmic-reticulum stress and subsequent endotoxaemia. Endotoxin engages TLR4 to trigger TNF production by liver macrophages, thereby inducing lipogenic enzymes that convert F1P and acetyl-CoA to FA in both mouse and human hepatocytes.
Related Publications
Jelena Todoric, and
Giuseppe Di Caro, and
Saskia Reibe, and
Darren C Henstridge, and
Courtney R Green, and
Alison Vrbanac, and
Fatih Ceteci, and
Claire Conche, and
Reginald McNulty, and
Shabnam Shalapour, and
Koji Taniguchi, and
Peter J Meikle, and
Jeramie D Watrous, and
Rafael Moranchel, and
Mahan Najhawan, and
Mohit Jain, and
Xiao Liu, and
Tatiana Kisseleva, and
Maria T Diaz-Meco, and
Jorge Moscat, and
Rob Knight, and
Florian R Greten, and
Lester F Lau, and
Christian M Metallo, and
Mark A Febbraio, and
Michael Karin
May 2023,
The Journal of endocrinology,
Jelena Todoric, and
Giuseppe Di Caro, and
Saskia Reibe, and
Darren C Henstridge, and
Courtney R Green, and
Alison Vrbanac, and
Fatih Ceteci, and
Claire Conche, and
Reginald McNulty, and
Shabnam Shalapour, and
Koji Taniguchi, and
Peter J Meikle, and
Jeramie D Watrous, and
Rafael Moranchel, and
Mahan Najhawan, and
Mohit Jain, and
Xiao Liu, and
Tatiana Kisseleva, and
Maria T Diaz-Meco, and
Jorge Moscat, and
Rob Knight, and
Florian R Greten, and
Lester F Lau, and
Christian M Metallo, and
Mark A Febbraio, and
Michael Karin
January 2017,
Gene regulation and systems biology,
Jelena Todoric, and
Giuseppe Di Caro, and
Saskia Reibe, and
Darren C Henstridge, and
Courtney R Green, and
Alison Vrbanac, and
Fatih Ceteci, and
Claire Conche, and
Reginald McNulty, and
Shabnam Shalapour, and
Koji Taniguchi, and
Peter J Meikle, and
Jeramie D Watrous, and
Rafael Moranchel, and
Mahan Najhawan, and
Mohit Jain, and
Xiao Liu, and
Tatiana Kisseleva, and
Maria T Diaz-Meco, and
Jorge Moscat, and
Rob Knight, and
Florian R Greten, and
Lester F Lau, and
Christian M Metallo, and
Mark A Febbraio, and
Michael Karin
May 2005,
Cancer cell,
Jelena Todoric, and
Giuseppe Di Caro, and
Saskia Reibe, and
Darren C Henstridge, and
Courtney R Green, and
Alison Vrbanac, and
Fatih Ceteci, and
Claire Conche, and
Reginald McNulty, and
Shabnam Shalapour, and
Koji Taniguchi, and
Peter J Meikle, and
Jeramie D Watrous, and
Rafael Moranchel, and
Mahan Najhawan, and
Mohit Jain, and
Xiao Liu, and
Tatiana Kisseleva, and
Maria T Diaz-Meco, and
Jorge Moscat, and
Rob Knight, and
Florian R Greten, and
Lester F Lau, and
Christian M Metallo, and
Mark A Febbraio, and
Michael Karin
September 2018,
Nutrients,
Jelena Todoric, and
Giuseppe Di Caro, and
Saskia Reibe, and
Darren C Henstridge, and
Courtney R Green, and
Alison Vrbanac, and
Fatih Ceteci, and
Claire Conche, and
Reginald McNulty, and
Shabnam Shalapour, and
Koji Taniguchi, and
Peter J Meikle, and
Jeramie D Watrous, and
Rafael Moranchel, and
Mahan Najhawan, and
Mohit Jain, and
Xiao Liu, and
Tatiana Kisseleva, and
Maria T Diaz-Meco, and
Jorge Moscat, and
Rob Knight, and
Florian R Greten, and
Lester F Lau, and
Christian M Metallo, and
Mark A Febbraio, and
Michael Karin
August 2001,
The British journal of nutrition,
Jelena Todoric, and
Giuseppe Di Caro, and
Saskia Reibe, and
Darren C Henstridge, and
Courtney R Green, and
Alison Vrbanac, and
Fatih Ceteci, and
Claire Conche, and
Reginald McNulty, and
Shabnam Shalapour, and
Koji Taniguchi, and
Peter J Meikle, and
Jeramie D Watrous, and
Rafael Moranchel, and
Mahan Najhawan, and
Mohit Jain, and
Xiao Liu, and
Tatiana Kisseleva, and
Maria T Diaz-Meco, and
Jorge Moscat, and
Rob Knight, and
Florian R Greten, and
Lester F Lau, and
Christian M Metallo, and
Mark A Febbraio, and
Michael Karin
April 2014,
The Journal of biological chemistry,
Jelena Todoric, and
Giuseppe Di Caro, and
Saskia Reibe, and
Darren C Henstridge, and
Courtney R Green, and
Alison Vrbanac, and
Fatih Ceteci, and
Claire Conche, and
Reginald McNulty, and
Shabnam Shalapour, and
Koji Taniguchi, and
Peter J Meikle, and
Jeramie D Watrous, and
Rafael Moranchel, and
Mahan Najhawan, and
Mohit Jain, and
Xiao Liu, and
Tatiana Kisseleva, and
Maria T Diaz-Meco, and
Jorge Moscat, and
Rob Knight, and
Florian R Greten, and
Lester F Lau, and
Christian M Metallo, and
Mark A Febbraio, and
Michael Karin
July 2016,
World journal of hepatology,
Jelena Todoric, and
Giuseppe Di Caro, and
Saskia Reibe, and
Darren C Henstridge, and
Courtney R Green, and
Alison Vrbanac, and
Fatih Ceteci, and
Claire Conche, and
Reginald McNulty, and
Shabnam Shalapour, and
Koji Taniguchi, and
Peter J Meikle, and
Jeramie D Watrous, and
Rafael Moranchel, and
Mahan Najhawan, and
Mohit Jain, and
Xiao Liu, and
Tatiana Kisseleva, and
Maria T Diaz-Meco, and
Jorge Moscat, and
Rob Knight, and
Florian R Greten, and
Lester F Lau, and
Christian M Metallo, and
Mark A Febbraio, and
Michael Karin
May 2016,
Digestive diseases and sciences,
Jelena Todoric, and
Giuseppe Di Caro, and
Saskia Reibe, and
Darren C Henstridge, and
Courtney R Green, and
Alison Vrbanac, and
Fatih Ceteci, and
Claire Conche, and
Reginald McNulty, and
Shabnam Shalapour, and
Koji Taniguchi, and
Peter J Meikle, and
Jeramie D Watrous, and
Rafael Moranchel, and
Mahan Najhawan, and
Mohit Jain, and
Xiao Liu, and
Tatiana Kisseleva, and
Maria T Diaz-Meco, and
Jorge Moscat, and
Rob Knight, and
Florian R Greten, and
Lester F Lau, and
Christian M Metallo, and
Mark A Febbraio, and
Michael Karin
March 2014,
European journal of pharmacology,
Jelena Todoric, and
Giuseppe Di Caro, and
Saskia Reibe, and
Darren C Henstridge, and
Courtney R Green, and
Alison Vrbanac, and
Fatih Ceteci, and
Claire Conche, and
Reginald McNulty, and
Shabnam Shalapour, and
Koji Taniguchi, and
Peter J Meikle, and
Jeramie D Watrous, and
Rafael Moranchel, and
Mahan Najhawan, and
Mohit Jain, and
Xiao Liu, and
Tatiana Kisseleva, and
Maria T Diaz-Meco, and
Jorge Moscat, and
Rob Knight, and
Florian R Greten, and
Lester F Lau, and
Christian M Metallo, and
Mark A Febbraio, and
Michael Karin
February 2020,
Nature communications,
