Journal article

Fructose stimulated de novo lipogenesis is promoted by inflammation

Jelena Todoric, Giuseppe Di Caro, Saskia Reibe, Darren C Henstridge, Courtney R Green, Alison Vrbanac, Fatih Ceteci, Claire Conche, Reginald McNulty, Shabnam Shalapour, Koji Taniguchi, Peter J Meikle, Jeramie D Watrous, Rafael Moranchel, Mahan Najhawan, Mohit Jain, Xiao Liu, Tatiana Kisseleva, Maria T Diaz-Meco, Jorge Moscat Show all

Nature Metabolism | NATURE RESEARCH | Published : 2020


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 signall..

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University of Melbourne Researchers


Awarded by NIH


Awarded by Australian NHMRC

Awarded by LOEWE Center Frankfurt Cancer Institute (FCI) - Hessen State Ministry for Higher Education, Research and the Arts

Awarded by NHMRC Australia

Funding Acknowledgements

We thank M. Raffatellu for advice and discussion and V. Sheen, W. Gong, J. Yung and K. Lam for technical support. Research was supported by grants from the NIH (P42ES010337, R01DK120714, R01CA198103, R01AI043477, R01CA211794 and R01CA234128 to M.K.; R03CA223717 to J.T.; T32AI007469 and K22AI139444 to R.MN..; R01CA192642, R01CA218254 to M.T.D.-M.; R01DK108743, R01CA207177 and R01CA211794 to J.M.; U01AA027681 to S.S. and M.K.; and R01CA188652 to C.M.M.), JSPS KAKENHI (JP15K21775) and 'Kibou Projects' Startup Support for Young Researchers in Immunology (to K.T.), and the Australian NHMRC (APP112227) to M.A.F. and M.K.; work in F.R.G.'s laboratory was supported by institutional funds from the Georg-Speyer-Haus and by the LOEWE Center Frankfurt Cancer Institute (FCI), funded by the Hessen State Ministry for Higher Education, Research and the Arts (III L 5 - 519/03/03.001 - (0015)), NIH K01DK116917 and P30DK063491 pilot award to J.D.W.; and S10OD020025, R01ES027595, and P42ES010337 to M.J. M.A.F. is a senior principal research fellow of the NHMRC Australia (APP 1116936).