Fructose stimulated de novo lipogenesis is promoted by inflammation
Todoric J, Caro G, Reibe S, Henstridge D, Green C, Vrbanac A, Ceteci F, Conche C, McNulty R, Shalapour S, Taniguchi K, Meikle P, Watrous J, Moranchel R, Najhawan M, Jain M, Liu X, Kisseleva T, Diaz-Meco M, Moscat J, Knight R, Greten F, Lau L, Metallo C, Febbraio M, Karin M (2020) Nature Metabolism Aug 24 doi: 10.1038/s42255-020-0261-2
Abstract:
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.
FAB RESEARCH COMMENT:
For the related news article please see:
Food and Behaviour Research is a registered charity (No SC034604) and a company limited by guarantee (Co No SC 253448)
Newsletter Signup
Useful Links
Contact Us
FAB Research
23 Carlton Road
Oxford
OX2 7SA
Important Notice
Medical opinion and guidance should always be sought for any symptoms that might possibly reflect a known or suspected disease, disorder or medical condition. Information provided on this website (or by FAB Research via any other means) does not in any way constitute advice on the treatment of any medical condition formally diagnosed or otherwise.
Site by Redstone Websites. Easy to Use Web Content Management. 2023 © All Rights Reserved.