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Fructose stimulated de novo lipogenesis is promoted by inflammation
Citation
Todoric, J and Di Caro, G and Reibe, S and Henstridge, DC and Green, CR and Vrbanac, A and Ceteci, F and Conche, C and Shalapour, S and Taniguchi, K and McNulty, R and Meikle, P and Watrous, JD and Moranchel, R and Najhawan, M and Jain, M and Liu, X and Kisseleva, T and Diaz-Meco, MT and Moscat, J and Knight, R and Greten, FR and Lau, LF and Metallo, CM and Febbraio, MA and Karin, M, Fructose stimulated de novo lipogenesis is promoted by inflammation, Nature Metabolism, 2, (10) pp. 1034-1045. ISSN 2522-5812 (2020) [Refereed Article]
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DOI: 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.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | immunometabolism, liver, diabetes, cancer, gut, inflammation |
| Research Division: | Biological Sciences |
| Research Group: | Biochemistry and cell biology |
| Research Field: | Cell metabolism |
| Objective Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Clinical health not elsewhere classified |
| UTAS Author: | Henstridge, DC (Dr Darren Henstridge) |
| ID Code: | 140535 |
| Year Published: | 2020 |
| Web of Science® Times Cited: | 105 |
| Deposited By: | Health Sciences |
| Deposited On: | 2020-08-26 |
| Last Modified: | 2022-08-24 |
| Downloads: | 18 View Download Statistics |
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