Imperial College London
Alternate

ProfessorStuartCook

Faculty of Medicine, Institute of Clinical Sciences

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 3313 1346stuart.cook

 
 
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Location

 

RF 16Sydney StreetRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Zhou:2022:10.1038/s41467-022-32788-x,
author = {Zhou, J and Pang, J and Tripathi, M and Ho, JP and Widjaja, AA and Shekeran, SG and Cook, SA and Suzuki, A and Diehl, AM and Petretto, E and Singh, BK and Yen, PM},
doi = {10.1038/s41467-022-32788-x},
journal = {Nature Communications},
pages = {1--14},
title = {Spermidine-mediated hypusination of translation factor EIF5A improves mitochondrial fatty acid oxidation and prevents non-alcoholic steatohepatitis progression},
url = {http://dx.doi.org/10.1038/s41467-022-32788-x},
volume = {13},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Spermidine is a natural polyamine that has health benefits and extends life span in several species. Deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH) are key enzymes that utilize spermidine to catalyze the post-translational hypusination of the translation factor EIF5A (EIF5AH). Here, we have found that hepatic DOHH mRNA expression is decreased in patients and mice with non-alcoholic steatohepatitis (NASH), and hepatic cells treated with fatty acids. The mouse and cell culture models of NASH have concomitant decreases in Eif5aH and mitochondrial protein synthesis which leads to lower mitochondrial activity and fatty acid β-oxidation. Spermidine treatment restores EIF5AH, partially restores protein synthesis and mitochondrial function in NASH, and prevents NASH progression in vivo. Thus, the disrupted DHPS-DOHH-EIF5AH pathway during NASH represents a therapeutic target to increase hepatic protein synthesis and mitochondrial fatty acid oxidation (FAO) and prevent NASH progression.
AU  - Zhou,J
AU  - Pang,J
AU  - Tripathi,M
AU  - Ho,JP
AU  - Widjaja,AA
AU  - Shekeran,SG
AU  - Cook,SA
AU  - Suzuki,A
AU  - Diehl,AM
AU  - Petretto,E
AU  - Singh,BK
AU  - Yen,PM
DO  - 10.1038/s41467-022-32788-x
EP  - 14
PY  - 2022///
SN  - 2041-1723
SP  - 1
TI  - Spermidine-mediated hypusination of translation factor EIF5A improves mitochondrial fatty acid oxidation and prevents non-alcoholic steatohepatitis progression
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-022-32788-x
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000849494300008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/s41467-022-32788-x
UR  - http://hdl.handle.net/10044/1/100773
VL  - 13
ER  -
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