Imperial College London
Portrait Picture

Professor Marc-Emmanuel Dumas

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Chair in Systems Medicine
 
 
 
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Contact

 

+44 (0)20 7594 1820m.dumas Website

 
 
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Assistant

 

Mrs Patricia Murphy +44 (0)20 7594 1603

 
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Location

 

E315BBurlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Menghini:2022:10.1016/j.molmet.2022.101454,
author = {Menghini, R and Hoyles, L and Cardellini, M and Casagrande, V and Marino, A and Gentileschi, P and Davato, F and Mavilio, M and Arisi, I and Mauriello, A and Montanaro, M and Scimeca, M and Barton, RH and Rappa, F and Cappello, F and Vinciguerra, M and Moreno-Navarrete, JM and Ricart, W and Porzio, O and Fernandez-Real, J-M and Burcelin, R and Dumas, M-E and Federici, M},
doi = {10.1016/j.molmet.2022.101454},
journal = {Molecular Metabolism},
title = {ITCH E3 ubiquitin ligase downregulation compromises hepatic degradation of branched-chain amino acids},
url = {http://dx.doi.org/10.1016/j.molmet.2022.101454},
volume = {59},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - ObjectiveMetabolic syndrome, obesity, and steatosis are characterized by a range of dysregulations including defects in ubiquitin ligase tagging proteins for degradation. The identification of novel hepatic genes associated with fatty liver disease and metabolic dysregulation may be relevant to unravelling new mechanisms involved in liver disease progressionMethodsThrough integrative analysis of liver transcriptomic and metabolomic obtained from obese subjects with steatosis, we identified itchy E ubiquitin protein ligase (ITCH) as a gene downregulated in human hepatic tissue in relation to steatosis grade. Wild-type or ITCH knockout mouse models of non-alcoholic fatty liver disease (NAFLD) and obesity-related hepatocellular carcinoma were analyzed to dissect the causal role of ITCH in steatosisResultsWe show that ITCH regulation of branched-chain amino acids (BCAAs) degradation enzymes is impaired in obese women with grade 3 compared with grade 0 steatosis, and that ITCH acts as a gatekeeper whose loss results in elevation of circulating BCAAs associated with hepatic steatosis. When ITCH expression was specifically restored in the liver of ITCH knockout mice, ACADSB mRNA and protein are restored, and BCAA levels are normalized both in liver and plasmaConclusionsOur data support a novel functional role for ITCH in the hepatic regulation of BCAA metabolism and suggest that targeting ITCH in a liver-specific manner might help delay the progression of metabolic hepatic diseases and insulin resistance.
AU  - Menghini,R
AU  - Hoyles,L
AU  - Cardellini,M
AU  - Casagrande,V
AU  - Marino,A
AU  - Gentileschi,P
AU  - Davato,F
AU  - Mavilio,M
AU  - Arisi,I
AU  - Mauriello,A
AU  - Montanaro,M
AU  - Scimeca,M
AU  - Barton,RH
AU  - Rappa,F
AU  - Cappello,F
AU  - Vinciguerra,M
AU  - Moreno-Navarrete,JM
AU  - Ricart,W
AU  - Porzio,O
AU  - Fernandez-Real,J-M
AU  - Burcelin,R
AU  - Dumas,M-E
AU  - Federici,M
DO  - 10.1016/j.molmet.2022.101454
PY  - 2022///
SN  - 2212-8778
TI  - ITCH E3 ubiquitin ligase downregulation compromises hepatic degradation of branched-chain amino acids
T2  - Molecular Metabolism
UR  - http://dx.doi.org/10.1016/j.molmet.2022.101454
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000794064300009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR  - https://www.sciencedirect.com/science/article/pii/S2212877822000230
UR  - http://hdl.handle.net/10044/1/109711
VL  - 59
ER  -
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