Imperial College London
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DrVikashReebye

Faculty of Medicine, Department of Surgery & Cancer

Research Fellow in Gene Activation
 
 
 
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Contact

 

+44 (0)20 3313 2047v.reebye

 
 
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Location

 

B BlockHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Huang:2020:10.1016/j.omtn.2019.10.044,
author = {Huang, K-W and Reebye, V and Czysz, K and Ciriello, S and Dorman, S and Reccia, I and Lai, H-S and Peng, L and Kostomitsopoulos, N and Nicholls, J and Habib, RS and Tomalia, DA and Saetrom, P and Wilkes, E and Cutillas, P and Rossi, JJ and Habib, NA},
doi = {10.1016/j.omtn.2019.10.044},
journal = {Molecular Therapy : Nucleic Acids},
pages = {361--370},
title = {Liver activation of hepatocellular nuclear factor-4 alpha by small activating RNA rescues dyslipidemia and improves metabolic profile},
url = {http://dx.doi.org/10.1016/j.omtn.2019.10.044},
volume = {19},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Non-alcoholic fatty liver disease (NAFLD) culminates in insulin resistance and metabolic syndrome. Because there are no approved pharmacological treatment agents for non-alcoholic steatohepatitis (NASH) and NAFLD, different signaling pathways are under investigation for drug development with the focus on metabolic pathways. Hepatocyte nuclear factor 4-alpha (HNF4A) is at the center of a complex transcriptional network where its disruption is directly linked to glucose and lipid metabolism. Resetting HNF4A expression in NAFLD is therefore crucial for re-establishing normal liver function. Here, small activating RNA (saRNA) specific for upregulating HNF4A was injected into rats fed a high-fat diet for 16 weeks. Intravenous delivery was carried out using 5-(G5)-triethanolamine-core polyamidoamine (PAMAM) dendrimers. We observed a significant reduction in liver triglyceride, increased high-density lipoprotein/low-density lipoprotein (HDL/LDL) ratio, and decreased white adipose tissue/body weight ratio, all parameters to suggest that HNF4A-saRNA treatment induced a favorable metabolic profile. Proteomic analysis showed significant regulation of genes involved in sphingolipid metabolism, fatty acid β-oxidation, ketogenesis, detoxification of reactive oxygen species, and lipid transport. We demonstrate that HNF4A activation by oligonucleotide therapy may represent a novel single agent for the treatment of NAFLD and insulin resistance.
AU  - Huang,K-W
AU  - Reebye,V
AU  - Czysz,K
AU  - Ciriello,S
AU  - Dorman,S
AU  - Reccia,I
AU  - Lai,H-S
AU  - Peng,L
AU  - Kostomitsopoulos,N
AU  - Nicholls,J
AU  - Habib,RS
AU  - Tomalia,DA
AU  - Saetrom,P
AU  - Wilkes,E
AU  - Cutillas,P
AU  - Rossi,JJ
AU  - Habib,NA
DO  - 10.1016/j.omtn.2019.10.044
EP  - 370
PY  - 2020///
SN  - 2162-2531
SP  - 361
TI  - Liver activation of hepatocellular nuclear factor-4 alpha by small activating RNA rescues dyslipidemia and improves metabolic profile
T2  - Molecular Therapy : Nucleic Acids
UR  - http://dx.doi.org/10.1016/j.omtn.2019.10.044
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000519557700032&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.sciencedirect.com/science/article/pii/S2162253119303671?via%3Dihub
UR  - http://hdl.handle.net/10044/1/83474
VL  - 19
ER  -
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