Imperial College London
Alternate

Dr Toby Andrew

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 0968t.andrew

 
 
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Location

 

ICTEM 526ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Khamis:2020:10.1186/s13148-020-00858-w,
author = {Khamis, A and Boutry, R and Canouil, M and Mathew, S and Lobbens, S and Crouch, H and Andrew, T and Abderrahmani, A and Tamanini, F and Froguel, P},
doi = {10.1186/s13148-020-00858-w},
journal = {Clinical Epigenetics},
pages = {1--12},
title = {Histone deacetylase 9 promoter hypomethylation associated with adipocyte dysfunction is a statin-related metabolic effect},
url = {http://dx.doi.org/10.1186/s13148-020-00858-w},
volume = {12},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundAdipogenesis, the process whereby preadipocytes differentiate into mature adipocytes, is crucial for maintaining metabolic homeostasis. Cholesterol-lowering statins increase type 2 diabetes (T2D) risk possibly by affecting adipogenesis and insulin resistance but the (epi)genetic mechanisms involved are unknown. Here, we characterised the effects of statin treatment on adipocyte differentiation using in vitro human preadipocyte cell model to identify putative effective genes.ResultsStatin treatment during adipocyte differentiation caused a reduction in key genes involved in adipogenesis, such as ADIPOQ, GLUT4 and ABCG1. Using Illumina’s Infinium ‘850K’ Methylation EPIC array, we found a significant hypomethylation of cg14566882, located in the promoter of the histone deacetylase 9 (HDAC9) gene, in response to two types of statins (atorvastatin and mevastatin), which correlates with an increased HDAC9 mRNA expression. We confirmed that HDAC9 is a transcriptional repressor of the cholesterol efflux ABCG1 gene expression, which is epigenetically modified in obesity and prediabetic states. Thus, we assessed the putative impact of ABCG1 knockdown in mimicking the effect of statin in adipogenesis. ABCG1 KD reduced the expression of key genes involved in adipocyte differentiation and decreased insulin signalling and glucose uptake. In human blood cells from two cohorts, ABCG1 expression was impaired in response to statins, confirming that ABCG1 is targeted in vivo by these drugs.ConclusionsWe identified an epigenetic link between adipogenesis and adipose tissue insulin resistance in the context of T2D risk associated with statin use, which has important implications as HDAC9 and ABCG1 are considered potential therapeutic targets for obesity and metabolic diseases.
AU  - Khamis,A
AU  - Boutry,R
AU  - Canouil,M
AU  - Mathew,S
AU  - Lobbens,S
AU  - Crouch,H
AU  - Andrew,T
AU  - Abderrahmani,A
AU  - Tamanini,F
AU  - Froguel,P
DO  - 10.1186/s13148-020-00858-w
EP  - 12
PY  - 2020///
SN  - 1868-7083
SP  - 1
TI  - Histone deacetylase 9 promoter hypomethylation associated with adipocyte dysfunction is a statin-related metabolic effect
T2  - Clinical Epigenetics
UR  - http://dx.doi.org/10.1186/s13148-020-00858-w
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000536079700001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-020-00858-w
UR  - http://hdl.handle.net/10044/1/89600
VL  - 12
ER  -
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