Imperial College London
Alternate

DrJacquesBehmoaras

Faculty of Medicine, Department of Immunology and Inflammation

Reader in Immunogenetics
 
 
 
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Contact

 

+44 (0)20 3313 2339jacques.behmoaras Website

 
 
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Location

 

9N13Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Olona:2018:10.1016/j.molmet.2018.03.003,
author = {Olona, A and Terra, X and Ko, JH and Grau-Bove, C and Pinent, M and Ardevol, A and Garcia, Diaz A and Moreno-Moral, A and Edin, M and Bishop-Bailey, D and Zeldin, DC and Aitman, TJ and Petretto, E and Blay, M and Behmoaras, JV},
doi = {10.1016/j.molmet.2018.03.003},
journal = {Molecular Metabolism},
pages = {18--32},
title = {Epoxygenase inactivation exacerbates diet and aging-associated metabolic dysfunction resulting from impaired adipogenesis},
url = {http://dx.doi.org/10.1016/j.molmet.2018.03.003},
volume = {11},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Objective: When molecular drivers of healthy adipogenesis are perturbed, this can cause hepatic steatosis. The role of arachidonic acid (AA) and its downstream enzymatic cascades such as cyclooxygenase in adipogenesis is well established while the exact contribution of P450 epoxygenase pathway remain to be established. Enzymes belonging to this pathway are mainly encoded by theCYP2J locus but the latter shows extensive allelic expansion in mice, an obstacle for adipogenesis-related studies. The human CYP2J locus contains a single gene (CYP2J2) whereas mice and rats have 8 and 3 paralogues, respectively.Methods and results: We took advantage of the simpler genetic architecture of the Cyp2jlocus in the rat and generated a Cyp2j4 (orthologue of human CYP2J2) knockout rat. We used Cyp2j4-/- rats in two models of metabolic dysfunction: physiological aging and cafeteria diet (CAF). The phenotyping of Cyp2j4-/- rats under CAF was integrated with proteomics (LC-MS/MS) and lipidomics (LC-MS) analyses in the liver and the adipose tissue. We report that Cyp2j4 deletion causes adipocyte dysfunction under metabolic challenges. This is characterised by (i) down-regulation of white adipose tissue (WAT) PPARγ and C/EBPα, (ii) adipocyte hypertrophy (iii) extracellular matrix remodelling and (iv) alternative usage of AA pathway. Specifically, in Cyp2j4-/- rats treated with a cafeteria diet, the dysfunctional adipogenesis is accompanied by exacerbated weight gain, hepatic lipid accumulation and dysregulated gluconeogenesis.  Conclusion: These results suggest that AA epoxygenases are essential regulators of healthy adipogenesis. Our results uncover their synergistic role in fine-tuning AA pathway in obesity-mediated hepatic steatosis.
AU  - Olona,A
AU  - Terra,X
AU  - Ko,JH
AU  - Grau-Bove,C
AU  - Pinent,M
AU  - Ardevol,A
AU  - Garcia,Diaz A
AU  - Moreno-Moral,A
AU  - Edin,M
AU  - Bishop-Bailey,D
AU  - Zeldin,DC
AU  - Aitman,TJ
AU  - Petretto,E
AU  - Blay,M
AU  - Behmoaras,JV
DO  - 10.1016/j.molmet.2018.03.003
EP  - 32
PY  - 2018///
SN  - 2212-8778
SP  - 18
TI  - Epoxygenase inactivation exacerbates diet and aging-associated metabolic dysfunction resulting from impaired adipogenesis
T2  - Molecular Metabolism
UR  - http://dx.doi.org/10.1016/j.molmet.2018.03.003
UR  - http://hdl.handle.net/10044/1/57854
VL  - 11
ER  -
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