Epoxygenase inactivation exacerbates diet and aging-associated metabolic dysfunction resulting from impaired adipogenesis

Olona, A and Terra, X and Ko, J-H and Grau-Bové, C and Pinent, M and Ardevol, A and Diaz, A G and Moreno-Moral, A and Edin, M and Bishop-Bailey, D and Zeldin, D C and Aitman, T J and Petretto, E and Blay, M and Behmoaras, J (2018) Epoxygenase inactivation exacerbates diet and aging-associated metabolic dysfunction resulting from impaired adipogenesis. Molecular Metabolism, 11. pp. 18-32.

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Abstract

• Cyp2j4 deletion in rats offers a simplified genetic landscape as opposed to the mice locus, which is under significant allelic expansion. • Under different metabolic stresses (aging, cafeteria diet), Cyp2j4−/− rats show an accelerated adipogenesis, which progress towards adipocyte dysfunction. • Adipocyte dysfunction in Cyp2j4−/− rats under cafeteria diet (CAF) is characterised by down-regulation of white adipose tissue (WAT) PPARγ and C/EBPα, adipocyte hypertrophy and extracellular matrix remodeling. • Cyp2j4−/− rats treated with CAF display exacerbated weight gain, insulin resistance, hepatic lipid accumulation and dysregulated gluconeogenesis. • Cyp2j4−/− rats display alternative arachidonic acid pathway usage in their adipose tissue upon CAF and aging.