Impact of fish oil on epigenetic regulation in perirenal adipose tissue of obese mice

Abstract

It has been demonstrated that fish oil (FO), a source of omega-3 polyunsaturated fatty acids (n-3 PUFA), offers partial protection to mice from the adverse effects of a high-fat diet (HFD) by altering the expression of genes involved in adipogenesis and adipocyte metabolism. Histone 3 lysine 27 (H3K27) modifiers, namely Ezh2, Kdm6a, Kdm6b, Crebbp and Ep300, are vital for the appropriate differentiation and metabolism of adipocytes, as they can either silence or activate transcription. The expansion of perirenal adipose tissue (AT) in obesity is associated with a number of complications, including hypertension and kidney disease. The aim of this study was to assess the expression of H3K27 modifiers and genes involved in adipogenesis and adipocyte metabolism in perirenal AT of HFD-fed and FO-treated (5DHA:1EPA) mice using real-time PCR. This study demonstrates, for the first time, that a high-fat diet (HFD) increases the expression of Kdm6b (H3K27 demethylase) in perirenal AT, and that treatment with FO can completely reverse this effect. Conversely, the expression of the Acly gene, which encodes an enzyme that provides a substrate for histone acetylases, was found to be reduced in HFD-fed mice and this was not reversed by FO treatment. Additionally, transcription factor genes, such as Tbx1, exhibited diminished expression in perirenal AT of mice fed an HFD. These observations suggest that a HFD affects the expression of chromatin modifiers, transcription factors, and metabolic genes in perirenal AT, and that FO can reverse some of these effects, offering a promising avenue for the treatment of obesity.

Keywords: Epigenetics; H3K27; Kdm6b, high-fat diet; Omega−3 fatty acids; Perirenal adipose tissue.