Epigenome-wide methylation analysis shows phosphonoethylamine alleviates aberrant DNA methylation in NASH caused by Pcyt2 deficiency.

Sophie Grapentine, Prasoon Agarwal, Vernon W Dolinsky, Marica Bakovic

Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Canada.Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Canada. · pubmed

Paper

Abstract

Aberrant DNA methylation can lead to the onset of pathological phenotypes and is increasingly being implicated in age-related metabolic diseases. In our preceding study we show that the heterozygous ablation of Pcyt2, the rate limiting enzyme in phosphatidylethanolamine (PE) synthesis, causes an age-dependent development of non-alcoholic steatohepatitis (NASH), and that treatment with the Pcyt2 substrate phosphonoethylamine (PEA) can attenuate phenotypic NASH pathologies. Here, we hypothesize that abnormal DNA methylation patterns underly the development of Pcyt2 + /- NASH. In this study, we conduct an epigenome-wide methylation analysis to characterize the differential methylation of Pcyt2 + /- livers and investigate whether the attenuation of NASH with PEA treatment is associated with changes in DNA methylation.

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Research summary

The paper claims that phosphonoethylamine treatment can alleviate aberrant DNA methylation associated with NASH due to Pcyt2 deficiency. This research addresses the underlying mechanisms of DNA methylation in the context of an age-related metabolic disease, which is relevant to understanding and potentially mitigating aspects of aging.

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