The Tp53 gene is a well-known tumour suppressor, mutation of which (e.g. prevention of Ser312 phosphorylation) induces deletion or expression of an inactive p53 protein to increase the susceptibility of tumour occurance. However, the role of Tp53 gene in maintaining metabolic homeostasis for regulating physio-pathological activities is still not well-understood. This study aimed to use the lipidomics study as a systematic approach to understand the relationship between the phenotypic effects of Tp53 mutation on lipid-related endogenous metabolites. Plasma and liver samples from mice carrying a Tp53 Ser312 to Ala mutation and wild type mice were collected, lipids were extracted by liquid-liquid extraction method and analyzed by the RPLC-LTQ-FTMS for the lipidomics study. Our results indicated that defect in Ser312 phosphorylation of Tp53 leads the lipid disturbance (e.g. triacylglycerols) for fatty accumulation and fatty liver susceptibility, which is with preference of females. Histological observation by staining with haematoxylin and eosin further validated our lipidomics findings. To our conclusion, fatty liver occurrence may have different phenotypes, one of which is strongly linked with the Tp53 mutation and is susceptible in females. Lipidomics as a technique to detect a great number of endogenous compounds provides precise metabolic information that may further help improve personalized diagnosis of Chronic hepatic diseases.
Keywords: Lipidomics; Liver; Plasma; Sex-Related fatty accumulation and fatty liver susceptibility; Tp53 mutation.
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