Hepatic expression of FTO and fatty acid metabolic genes changes in response to lipopolysaccharide with alterations in m6A modification of relevant mRNAs in the chicken

The fat mass and obesity associated (FTO) gene, which encodes a demethylase of m(6)A, has been reported to respond to lipopolysaccharide (LPS) and to serve as a link between inflammation and metabolic responses. The objective of this study was to determine whether LPS-induced changes in the expression of FTO and metabolic genes are associated with alterations of m(6)A in relevant mRNAs.LPS challenge significantly decreased hepatic mRNA expression of carnitine palmitoyl transferase 1 (CPT1) and CPT2, which coincided with a tendency of higher triglyceride accumulation in the liver.LPS significantly down-regulated the full length cFTO1, yet up-regulated the truncated cFTO4 protein in the liver nuclear extracts.Nuclear protein content of cFTO4 in the liver was negatively correlated with the mRNA abundances of CPT1 (r=0.629) and CPT2 (r=0.622).Methylated RNA immunoprecipitation analysis revealed that the m(6)A level around the translation start site of CPT1 was markably decreased in the liver of LPS-treated chickens.These results indicate that LPS-induced changes in FTO protein expression are associated with alteration of mRNA m(6)A modification in chicken liver.