| Summary: | Phosphatidylethanolamine (PE) is an important inner membrane phospholipid synthesized de novo by the CDP-ethanolamine pathway and by the decarboxylation of phosphatidylserine. CTP: phosphoethanolamine cytidylyltransferase (Pcyt2) is the main regulatory enzyme in the CDP-ethanolamine pathway and catalyzes the formation of CDP-ethanolamine from phosphoethanolamine. Complete deletion of the mouse Pcyt2 gene is embryonic lethal, and the single allele deficiency leads to development of metabolic syndrome phenotype, including liver steatosis, hypertriglyceridemia, obesity, and insulin resistance. This study aimed to specifically elucidate the effects of dietary methyl group donors betaine and choline supplementation in Pcyt2 heterozygous mice (ETKO). Evidence here shows choline and its oxidized metabolite betaine are responsible for lowering whole body weight, restoring insulin resistance, reducing hypertriglyceridemia, hepatic steatosis, and alleviating adipose and liver tissue inflammation, by restoring hepatic metabolism and gene expression. Collectively, these results establish that the impaired systemic metabolism resulting from Pcyt2 deficiency is a metabolic adaptation that is restored after methyl group supplementation.
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