PhosphatidylethanolamineN‐methyltransferase(PEMT)gene expression is induced by estrogen in human and mouse primary hepatocytes

Abstract

Choline is an essential nutrient for humans, though some of the requirement can be met by endogenous synthesis catalyzed by phosphatidylethanolamine N-methyltransferase (PEMT). Premenopausal women are relatively resistant to choline deficiency compared with postmenopausal women and men. Studies in animals suggest that estrogen treatment can increase PEMT activity. In this study we investigated whether the PEMT gene is regulated by estrogen. PEMT transcription was increased in a dose-dependent manner when primary mouse and human hepatocytes were treated with 17-beta-estradiol for 24 h. This increased message was associated with an increase in protein expression and enzyme activity. In addition, we report a region that contains a perfect estrogen response element (ERE) approximately 7.5 kb from the transcription start site corresponding to transcript variants NM_007169 and NM-008819 of the human and murine PEMT genes, respectively, three imperfect EREs in evolutionarily conserved regions and multiple imperfect EREs in nonconserved regions in the putative promoter regions. We predict that both the mouse and human PEMT genes have three unique transcription start sites, which are indicative of either multiple promoters and/or alternative splicing. This study is the first to explore the underlying mechanism of why dietary requirements for choline vary with estrogen status in humans.

Estrogen Receptor α Promotes Breast Cancer by Reprogramming Choline Metabolism

“…Abnormally high synthesis of PtdCho via the cytidine diphosphate-choline (CDP-Cho) pathway, where CTP:phosphocholine cytidylyltransferase (CCT) has been identified as the rate-limiting enzyme, is generally recognized as a metabolic hallmark of cancer (18,19). PtdCho can also be synthesized through 5 methylation of phosphatidylethanolamine (PE) by phosphatidylethanolamine Nmethyltransferase (PEMT) (20). The PEMT gene has been shown to be induced by estrogen in hepatocytes (20).…”

“…PtdCho can also be synthesized through 5 methylation of phosphatidylethanolamine (PE) by phosphatidylethanolamine Nmethyltransferase (PEMT) (20). The PEMT gene has been shown to be induced by estrogen in hepatocytes (20).…”

Serum Choline Plasmalogen is a Reliable Biomarker for Atherogenic Status

“…This observation also suggests the importance of PlsCho in the transport of TG from liver, and the participation of the lack of PlsCho in the onset of metabolic syndrome (MetS), because NAFLD shares many features of the MetS, such as abdominal obesity, type 2 diabetes, dyslipidemia, and insulin resistance (Pacifico et al, 2011). Human PEMT gene is regulated by estrogen (Resseguie et al, 2007), which may explain the sex difference in serum levels of PlsCho, despite no significant sex difference in serum levels of PC, and provide an evidence supporting the involvement of PEMT pathway in the synthesis of PlsCho. Moreover, a nutritional insufficiency in the methyl donor such as methionine or choline also causes lack of PlsCho and elevated homocysteine (Hcy), a risk factor for cardiovascular disease.…”

Loss of intracellular lipid binding proteins differentially impacts saturated fatty acid uptake and nuclear targeting in mouse hepatocytes

“…Isolated hepatocytes were plated on collagen-coated six-well culture plates at a density of 1 ϫ 10 6 cells/well, cultured overnight in DMEM-F12 medium (57,58,72), rinsed twice with PBS, and cultured in glucose-free DMEM (1 ml/well) supplemented with 6 or 20 mM glucose for 0, 1, 2, or 6 h (n ϭ 3 wells per medium type per time point). For radiolabeled experiments, 1 l of [ 3 H]glucose was added to 13 ml of the 6 mM medium (5,171 cpm/mol glucose), and 1 l of [ 3 H]glucose was added to 13 ml of the 20 mM medium (1,551 cpm/mol glucose).…”