Implication of phosphatidylethanolamine N-methyltransferase in adipocyte differentiation.

Abstract

Phosphatidylethanolamine N-methyltransferase (PEMT) is a small integral membrane protein that converts phosphatidylethanolamine (PE) into phosphatidylcholine (PC). It has been previously reported that, unexpectedly, PEMT deficiency protected from high-fat diet (HFD)-induced obesity and insulin resistance, pointing to a possible role of this enzyme in the regulation of adipose cell metabolism. Using mouse 3T3-L1 preadipocytes as a biological system, we demonstrate that PEMT expression is strongly increased during the differentiation of preadipocytes into mature adipose cells. Knockdown of PEMT reduced the expression of early and late adipogenic markers, inhibited lipid droplet formation, reduced triacylglycerol content and decreased the levels of leptin release from the adipocytes, suggesting that PEMT is a novel and relevant regulator of adipogenesis. Investigation into the mechanisms whereby PEMT regulates adipocyte differentiation revealed that extracellularly regulated kinases (ERK1/2) and AKT are essential factors in this process. Specifically, the activities of ERK1/2 and AKT, which are decreased during adipocyte differentiation, were elevated upon Pemt knockdown. Moreover, treatment of cells with exogenous ceramide 1-phosphate (C1P), which we reported to be a negative regulator of adipogenesis, decreased PEMT expression, suggesting that PEMT is also a relevant factor in the anti-adipogenic action of C1P. Altogether, the data presented here identify PEMT as a novel regulator of adipogenesis and a mediator of the anti-adipogenic action of C1P.

• Authors: Natalia Presa, Asier Dominguez-Herrera, Jelske N van der Veen, Dennis E Vance, Antonio Gómez-Muñoz
• Journal: Biochimica et biophysica acta. Molecular basis of disease (Biochim Biophys Acta Mol Basis Dis) Vol. 1866 Issue 10 Pg. 165853 (10 01 2020) ISSN: 1879-260X [Electronic] Netherlands
• PMID: 32502648 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Ceramides
• Culture Media
• RNA, Small Interfering
• ceramide 1-phosphate
• PEMT protein, mouse
• Phosphatidylethanolamine N-Methyltransferase
• Akt1 protein, mouse
• Proto-Oncogene Proteins c-akt
• Mapk1 protein, mouse
• Mapk3 protein, mouse
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3

Topics

• 3T3-L1 Cells
• Adipocytes (physiology)
• Adipogenesis (physiology)
• Animals
• Cell Differentiation (physiology)
• Ceramides (metabolism)
• Culture Media (metabolism)
• Gene Knockdown Techniques
• Lipid Droplets (metabolism)
• Mice
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Phosphatidylethanolamine N-Methyltransferase (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA, Small Interfering (metabolism)
• Signal Transduction
• Up-Regulation