The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease

Abstract

Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are the most abundant phospholipids in all mammalian cell membranes. In the 1950s, Eugene Kennedy and co-workers performed groundbreaking research that established the general outline of many of the pathways of phospholipid biosynthesis. In recent years, the importance of phospholipid metabolism in regulating lipid, lipoprotein and whole-body energy metabolism has been demonstrated in numerous dietary studies and knockout animal models. The purpose of this review is to highlight the unappreciated impact of phospholipid metabolism on health and disease. Abnormally high, and abnormally low, cellular PC/PE molar ratios in various tissues can influence energy metabolism and have been linked to disease progression. For example, inhibition of hepatic PC synthesis impairs very low density lipoprotein secretion and changes in hepatic phospholipid composition have been linked to fatty liver disease and impaired liver regeneration after surgery. The relative abundance of PC and PE regulates the size and dynamics of lipid droplets. In mitochondria, changes in the PC/PE molar ratio affect energy production. We highlight data showing that changes in the PC and/or PE content of various tissues are implicated in metabolic disorders such as atherosclerosis, insulin resistance and obesity. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.

Liver and plasma lipid changes induced by cyclic fatty acid monomers from heated vegetable oil in the rat

“…Phosphatidylcholine, phosphatidylethanolamine (PE), and the molecular ratio of PC/PE play a critical role in liver health and disease (van der Veen et al., 2017). Hepatic PC content is required both for the assembly and secretion of very low‐density lipoprotein (VLDL) and chylomicrons (Skipski et al., 1967).…”

“…Therefore, as shown in mice, PC protects against the development of steatosis (Niebergall & Vance, 2012) and a decrease in liver PC has been observed in human cases of hepatic steatosis (Puri et al., 2007). Moreover, a recent review (van der Veen et al., 2017) highlighted the importance of the cellular molar PC/PE ratio in the development of hepatic steatosis. Indeed, relatively small or larger reductions in the PC/PE molar ratio may contribute to the development of NAFLD.…”

“…In the liver, PC is biosynthesized, mainly, through the CDP‐choline pathway which is regulated by CTP: phosphocholine cytidylyltransferase (CT‐α) (Vance & Vance, 2008), and via three sequential methylations of PE by PE N ‐methyltransferase (PEMT) (Vance & Ridgway, 1988). Mice lacking hepatic CT‐α or PEMT develop nonalcoholic fatty liver disease (NAFLD), which evolves to nonalcoholic steatohepatitis, when mice are challenged with a high‐fat diet (van der Veen et al., 2017). These observations show how both pathways are critical to liver health.…”

From masochistic enzymology to mechanistic physiology and disease

“…Thus, these and other studies suggest that the PC/PE ratio is a key regulator of cell membrane integrity and that a low PC/PE ratio plays a role in the progression of steatosis (fatty liver) to steatohepatitis (fatty liver disease) (reviewed in Ref. 43). This conclusion is supported by studies showing that the molar ratio of PC to PE is a predictor of non-alcoholic fatty liver disease (NAFLD) and survival of mice after partial hepatectomy (44), suggesting that the lack of PEMT leads to non-alcoholic fatty liver disease.…”

Phospholipids and L-Carnitine Screening in Children with Congenital Heart Diseases Undergoing Surgical Correction

“…Lecithin is the most common phospholipid found in the mammalian cell. However, cephalin that is found in the surface of the mitochondria forms about 40% (9). Alterations in the cellular Lecithin / cephalin molar ratios can affect energy metabolism in different organelles, and it is related to many diseases and metabolic disorders (9).…”