Phosphatidylcholine Metabolism in Hepatic Disorders

Phosphatidylcholine, the most abundant phospholipid of hepatocyte membranes, is central to lipid transport, membrane integrity and methyl group metabolism in the liver. Hepatic disorders such as nonalcoholic fatty liver disease and steatohepatitis often exhibit dysregulated phosphatidylcholine homeostasis, with altered de novo synthesis via the CDP-choline pathway and the phosphatidylethanolamine N-methyltransferase pathway contributing to lipid accumulation, impaired very low-density lipoprotein secretion and disrupted methionine cycle flux. Emerging evidence has highlighted additional mechanisms sustaining hepatic phosphatidylcholine pools, including uptake of circulating lysophosphatidylcholine and regulated catabolism of membrane phosphatidylcholine to supply choline for methylation reactions. Disturbances in these pathways can exacerbate oxidative stress, provoke inflammatory signalling and impair lipid droplet formation, driving progression from steatosis to steatohepatitis. Understanding transport systems, enzyme regulation and cross-talk between phospholipid metabolism and nuclear receptors underpins novel strategies to restore lipid homeostasis and mitigate liver injury in metabolic dysfunction-associated liver disease.

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Phosphatidylcholine Metabolism in Hepatic Disorders publication trend

The graph below shows the total number of articles in phosphatidylcholine metabolism in hepatic disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Phosphatidylcholine (PC): A key glycerophospholipid comprising the outer leaflet of cellular membranes and essential for lipoprotein assembly and lipid transport.

Lysophosphatidylcholine (LPC): A single-fatty-acid phospholipid derived from phosphatidylcholine deacylation, which serves as a substrate for hepatic uptake and lipid droplet formation.

Mfsd2a: A sodium-dependent transporter mediating the uptake of LPC species into hepatocytes to replenish phospholipid pools.

PNPLA7/PNPLA8 axis: A sequential phospholipase pathway that degrades PC into glycerophosphocholine, releasing choline for methyl group metabolism in the liver.

S-adenosylmethionine (SAM): The primary methyl donor generated from methionine, required for phosphatidylethanolamine methylation and other methylation reactions.

Lipid droplet biogenesis: The process by which neutral lipids are encapsulated within a phospholipid monolayer in the endoplasmic reticulum, forming storage organelles.

Nonalcoholic steatohepatitis (NASH): An inflammatory subtype of fatty liver disease characterised by hepatocellular injury, steatosis and fibrosis progression.

VLDL secretion: The assembly and export of very low-density lipoproteins from hepatocytes, a process dependent on adequate PC synthesis.

References

1. Blood-derived lysophospholipid sustains hepatic phospholipids and fat storage necessary for hepatoprotection in overnutrition. Journal of Clinical Investigation (2023).
2. Hepatic phosphatidylcholine catabolism driven by PNPLA7 and PNPLA8 supplies endogenous choline to replenish the methionine cycle with methyl groups. Cell Reports (2023).
3. Oral Supplementation of Phosphatidylcholine Attenuates the Onset of a Diet-Induced Metabolic Dysfunction–Associated Steatohepatitis in Female C57BL/6J Mice. Cellular and Molecular Gastroenterology and Hepatology (2024).
4. The active synthesis of phosphatidylcholine is required for very low density lipoprotein secretion from rat hepatocytes.. Journal of Biological Chemistry (1988).
5. Molecular Distinction of Phosphatidylcholine Synthesis between the CDP-Choline Pathway and Phosphatidylethanolamine Methylation Pathway*. Journal of Biological Chemistry (1999).