ArticleThe Journal of clinical investigation2023
Blood-derived lysophospholipid sustains hepatic phospholipids and fat storage necessary for hepatoprotection in overnutrition.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- MFSD2A in health and disease: lysolipid transport, barrier physiology, and translational boundaries.Molecular biomedicine · 2026Review
- The regulatory network of Mfsd2a in cerebral ischemia: a novel time-targeted intervention framework.Molecular biology reports · 2026Review
- Article
- LPLAT7 reutilizes unsaturated 1-lysophospholipids formed during lysosomal phospholipid degradation.Journal of lipid research · 2026Article
- Plasma lipidome mediates the causal effect of chronic hepatitis B on cirrhosis: A Mendelian randomization study.Medicine · 2026Article
- Article
- Mfsd2a is important for maintaining epidermal homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Choline Deficiency Drives the Inflammation-Fibrosis Cascade: A Spatiotemporal Atlas of Hepatic Injury from Weeks 6 to 10.Antioxidants (Basel, Switzerland) · 2026Article
- Hepatic Metabolic Dysregulation as a Potential Amplifier of Leukemogenesis Following mRNA Vaccination: A Novel Mechanistic Hypothesis.Medicina (Kaunas, Lithuania) · 2025Article
- Rutin Attenuates Oxidative Stress Responses and Hepatocyte Metabolomics in β-Hydroxybutyric Acid-Induced Hepatocyte Injury in Calves.International journal of molecular sciences · 2025Article
- Label-Free Electrochemical Cell-Based Biosensor for Toxicity Assay of Water-Soluble Form of Phosphatidylcholine.Biomedicines · 2025Article
- The effect of Hepato Forte in reducing hypercholesterolemia and DNA fragmentation induced by high cholesterol in male albino rats.Open veterinary journal · 2025Article
- Hepatic Steatosis and Fibrosis, Cardiorespiratory Fitness, and Metabolic Mediators in the Community.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD.Clinical and molecular hepatology · 2024Article
- Review
- Lipidome Changes Associated with a Diet-Induced Reduction in Hepatic Fat among Adolescent Boys with Metabolic Dysfunction-Associated Steatotic Liver Disease.Metabolites · 2024Article
- Exposure to PFAS chemicals induces sex-dependent alterations in key rate-limiting steps of lipid metabolism in liver steatosis.Frontiers in toxicology · 2024Article
- Integration of Transcriptomics and Lipidomics Profiling to Reveal the Therapeutic Mechanism UnderlyingNutrients · 2023Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The liver has a high demand for phosphatidylcholine (PC), particularly in overnutrition, where reduced phospholipid levels have been implicated in the development of nonalcoholic fatty liver disease (NAFLD). Whether other pathways exist in addition to de novo PC synthesis that contribute to hepatic PC pools remains unknown. Here, we identified the lysophosphatidylcholine (LPC) transporter major facilitator superfamily domain containing 2A (Mfsd2a) as critical for maintaining hepatic phospholipid pools. Hepatic Mfsd2a expression was induced in patients having NAFLD and in mice in response to dietary fat via glucocorticoid receptor action. Mfsd2a liver-specific deficiency in mice (L2aKO) led to a robust nonalcoholic steatohepatitis-like (NASH-like) phenotype within just 2 weeks of dietary fat challenge associated with reduced hepatic phospholipids containing linoleic acid. Reducing dietary choline intake in L2aKO mice exacerbated liver pathology and deficiency of liver phospholipids containing polyunsaturated fatty acids (PUFAs). Treating hepatocytes with LPCs containing oleate and linoleate, two abundant blood-derived LPCs, specifically induced lipid droplet biogenesis and contributed to phospholipid pools, while LPC containing the omega-3 fatty acid docosahexaenoic acid (DHA) promoted lipid droplet formation and suppressed lipogenesis. This study revealed that PUFA-containing LPCs drive hepatic lipid droplet formation, suppress lipogenesis, and sustain hepatic phospholipid pools - processes that are critical for protecting the liver from excess dietary fat.
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