ArticleJCI insight2019
Human PNPLA3-I148M variant increases hepatic retention of polyunsaturated fatty acids.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
88 citing papers in PubMed, 154 citations in OpenAlex.
- Prime editing enables isogenic modeling of PNPLA3-I148M-associated lipotoxicity in hepatocytes.Molecular therapy. Nucleic acids · 2026Article
- Genetic and genomic insights across the steatotic liver disease spectrum.Clinical and molecular hepatology · 2026Review
- A membrane homeostatic response to lipid overload coordinates fatty acid metabolism.bioRxiv : the preprint server for biology · 2026Article
- Replication of acne susceptibility loci and gene-environment interactions with screen time in Singapore and Malaysia Chinese population.JID innovations : skin science from molecules to population health · 2026Article
- Tissue-specific regulation of PNPLA3 promotes lipid remodeling in response to dietary and environmental challenges.Journal of hepatology · 2026Article
- Reduction in Hepatic Phosphatidylcholine Biosynthesis Promotes MASH Through Copper Deficiency.bioRxiv : the preprint server for biology · 2026Article
- PNPLA3-I148M reduces hepatic triacylglycerol secretion and mitigates diet induced left ventricular diastolic dysfunction.Scientific reports · 2026Article
- Untargeted plasma lipidomic profiling associated with pediatric metabolic dysfunction-associated steatohepatitis (MASH).Lipids in health and disease · 2026Article
- A Global Perspective on Metabolic Dysfunction-Associated Steatotic Liver Disease: From Molecular Mechanisms to Therapeutic Strategy Innovation.Nutrients · 2026Review
- Interactions Between the Gut Microbiome and Genetic and Clinical Risk Factors for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Patients with Type 2 Diabetes Mellitus from Different Geographical Regions of Argentina.Life (Basel, Switzerland) · 2026Article
- Genomic Signatures of MASLD: How Genomics Is Redefining Our Understanding of Metabolic Liver Disease.International journal of molecular sciences · 2025Review
- FSP1-mediated lipid droplet quality control prevents neutral lipid peroxidation and ferroptosis.Nature cell biology · 2025Article
- Human genetics of steatotic liver disease: insights into insulin resistance and lipid metabolism.Nature metabolism · 2025Review
- Mildly elevated liver lipid content is characterised by reduced insulin sensitivity.JHEP reports : innovation in hepatology · 2025Article
- Gene-based therapies for steatotic liver disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- VLDL lipidomics reveals hepatocellular lipidome changes in metabolic dysfunction-associated steatotic liver disease.Hepatology communications · 2025Article
- Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction-associated steatohepatitis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cellular communication networks in fibrosis: Insights from the MASLD pig model.Hepatology communications · 2025Article
- Experimental Models to Investigate PNPLA3 in Liver Steatosis.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Targeting PNPLA3 to Treat MASH and MASH Related Fibrosis and Cirrhosis.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 8 institutions in 4 countries.
Funding
Abstract
The common patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant I148M predisposes to nonalcoholic liver disease but not its metabolic sequelae. We compared the handling of labeled polyunsaturated fatty acids (PUFAs) and saturated fatty acids (SFA) in vivo in humans and in cells harboring different PNPLA3 genotypes. In 148M homozygous individuals, triglycerides (TGs) in very low-density lipoproteins (VLDL) were depleted of PUFAs both under fasting and postprandial conditions compared with 148I homozygotes, and the PUFA/SFA ratio in VLDL-TGs was lower relative to the chylomicron precursor pool. In human PNPLA3-148M and PNPLA3-KO cells, PUFA but not SFA incorporation into TGs was increased at the expense of phosphatidylcholines, and under lipolytic conditions, PUFA-containing diacylglycerols (DAGs) accumulated compared with PNPLA3-148I cells. Polyunsaturated TGs were increased, while phosphatidylcholines (PCs) were decreased in the human liver in 148M homozygous individuals as compared with 148I homozygotes. We conclude that human PNPLA3-I148M is a loss-of-function allele that remodels liver TGs in a polyunsaturated direction by impairing hydrolysis/transacylation of PUFAs from DAGs to feed phosphatidylcholine synthesis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.