ArticleNature communications2024
PNPLA3 is a triglyceride lipase that mobilizes polyunsaturated fatty acids to facilitate hepatic secretion of large-sized very low-density lipoprotein.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 2 of them syntheses that pooled it.
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
66 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Impact of PNPLA3 I148M on Drug-Induced Hepatocellular Liver Injury: A Systematic Review and Meta-Analysis.Liver international : official journal of the International Association for the Study of the Liver · 2025Pooled it
- Meta-Analysis: Effects of Steatotic Liver Disease-Associated Genetic Risk Alleles on Longitudinal Outcomes.Alimentary pharmacology & therapeutics · 2025Pooled it
- Genetics of MASLD: a diabetes perspective.Diabetologia · 2026Review
- Metabolic dysfunction-associated steatotic liver disease: pathogenic mechanisms and exercise-induced molecular adaptations.Lipids in health and disease · 2026Review
- The Human PNPLA3FASEB bioAdvances · 2026Article
- The Phospholipase AJournal of lipid and atherosclerosis · 2026Review
- Autophagy in MASLD: A Metabolic and Precision Medicine Perspective.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Molecular mechanisms and pathogenesis of MASH.Nature · 2026Review
- Genetic and genomic insights across the steatotic liver disease spectrum.Clinical and molecular hepatology · 2026Review
- The Implications of Lipoprotein(a) in MASLD.Current cardiology reports · 2026Review
- Review
- ANGPTL4 Exacerbates Renal Injury in Diabetic Kidney Disease by Impairing Podocyte Lipophagy via Compromised Lysosomal Degradative Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Genome-wide association and polygenic risk score analyses of MASLD-related hepatic steatosis severity in a Taiwanese Han population.Cell & bioscience · 2026Article
- Tissue-specific regulation of PNPLA3 promotes lipid remodeling in response to dietary and environmental challenges.Journal of hepatology · 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
- Hepatic Lipoprotein Production, Cardiometabolic Phenotypes, and Subtypes of Steatotic Liver Disease.Circulation research · 2026Review
- Integrating CRISPR genome editing with liver organoid and hiPSC-derived microfluidic platforms to model metabolic dysfunction-associated steatotic liver disease.Biochemistry and biophysics reports · 2026Review
- Comparative Hepatic Transcriptomic Analysis Reveals Metabolic Regulatory Differences Between Qilian and Oula Sheep.Veterinary sciences · 2026Article
- PNPLA3-I148M reduces hepatic triacylglycerol secretion and mitigates diet induced left ventricular diastolic dysfunction.Scientific reports · 2026Article
- Appropriate Dietary Levels of Soybean Lecithin and Krill Oil Phospholipids Promote Growth, Antioxidant Capacity, and Lipid Metabolism While Reducing Lipid Deposition in Atlantic Salmon (Animals : an open access journal from MDPI · 2026Article
6 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
10 authors.
Funding
Abstract
The I148M variant of PNPLA3 is closely associated with hepatic steatosis. Recent evidence indicates that the I148M mutant functions as an inhibitor of PNPLA2/ATGL-mediated lipolysis, leaving the role of wild-type PNPLA3 undefined. Despite showing a triglyceride hydrolase activity in vitro, PNPLA3 has yet to be established as a lipase in vivo. Here, we show that PNPLA3 preferentially hydrolyzes polyunsaturated triglycerides, mobilizing polyunsaturated fatty acids for phospholipid desaturation and enhancing hepatic secretion of triglyceride-rich lipoproteins. Under lipogenic conditions, mice with liver-specific knockout or acute knockdown of PNPLA3 exhibit aggravated liver steatosis and reduced plasma VLDL-triglyceride levels. Similarly, I148M-knockin mice show decreased hepatic triglyceride secretion during lipogenic stimulation. Our results highlight a specific context whereby the wild-type PNPLA3 facilitates the balance between hepatic triglyceride storage and secretion, and suggest the potential contribution of a loss-of-function by the I148M variant to the development of fatty liver disease in humans.
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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.