ArticleHepatology (Baltimore, Md.)2015
Pnpla3I148M knockin mice accumulate PNPLA3 on lipid droplets and develop hepatic steatosis.
Article in Hepatology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 202 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
202 citing papers in PubMed, 1 synthesis or guideline pooled it, 362 citations in OpenAlex.
- Genetic factors that affect nonalcoholic fatty liver disease: A systematic clinical review.World journal of gastroenterology · 2016Pooled it
- Increased Genetic Risk for β-Cell Failure Is Associated With β-Cell Function Decline in People With Prediabetes.Diabetes · 2024Trial
- Biomarkers of NAFLD progression: a lipidomics approach to an epidemic.Journal of lipid research · 2015Trial
- Molecular mechanisms and pathogenesis of MASH.Nature · 2026Review
- The Human PNPLA3FASEB bioAdvances · 2026Article
- Beyond Fat: Reframing MASLD Through Genetics, Clonal Biology, and Precision Hepatology.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Tissue-specific regulation of PNPLA3 promotes lipid remodeling in response to dietary and environmental challenges.Journal of hepatology · 2026Article
- Hepatic Lipoprotein Production, Cardiometabolic Phenotypes, and Subtypes of Steatotic Liver Disease.Circulation research · 2026Review
- Article
- Membrane bridges and nanodomain partitioning govern membrane protein targeting to lipid droplets.Nature cell biology · 2026Article
- Germline mutations and somatic mosaicism in steatotic liver diseases and related liver carcinogenesis.Nature reviews. Gastroenterology & hepatology · 2026Review
- Mechanisms and therapeutic insights into MASH-associated fibrosis.Trends in endocrinology and metabolism: TEM · 2026Review
- Emerging Insights into the Liver-Pancreas Axis: A Central Hub in the Pathogenesis of Diabetes and Metabolic Diseases.Biomolecules · 2026Review
- Comparison and Characteristics of MASLD Mouse Models.Biomedicines · 2026Review
- Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models.Nature reviews. Gastroenterology & hepatology · 2026Review
- Integrated chromatin and transcriptomic profiling reveals sex-specific mechanisms of gene regulation in hepatic nutrient responses.PLoS biology · 2026Article
- Genome-wide association study identifies three PNPLA3/SAMM50 SNPs associated with HCC development in non-viral liver disease.JHEP reports : innovation in hepatology · 2026Article
- A PNPLA3-NACC1-RIPK3 pathway mediates macrophage necroptosis and inflammation in MASLD.Hepatology communications · 2026Article
- Interorganelle competition for linoleic acid underlies steatotic liver pathology.bioRxiv : the preprint server for biology · 2026Article
- Loss of TMEM55B modulates lipid metabolism through dysregulated lipophagy and mitochondrial function.Cell death & disease · 2026Article
142 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledA sequence polymorphism (rs738409, I148M) in patatin-like phospholipid domain containing protein 3 (PNPLA3) is strongly associated with nonalcoholic fatty liver disease (NAFLD), but the mechanistic basis for this association remains enigmatic. Neither ablation nor overexpression of wild-type PNPLA3 affects liver fat content in mice, whereas hepatic overexpression of the human 148M transgene causes steatosis. To determine whether the 148M allele causes fat accumulation in the liver when expressed at physiological levels, we introduced a methionine codon at position 148 of the mouse Pnpla3 gene. Knockin mice had normal levels of hepatic fat on a chow diet, but when challenged with a high-sucrose diet their liver fat levels increased 2 to 3-fold compared to wild-type littermates without any associated changes in glucose homeostasis. The increased liver fat in the knockin mice was accompanied by a 40-fold increase in PNPLA3 on hepatic lipid droplets, with no increase in hepatic PNPLA3 messenger RNA (mRNA). Similar results were obtained when the catalytic dyad of PNPLA3 was inactivated by substituting the catalytic serine with alanine (S47A).
conclusionThese data provide the first direct evidence that physiological expression of PNPLA3 148M variant causes NAFLD, and that the accumulation of catalytically inactive PNPLA3 on the surfaces of lipid droplets is associated with the accumulation of TG in the liver.
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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.