ArticleThe Journal of clinical investigation2012
Chronic overexpression of PNPLA3I148M in mouse liver causes hepatic steatosis.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers.
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Who cites it
163 citing papers in PubMed, 272 citations in OpenAlex.
- Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB genes are associated with development and progression of nonalcoholic fatty liver disease in Japan.Human genetics · 2013Trial
- Molecular mechanisms and pathogenesis of MASH.Nature · 2026Review
- Physiologically relevant media are associated with overlapping metabolic responses in primary human hepatocytes and Huh7 cells.Physiological reports · 2026Article
- Hepatic Lipoprotein Production, Cardiometabolic Phenotypes, and Subtypes of Steatotic Liver Disease.Circulation research · 2026Review
- PNPLA3-I148M reduces hepatic triacylglycerol secretion and mitigates diet induced left ventricular diastolic dysfunction.Scientific reports · 2026Article
- MAFLD: a ferroptotic disease.Trends in molecular medicine · 2026Review
- PNPLA3-I148M genetic variant rewires lipid metabolism to drive programmed cell death in human hepatocytes.JCI insight · 2025Article
- Metabolic dysfunction‑associated steatotic liver disease: Pathogenesis, model and treatment (Review).International journal of molecular medicine · 2025Review
- Cross-ancestry discovery of genetic risk variants for lean metabolic dysfunction-associated steatotic liver disease.Cell & bioscience · 2025Article
- Sphingosine kinase 2 deficiency impairs VLDL secretion by inhibiting mTORC2 phosphorylation and activating chaperone-mediated autophagy.Cell death and differentiation · 2025Article
- PNPLA3 I148M variant is the main driver of weight gain after hepatitis C cure.Scientific reports · 2025Article
- Gene-based therapies for steatotic liver disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Article
- PNPLA3(148M) is a gain-of-function mutation that promotes hepatic steatosis by inhibiting ATGL-mediated triglyceride hydrolysis.Journal of hepatology · 2025Article
- Experimental Models to Investigate PNPLA3 in Liver Steatosis.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Fishing for Solutions: How Pre-Conceptional Fish Oil Supplementation in Obese Fathers Reduces Risk of Non-Alcoholic Fatty Liver Disease in Offspring Mice.Molecular nutrition & food research · 2025Article
- Unraveling Metabolic Dysfunction-Associated Steatotic Liver Disease Through the Use of Omics Technologies.International journal of molecular sciences · 2025Review
- At the Crossroads of Health and Disease: Consequences of Fat in the Liver.Annual review of physiology · 2025Review
- Halting Hypercaloric Feeding in Liver Chimeric Mice Rapidly Resolves Human Hepatocyte Steatosis.Gastro hep advances · 2025Article
- Statin-associated regulation of hepatic PNPLA3 in patients without known liver disease.Journal of internal medicine · 2025Article
103 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
A genetic variant in PNPLA3 (PNPLA3(I148M)), a triacylglycerol (TAG) hydrolase, is a major risk factor for nonalcoholic fatty liver disease (NAFLD); however, the mechanism underlying this association is not known. To develop an animal model of PNPLA3-induced fatty liver disease, we generated transgenic mice that overexpress similar amounts of wild-type PNPLA3 (PNPLA3(WT)) or mutant PNPLA3 (PNPLA3(I148M)) either in liver or adipose tissue. Overexpression of the transgenes in adipose tissue did not affect liver fat content. Expression of PNPLA3(I148M), but not PNPLA3(WT), in liver recapitulated the fatty liver phenotype as well as other metabolic features associated with this allele in humans. Metabolic studies provided evidence for 3 distinct alterations in hepatic TAG metabolism in PNPLA3(I148M) transgenic mice: increased formation of fatty acids and TAG, impaired hydrolysis of TAG, and relative depletion of TAG long-chain polyunsaturated fatty acids. These findings suggest that PNPLA3 plays a role in remodeling TAG in lipid droplets, as they accumulate in response to food intake, and that the increase in hepatic TAG levels associated with the I148M substitution results from multiple changes in hepatic TAG metabolism. The development of an animal model that recapitulates the metabolic phenotype of the allele in humans provides a new platform in which to elucidate the role of PNLPA3(I148M) in NAFLD.
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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.