ArticleJournal of lipid research2019
PNPLA2 influences secretion of triglyceride-rich lipoproteins by human hepatoma cells.
Article in Journal of lipid research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
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- AAV9-mediated gene supplementation therapy prevents and rescues arrhythmogenic cardiomyopathy in Pnpla2-mutated mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Human genetics of metabolic dysfunction-associated steatotic liver disease: from variants to cause to precision treatment.The Journal of clinical investigation · 2025Review
- Analysis of Lipid Metabolism in Adipose Tissue and Liver of Chinese Soft-Shelled TurtleInternational journal of molecular sciences · 2024Article
- Transcriptome Sequencing Reveals Autophagy Networks in Rat Livers during the Development of NAFLD and Identifies Autophagy Hub Genes.International journal of molecular sciences · 2023Article
- Transcriptional Inhibition of AGPAT2 Induces Abnormal Lipid Metabolism and Oxidative Stress in the Liver of Nile TilapiaAntioxidants (Basel, Switzerland) · 2023Article
- Phenome-wide and expression quantitative trait locus associations of coronavirus disease 2019 genetic risk loci.iScience · 2021Article
- Nuclear-Encoded lncRNAMolecular therapy. Nucleic acids · 2021Article
- Downregulation of adipose triglyceride lipase by EB viral-encoded LMP2A links lipid accumulation to increased migration in nasopharyngeal carcinoma.Molecular oncology · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patatin-like phospholipase domain-containing proteins (PNPLAs) are involved in triglyceride hydrolysis and lipid-droplet homeostasis in mice, but the physiological significance of the PNPLAs for triglyceride metabolism in human hepatocytes is unclear. Here, we investigate the roles of PNPLA2, PNPLA3, and PNPLA4 in triglyceride metabolism of human Huh7 and HepG2 hepatoma cells using gene-specific inhibition methods. siRNA inhibition of PNPLA3 or PNPLA4 is not associated with changes in triglyceride hydrolysis, secretion of triglyceride-rich lipoproteins (TRLs), or triglyceride accumulation. However, PNPLA2 siRNA inhibition, both in the absence and presence of oleate-containing medium, or treatment with the PNPLA2 inhibitor Atglistatin reduced intracellular triglyceride hydrolysis and decreased TRL secretion. In contrast, PNPLA2 inhibition showed no effects on lipid-droplet homeostasis, which is the primary physiological function of PNPLA2 in nonhepatic tissues. Moreover, confocal microscopy analysis found no clear evidence for the localization of PNPLA2 around lipid droplets. However, significant colocalization of PNPLA2 with the endoplasmic reticulum marker protein disulfide-isomerase was found in HepG2 and Huh7 cells with Rcoloc values of 0.61 ± 0.06 and 0.81 ± 0.05, respectively. In conclusion, PNPLA2 influences TRL secretion, but is not involved in lipid-droplet homeostasis in human hepatoma cells, a physiological role that is quite distinct from the metabolic function of PNPLA2 in nonhepatic tissues.
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