ArticleLiver international : official journal of the International Association for the Study of the Liver2020
Metabolic regulation of hepatic PNPLA3 expression and severity of liver fibrosis in patients with NASH.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Longevity-driven hepatic transcriptional programs mediate resilience to diet-induced liver injury in Ames dwarf mice.GeroScience · 2026Article
- A PNPLA3-NACC1-RIPK3 pathway mediates macrophage necroptosis and inflammation in MASLD.Hepatology communications · 2026Article
- Reduced Esterification Rather Than Increased Hydrolysis Is Causative for Loss of Hepatic Retinoids Upon CClLiver international : official journal of the International Association for the Study of the Liver · 2025Article
- Role of PNPLA3 in Hepatic Stellate Cells and Hepatic Cellular Crosstalk.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Heterocyclic Amines Disrupt Lipid Homeostasis in Cryopreserved Human Hepatocytes.Cardiovascular toxicology · 2024Article
- Exploring the role of genetic variations in NAFLD: implications for disease pathogenesis and precision medicine approaches.European journal of medical research · 2024Review
- Mechanisms of liver fibrosis in metabolic syndrome.eGastroenterology · 2023Article
- Role of the Hippo pathway in liver regeneration and repair: recent advances.Inflammation and regeneration · 2022Review
- Update on Non-Alcoholic Fatty Liver Disease-Associated Single Nucleotide Polymorphisms and Their Involvement in Liver Steatosis, Inflammation, and Fibrosis: A Narrative ReviewIranian biomedical journal · 2022Review
- Perturbation of Wnt/β-catenin signaling and sexual dimorphism in non-alcoholic fatty liver disease.Hepatology research : the official journal of the Japan Society of Hepatology · 2022Article
- Responsiveness of PNPLA3 and lipid-related transcription factors is dependent upon fatty acid profile in primary bovine hepatocytes.Scientific reports · 2022Article
- Promising diagnostic biomarkers of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: From clinical proteomics to microbiome.World journal of hepatology · 2021Review
- Priming, Triggering, Adaptation and Senescence (PTAS): A Hypothesis for a Common Damage Mechanism of Steatohepatitis.International journal of molecular sciences · 2021Article
- Genetics, Immunity and Nutrition Boost the Switching from NASH to HCC.Biomedicines · 2021Review
- Genetics Is of the Essence to Face NAFLD.Biomedicines · 2021Review
- Combined effects of PNPLA3, TM6SF2 and HSD17B13 variants on severity of biopsy-proven non-alcoholic fatty liver disease.Hepatology international · 2021Article
- PNPLA3 downregulation exacerbates the fibrotic response in human hepatic stellate cells.PloS one · 2021Article
- PNPLA3 I148M Up-Regulates Hedgehog and Yap Signaling in Human Hepatic Stellate Cells.International journal of molecular sciences · 2020Article
- The Role of Metabolic Lipases in the Pathogenesis and Management of Liver Disease.Hepatology (Baltimore, Md.) · 2020Review
- Metabolic regulation of hepatic PNPLA3 expression and severity of liver fibrosis in patients with NASH.Liver international : official journal of the International Association for the Study of the Liver · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsThe genetic PNPLA3 polymorphism I148M has been extensively associated with higher risk for development and progression of NAFLD towards NASH.
methodsPNPLA3 and α-SMA expression were quantified in liver biopsies collected from NASH patients (n = 26) with different fibrosis stages and PNPLA3 genotypes. To study the potential mechanisms driving PNPLA3 expression during NASH progression towards fibrosis, hepatocytes and hepatic stellate cells (HSCs) were cultivated in low and high glucose medium. Moreover, hepatocytes were treated with increasing concentrations of palmitic acid alone or in combination with glucose. Conditioned media were collected from challenged hepatocytes to stimulate HSCs.
resultsTissue expression of PNPLA3 was significantly enhanced in biopsies of patients carrying the I148M polymorphism compared to wild type (WT). In NASH biopsies, PNPLA3 significantly correlated with fibrosis stage and α-SMA levels independently of PNPLA3 genotype. In line, PNPLA3 expression was higher in α-SMA positive cells. Low glucose increased PNPLA3 in HSCs, whereas high glucose induced PNPLA3 and de-novo lipogenesis-related genes expression in hepatocytes. Palmitic acid induced fat accumulation and cell stress markers in hepatocytes, which could be counteracted by oleic acid. Conditioned media collected from lipotoxic challenged hepatocytes markedly induced PNPLA3 mRNA and protein levels, fibrogenic and autophagic markers and promoted migration in HSCs. Notably, conditioned media collected from hepatocytes cultivated with both glucose and palmitic acid exacerbated HSCs migration, PNPLA3 and fibrogenic gene expression, promoting release of cytokines from HSCs.
conclusionsCollectively, our observations uncover the diverse metabolic regulation of PNPLA3 among different hepatic cell populations and support its relation to fibrosis progression.
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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.