ArticleJournal of hepatology2011
Distinct regulation of adiponutrin/PNPLA3 gene expression by the transcription factors ChREBP and SREBP1c in mouse and human hepatocytes.
Article in Journal of hepatology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 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
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 131 citations in OpenAlex.
- Pooled it
- The role of hepatocyte epigenetics in the pathogenesis of metabolic dysfunction-associated steatotic liver disease.Communications medicine · 2026Review
- Genomic Signatures of MASLD: How Genomics Is Redefining Our Understanding of Metabolic Liver Disease.International journal of molecular sciences · 2025Review
- PNPLA3 I148M variant links to adverse metabolic traits in MASLD during fasting and feeding.JHEP reports : innovation in hepatology · 2025Article
- Article
- Experimental Models to Investigate PNPLA3 in Liver Steatosis.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Genetic predisposition of metabolic dysfunction-associated steatotic liver disease: a population-based genome-wide association study.Hepatology international · 2025Article
- GlobalNature metabolism · 2024Article
- Non-alcoholic fatty liver disease: Role of PNPLA3 and its association with environmental chemicals.Archives of clinical toxicology · 2024Article
- The role of ChREBP in carbohydrate sensing and NAFLD development.Nature reviews. Endocrinology · 2023Review
- Unmasking the enigma of lipid metabolism in metabolic dysfunction-associated steatotic liver disease: from mechanism to the clinic.Frontiers in medicine · 2023Review
- Genetic Polymorphisms and Diversity in Nonalcoholic Fatty Liver Disease (NAFLD): A Mini Review.Biomedicines · 2022Review
- Human hepatocyte PNPLA3-148M exacerbates rapid non-alcoholic fatty liver disease development in chimeric mice.Cell reports · 2022Article
- KHK, PNPLA3 and PPAR as Novel Targets for the Anti-Steatotic Action of Bempedoic Acid.Biomedicines · 2022Article
- SIRT1 mediates nutritional regulation of SREBP-1c-driven hepatic PNPLA3 transcription via modulation of H3k9 acetylation.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2022Article
- ChREBP-driven DNL and PNPLA3 Expression Induced by Liquid Fructose are Essential in the Production of Fatty Liver and Hypertriglyceridemia in a High-Fat Diet-Fed Rat Model.Molecular nutrition & food research · 2022Article
- TTC39B destabilizes retinoblastoma protein promoting hepatic lipogenesis in a sex-specific fashion.Journal of hepatology · 2022Article
- Review
- Genetic susceptibility to hepatocellular carcinoma in chromosome 22q13.31, findings of a genome-wide association study.JGH open : an open access journal of gastroenterology and hepatology · 2021Article
- Lipolysis: cellular mechanisms for lipid mobilization from fat stores.Nature metabolism · 2021Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on byFocus.2011
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsThe adiponutrin/PNPLA3 (patatin-like phospholipase domain-containing protein 3) variant I148M has recently emerged as an important marker of human fatty liver disease. In order to understand the role of the adiponutrin/PNPLA3 protein, we investigated the regulation of its expression in both human and mouse hepatocytes.
methodsAdiponutrin/PNPLA3 and lipogenic enzyme expression was determined by real-time PCR analysis in a wide panel of analysis in vivo in the mouse liver and in vitro in murine hepatocytes and human hepatocyte cell lines infected with ChREBP or SREBP1c-expressing adenoviruses.
resultsWe show that in the mouse liver, adiponutrin/PNPLA3 gene expression is under the direct transcriptional control of ChREBP (carbohydrate-response element-binding protein) and SREBP1c (sterol regulatory element binding protein1c) in response to glucose and insulin, respectively. In silico analysis revealed the presence of a ChoRE (carbohydrate response element) and of a SRE (sterol response element) binding site on the mouse adiponutrin/PNPLA3 gene promoter. Point mutation analysis in reporter gene assays identified the functional response of these two binding sites in the mouse adiponutrin/PNPLA3 promoter. In contrast, in human immortalized hepatocytes and in HepG2 hepatoma cells, only SREBP1c was able to induce adiponutrin/PNPLA3 expression, whereas ChREBP was unable to modulate its expression.
conclusionsAll together, our results suggest that adiponutrin/PNPLA3 is regulated by two key factors of the glycolytic and lipogenic pathways, raising the question of its implication in the metabolism of carbohydrates and lipids.
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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.