PNPLA3 expression and its impact on the liver: current perspectives
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), known as I148M variant, is one of the best characterized and deeply investigated variants in several clinical scenarios, because of its tight correlation with increased risk for developing hepatic steatosis and more aggressive part of the disease spectrum, such as nonalcoholic steatohepatitis, advanced fibrosis and cirrhosis. Further, the I148M variant is positively associated with alcoholic liver diseases, chronic hepatitis C-related cirrhosis and hepatocellular carcinoma. The native gene encodes for a protein that has not yet a fully defined role in liver lipid metabolism and, according to recent observations, seems to be divergently regulated among distinct liver cells type, such as hepatic stellate cells. Therefore, the aim of this review is to collect the latest data regarding PNPLA3 expression in human liver and to analyze the impact of its genetic variant in human hepatic pathologies. Moreover, a description of the current biochemical and metabolic data pertaining to PNPLA3 function in both animal models and in vitro studies is summarized to allow a better understanding of the relevant pathophysiological role of this enzyme in the progression of hepatic diseases.
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PNPLA3 expression differs between humans and mice: in mice it is predominantly in adipose tissue with 50-100 times higher expression than liver; in humans it is highest in liver, and in human liver stellate cells express more than twice as much as hepatocytes.
“In mice, Pnpla3 is predominantly expressed in adipose tissue, where its expression level is 50–100 times higher than in the liver [50,51,52].”
From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [52]
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Self-citation
- Authors
- Bruschi, F. V., Tardelli, M., Claudel, T., & Trauner, M.
- Affiliations
- Medical University of Vienna (AT)
- Corresponding author
- Trauner, Michael
- Venue
- Hepatic Medicine: Evidence and Research
- Publisher
- Informa UK Limited
- Published
- 2017-11
- Volume
- Volume 9
- Pages
- 55-66
- ISSN
- 1179-1535 (ISSN-L)
- PMC
- PMC5683790
- OpenAlex
- W2767887007
- Cited by
- 81
- References
- 97
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 5 · 2023: 5 · 2022: 13 · 2021: 12 · 2020: 19 · 2019: 11 · 2018: 4
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Hepatic Medicine Evidence and Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- PNPLA3, I148M variant, hepatic lipid metabolism, hepatic steatosis, nonalcoholic steatohepatitis, liver fibrosis, liver cirrhosis, alcoholic liver disease, chronic hepatitis C, hepatocellular carcinoma, hepatic stellate cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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