ArticleBiochimica et biophysica acta2016
Purinergic receptor X7 mediates leptin induced GLUT4 function in stellate cells in nonalcoholic steatohepatitis.
Article in Biochimica et biophysica acta, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Liver Fibrosis and Purinergic Signaling: Autocrine-Paracrine Role of ATP in Liver Damage.International journal of molecular sciences · 2026Review
- The P2X4-P2X7 purinergic axis in alcohol-related liver disease: from fibrogenesis to immunotherapy resistance.Purinergic signalling · 2026Review
- Biliary atresia-related liver fibrosis.Frontiers in cell and developmental biology · 2026Review
- Macrophage inhibition in the alleviation of nonalcoholic steatohepatitis caused by bariatric surgery.Genes and immunity · 2025Article
- Metabolic Sparks in the Liver: Metabolic and Epigenetic Reprogramming in Hepatic Stellate Cells Activation and Its Implications for Human Metabolic Diseases.Diabetes & metabolism journal · 2025Review
- Screening the human druggable genome identifies ABHD17B as an anti-fibrotic target in hepatic stellate cells.Nature communications · 2025Article
- Unraveling the Emerging Niche Role of Hepatic Stellate Cell-derived Exosomes in Liver Diseases.Journal of clinical and translational hepatology · 2023Review
- Review
- Metabolic Reprogramming of Liver Fibrosis.Cells · 2021Review
- The Purinergic P2X7 Receptor-NLRP3 Inflammasome Pathway: A New Target in Alcoholic Liver Disease?International journal of molecular sciences · 2021Review
- The Power of Plasticity-Metabolic Regulation of Hepatic Stellate Cells.Cell metabolism · 2021Review
- Purinergic signalling in liver diseases: Pathological functions and therapeutic opportunities.JHEP reports : innovation in hepatology · 2020Review
- Role of cytoglobin, a novel radical scavenger, in stellate cell activation and hepatic fibrosis.Clinical and molecular hepatology · 2020Review
- Review
- Pathophysiology of NAFLD and NASH in Experimental Models: The Role of Food Intake Regulating Peptides.Frontiers in endocrinology · 2020Review
- Review
- A Mitochondrial VDAC1-Based Peptide Greatly Suppresses Steatosis and NASH-Associated Pathologies in a Mouse Model.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Increased butyrate priming in the gut stalls microbiome associated-gastrointestinal inflammation and hepatic metabolic reprogramming in a mouse model of Gulf War Illness.Toxicology and applied pharmacology · 2018Article
- The potential of P2X7 receptors as a therapeutic target, including inflammation and tumour progression.Purinergic signalling · 2018Review
- Purinergic Signalling: Therapeutic Developments.Frontiers in pharmacology · 2017Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Metabolic oxidative stress via CYP2E1 can act as a second hit in NASH progression. Our previous studies have shown that oxidative stress in NASH causes higher leptin levels and induces purinergic receptor X7 (P2X7r). We tested the hypothesis that higher circulating leptin due to CYP2E1-mediated oxidative stress induces P2X7r. P2X7r in turn activates stellate cells and causes increased proliferation via modulating Glut4, the glucose transporter, and increased intracellular glucose. Using a high fat diet-fed NAFLD model where bromodichloromethane (BDCM) was administered to induce CYP2E1-mediated oxidative stress, we show that P2X7r expression and protein levels were leptin and CYP2E1 dependent. P2X7r KO mice had significantly decreased stellate cell proliferation. Human NASH livers showed marked increase in P2X7r, and Glut4 in α-SMA positive cells. NASH livers had significant increase in Glut4 protein and phosphorylated AKT, needed for Glut4 translocation while leptin KO and P2X7r KO mice showed marked decrease in Glut4 levels primarily in stellate cells. Mechanistically stellate cells showed increase in phosphorylated AKT, Glut4 protein and localization in the membrane following administration of P2X7r agonist or leptin+P2X7r agonist, while use of P2X7r antagonist or AKT inhibitor attenuated the response suggesting that leptin-P2X7r axis in concert but not leptin alone is responsible for the Glut4 induction and translocation. Finally P2X7r-agonist and leptin caused an increase in intracellular glucose and consumption by increasing the activity of hexokinase. In conclusion, the study shows a novel role of leptin-induced P2X7r in modulating Glut4 induction and translocation in hepatic stellate cells, that are key to NASH progression.
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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.