ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2016
Liver-specific loss of Perilipin 2 alleviates diet-induced hepatic steatosis, inflammation, and fibrosis.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 153 citations in OpenAlex.
- METTL3 Promotes Lipid Deposition and Pulmonary Fibrosis by Destabilizing PLIN2 in a m6A-Dependent Manner.Journal of cellular and molecular medicine · 2026Article
- Perilipin 2 drives cisplatin-induced acute kidney injury in young but not aged kidneys.American journal of physiology. Renal physiology · 2026Article
- Estradiol mitigates lipid accumulation, oxidative stress, apoptosis, and MAPKs activation in NASH rat model with bilateral orchidectomy.PNAS nexus · 2026Article
- Hepatic inflammation after exposure to a mixture of low-dose arsenic and cadmium in a murine model of fatty liver disease.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Proteomics and Metabolomics Reveal Novel Impacts of Choline Supply on Calf Hepatocytes Experiencing Accumulation During a Fatty Acid Challenge.Metabolites · 2026Article
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- Obesity supersizes macrophage and neutrophil activation after stroke while lipid droplets play a protective role.Journal of neuroinflammation · 2026Article
- Orphan drug uttroside B impedes MASH progression and HCC development in experimental models.JHEP reports : innovation in hepatology · 2026Article
- Interorganelle competition for linoleic acid underlies steatotic liver pathology.bioRxiv : the preprint server for biology · 2026Article
- Emerging roles and therapeutic implications of lipid droplet protein perilipin 2 in liver disease.Genes & diseases · 2026Review
- JMJD8 facilitates hepatic lipid deposition and metabolic dysfunction.American journal of physiology. Endocrinology and metabolism · 2025Article
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- Gut microbiota composition combined with reduced intestinal fatty acid uptake prevents hepatic steatosis in obesity-resistant mice fed a high-fat diet.Scientific reports · 2025Article
- Regulation of Monocyte Perilipin-2 Expression in Acute and Chronic Coronary Syndromes: Pathogenetic Implications.International journal of molecular sciences · 2025Article
- Circadian clocks and periodic anticipated fasting prevent fasting-associated hepatic steatosis in calorie restriction.Cell reports · 2025Article
- Plin2 Coordinates Immune and Metabolic Reprogramming in Lacrimal Gland Aging.Investigative ophthalmology & visual science · 2025Article
- Hepatocyte-specific CLSTN3B ablation impairs lipid droplet maturation and alleviates diet-induced steatohepatitis in mice.bioRxiv : the preprint server for biology · 2025Article
- The AKAP12-PKA axis regulates lipid homeostasis during alcohol-associated liver disease.Signal transduction and targeted therapy · 2025Article
29 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatic inflammation and fibrosis are key elements in the pathogenesis of nonalcoholic steatohepatitis (NASH), a progressive liver disease initiated by excess hepatic lipid accumulation. Lipid droplet protein Perilipin 2 (Plin2) alleviates dietary-induced hepatic steatosis when globally ablated; however, its role in the progression of NASH remains unknown. To investigate this further, we challenged Plin2 liver-specific knockout mice (designated L-KO) and their respective wild-type (WT) controls with a methionine-choline-deficient (MCD) diet for 15 days to induce a NASH phenotype of increased hepatic triglyceride levels through impaired phosphatidylcholine (PC) synthesis and very-low-density lipoprotein (VLDL) secretion. Results on liver weights, body weights, fat tissue mass, and histology in WT and L-KO mice fed the MCD diet revealed signs of hepatic steatosis, fibrosis, and inflammation; however, these effects were blunted in L-KO mice. In addition, levels of PC and VLDL were unchanged, and hepatic steatosis was reduced in L-KO mice fed the MCD diet, due in part to an increase in remodeling of PE to PC via the enzyme phosphatidylethanolamine N-methyltransferase (PEMT). These mice also exhibited decreased hepatic expression of proinflammatory markers cyclooxygenase 2, IL-6, TNF-α, IL-1β, and reduced expression of endoplasmic reticulum (ER) stress proteins C/EBP homologous protein and cleaved caspase-1. Taken together, these results suggest that Plin2 liver-specific ablation alleviates diet-induced hepatic steatosis and inflammation via a PEMT-mediated mechanism that involves compensatory changes in proteins involved in phospholipid remodeling, inflammation, and ER stress that work to alleviate diet-induced NASH. Overall, these findings support a role for Plin2 as a target for NASH therapy.
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