ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2016
Glial cell line-derived neurotrophic factor protects against high-fat diet-induced hepatic steatosis by suppressing hepatic PPAR-γ expression.
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 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Hepatic neurons and metabolically induced liver dysfunction.Nature reviews. Endocrinology · 2026Review
- Therapeutic Nanomaterials in NAFLD: Current Advances and Potential Applications in Patients with Concurrent HBV Infection.International journal of nanomedicine · 2025Review
- A Review of Defatting Strategies for Non-Alcoholic Fatty Liver Disease.International journal of molecular sciences · 2022Review
- Glial cell derived neurotrophic factor prevents western diet and palmitate-induced hepatocyte oxidative damage and death through SIRT3.Scientific reports · 2022Article
- Hydrolyzed Bound Phenolics from Rice Bran Alleviate Hyperlipidemia and Improve Gut Microbiota Dysbiosis in High-Fat-Diet Fed Mice.Nutrients · 2022Article
- Protective Effect of Isoorientin on Oleic Acid-Induced Oxidative Damage and Steatosis in Rat Liver Cells.Frontiers in pharmacology · 2022Article
- Defatting strategies in the current era of liver steatosis.JHEP reports : innovation in hepatology · 2021Review
- Hepatic Autonomic Nervous System and Neurotrophic Factors Regulate the Pathogenesis and Progression of Non-alcoholic Fatty Liver Disease.Frontiers in medicine · 2020Review
- Glial Cell Line-Derived Neurotrophic Factor Enhances Autophagic Flux in Mouse and Rat Hepatocytes and Protects Against Palmitate Lipotoxicity.Hepatology (Baltimore, Md.) · 2019Article
- Simultaneous Detection of Both GDNF and GFRα1 Expression Patterns in the Mouse Central Nervous System.Frontiers in neuroanatomy · 2016Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Glial cell line-derived neurotrophic factor (GDNF) protects against high-fat diet (HFD)-induced hepatic steatosis in mice, however, the mechanisms involved are not known. In this study we investigated the effects of GDNF overexpression and nanoparticle delivery of GDNF in mice on hepatic steatosis and fibrosis and the expression of genes involved in the regulation of hepatic lipid uptake and de novo lipogenesis. Transgenic overexpression of GDNF in liver and other metabolically active tissues was protective against HFD-induced hepatic steatosis. Mice overexpressing GDNF had significantly reduced P62/sequestosome 1 protein levels suggestive of accelerated autophagic clearance. They also had significantly reduced peroxisome proliferator-activated receptor-γ (PPAR-γ) and CD36 gene expression and protein levels, and lower expression of mRNA coding for enzymes involved in de novo lipogenesis. GDNF-loaded nanoparticles were protective against short-term HFD-induced hepatic steatosis and attenuated liver fibrosis in mice with long-standing HFD-induced hepatic steatosis. They also suppressed the liver expression of steatosis-associated genes. In vitro, GDNF suppressed triglyceride accumulation in Hep G2 cells through enhanced p38 mitogen-activated protein kinase-dependent signaling and inhibition of PPAR-γ gene promoter activity. These results show that GDNF acts directly in the liver to protect against HFD-induced cellular stress and that GDNF may have a role in the treatment of nonalcoholic fatty liver disease.
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