ArticleLipids in health and disease2019
Hepatitis C virus nonstructural protein 5A perturbs lipid metabolism by modulating AMPK/SREBP-1c signaling.
Article in Lipids in health and disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Association between MTTP genotype (-493G/T) polymorphism and hepatic steatosis in hepatitis C: a systematic review and meta-analysis.Lipids in health and disease · 2023Pooled it
- HBV/HCV coinfection and anti-tuberculosis drug-induced liver injury: from risk assessment and exploration of mechanisms to preventive considerations.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Review
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- AMPK-Orchestrated Metabolic Reprogramming in Some Flavivirus Infections: Mechanisms and Therapeutic Opportunities.Viruses · 2026Review
- Virus infections and cancers: from mechanisms to therapeutics.Molecular biomedicine · 2026Review
- Article
- The implications of FASN in viral infection and related diseases: a promising target in antiviral therapies.Frontiers in cellular and infection microbiology · 2026Review
- Qingyi Decoction Alleviates Alcoholic Pancreatitis by Improving Glycerolipid Homeostasis via the AMPK/SREBP-1c/PPARα Pathway.Journal of inflammation research · 2026Article
- Review
- Cigarette Smoke Contributes to the Progression of MASLD: From the Molecular Mechanisms to Therapy.Cells · 2025Review
- Induction of phospholipase A2 group 4C by HCV infection regulates lipid droplet formation.JHEP reports : innovation in hepatology · 2025Article
- Nidogen 2 Overexpression Promotes Hepatosteatosis and Atherosclerosis.International journal of molecular sciences · 2024Article
- LKB1 suppresses KSHV reactivation and promotes primary effusion lymphoma progression.Journal of virology · 2024Article
- A promising anti-tumor targeting on ERMMDs mediated abnormal lipid metabolism in tumor cells.Cell death & disease · 2024Review
- The implications of FASN in immune cell biology and related diseases.Cell death & disease · 2024Review
- Hepatitis C virus non-structural proteins modulate cellular kinases for increased cytoplasmic abundance of host factor HuR and facilitate viral replication.PLoS pathogens · 2023Article
- Metabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells.Journal of neuroinflammation · 2023Article
- Article
- Review
- Review
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundSteatosis is an important clinical manifestation associated with chronic hepatitis C virus (HCV) infection. AMP-activated protein kinase (AMPK), a major mediator of lipid metabolism, regulates HCV-associated hepatic steatosis, but the underlying mechanisms remain obscure. Here we investigated the mechanism of HCV nonstructural protein 5A (NS5A)-induced lipid accumulation by the AMPK/SREBP-1c pathway.
methodsWe generated model mice by injecting recombinant lentiviral particles expressing the NS5A protein (genotype 3a) via the tail vein. The serum levels of alanine aminotransferase (ALT), free fatty acids (FFAs) and triglycerides (TG) were examined. H&E and Oil Red O staining were used to examine lipid droplets. Immunohistochemistry staining, quantitative real-time PCR and Western blotting were used to determine the expression of lipogenic genes.
resultsOur results showed that the serum levels of ALT, FFAs and TG, as well as the accumulation of hepatic lipid droplets, were increased significantly in mice infected with NS5A-expressing lentiviral particles. NS5A inhibited AMPK phosphorylation and increased the expression levels of sterol regulatory element binding protein-1c (SREBP-1c), acetyl-coenzyme A carboxylase 1 (ACC1) and fatty acid synthase (FASN) in vivo and in vitro. Further investigation revealed that pharmacological activation or ectopic expression of AMPK neutralized the upregulation of SREBP-1c, ACC1 and FASN, and ameliorated hepatic lipid accumulation induced by NS5A. Ectopic expression of SREBP-1c enhanced NS5A-induced hepatic lipid accumulation, which was dramatically reversed by pharmacological activation of AMPK.
conclusionsCollectively, we demonstrate that NS5A induces hepatic lipid accumulation via the AMPK/SREBP-1c pathway.
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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.