ArticlePloS one2018
Gemcabene downregulates inflammatory, lipid-altering and cell-signaling genes in the STAM™ model of NASH.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
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- Therapeutic Targets and Approaches to Manage Inflammation of NAFLD.Biomedicines · 2025Review
- New Insights Into the Treatment of Hyperlipidemia: Pharmacological Updates and Emerging Treatments.Cureus · 2024Review
- Zaluzanin C Alleviates Inflammation and Lipid Accumulation in Kupffer Cells and Hepatocytes by Regulating Mitochondrial ROS.Molecules (Basel, Switzerland) · 2023Article
- A Systematic Review of the Randomized Controlled Trials of Gemcabene and Its Therapeutic Uses.Cureus · 2023Review
- An update on animal models of liver fibrosis.Frontiers in medicine · 2023Review
- Screening for Lipid-Metabolism-Related Genes and Identifying the Diagnostic Potential of ANGPTL6 for HBV-Related Early-Stage Hepatocellular Carcinoma.Biomolecules · 2022Article
- Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH).Signal transduction and targeted therapy · 2022Review
- Pharmacotherapy for Non-Alcoholic Fatty Liver Disease: Emerging Targets and Drug Candidates.Biomedicines · 2022Review
- Mouse models of nonalcoholic fatty liver disease (NAFLD): pathomechanisms and pharmacotherapies.International journal of biological sciences · 2022Review
- Therapeutic targets, novel drugs, and delivery systems for diabetes associated NAFLD and liver fibrosis.Advanced drug delivery reviews · 2021Review
- Review
- Knockout of sulfatase 2 is associated with decreased steatohepatitis and fibrosis in a mouse model of nonalcoholic fatty liver disease.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Design and in vivo activity of APurinergic signalling · 2020Article
- Hepatoprotective Effects ofJournal of clinical and experimental hepatologyArticle
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsNon-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) can advance, if untreated, to liver fibrosis, cirrhosis, hepatocellular carcinoma, liver failure and liver-related death. In the United States, NASH affects approximately 2-5% of the population and an additional 10-30% have NAFLD. The number of drugs in development for NASH is growing steadily, along with nonclinical models to support prediction of clinical success. Here we evaluate gemcabene, a first-in-class clinical candidate for dyslipidemia, for its potential utility, based on its combined lipid-lowering and anti-inflammatory efficacy in clinical trials, in a preclinical model of NASH.
methodsGemcabene was evaluated in the STAM™ murine model of NASH. Gemcabene intervention in mice made diabetic with streptozotocin and fed a high fat high-caloric diet was assessed for changes in plasma, and hepatic histological and mRNA markers of lipid metabolism and inflammation.
resultsGemcabene significantly downregulated hepatic mRNA markers of inflammation (TNF-α, MCP-1, MIP-1β, CCR5, CCR2, NF-κB), lipogenesis and lipid modulation (ApoC-III, ACC1, ADH-4, Sulf-2), and fibrosis (TIMP-1 and MMP-2). These effects are important for the prevention of steatosis, inflammation, and hepatocyte ballooning (i.e., the components of the NAFLD Activity Score or NAS), and inhibition of fibrosis progression, and were observed following treatment with gemcabene.
conclusionsThese non-clinical findings corroborate with existing clinical data to support the clinical evaluation of gemcabene as a potential new treatment for NASH.
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