ArticleScientific reports2022
FASN inhibition targets multiple drivers of NASH by reducing steatosis, inflammation and fibrosis in preclinical models.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 2 of them syntheses that pooled it.
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Who cites it
60 citing papers in PubMed, 2 syntheses or guidelines pooled it, 92 citations in OpenAlex.
- Efficacy of pharmacotherapies in improving liver fibrosis among patients with MASLD and fibrosis stages of F1-F3: systematic review and network meta-analysis.Journal of translational medicine · 2026Pooled it
- Polyphenol Intervention Ameliorates Non-Alcoholic Fatty Liver Disease: An Updated Comprehensive Systematic Review.Nutrients · 2024Pooled it
- Endothelial cell LGR4 maintains liver sinusoidal endothelial cell Identity and protects against hepatic steatosis.Life sciences · 2026Article
- Cigarette smoke induces FASN-dependent fatty acid metabolic rewiring to drive bladder cancer progression.Cancer letters · 2026Article
- Review
- Fatty acid-activated proton transporter SR4 prevents hepatic steatosis and metabolic alterations in diabetic mice by improving mitochondria function, energy balance and oxidative stress.Experimental and therapeutic medicine · 2026Article
- A potential therapeutic effect of 84-B10 in MASLD through promotion of FASN degradation.Acta pharmacologica Sinica · 2026Article
- Fatty Acid Metabolism in Health and Cancer: From Fundamental Mechanisms to Therapeutic Application.MedComm · 2026Review
- FASN Inhibition Enhances the Efficacy of Chemotherapy in Colorectal Cancer by Inhibiting the DNA Damage Response.Cancer research · 2026Article
- Hepatic glutathione depletion ameliorates MASLD through selective protein oxidation and inhibition of lipogenesis.The Journal of clinical investigation · 2026Article
- Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models.Nature reviews. Gastroenterology & hepatology · 2026Review
- Incretin and Glucagon Signalling in MASLD and MASH: Integrating Metabolic Pathways With Disease Progression.Diabetes, obesity & metabolism · 2026Review
- Protein lactylation in metabolic dysfunction-associated steatotic liver disease: a mechanistic review.Diabetology & metabolic syndrome · 2026Review
- Lipid Droplets in Cancer: New Insights and Therapeutic Potential.International journal of molecular sciences · 2026Review
- The regulatory roles and therapeutic strategies of the solute carrier transporters in cancer metabolism.NPJ precision oncology · 2026Review
- Targeting PKLR and lipogenic enzymes through JNK inhibition to develop a therapeutic strategy for MASLD and MASH.Frontiers in pharmacology · 2026Article
- Fatty acid synthesis promotes mtDNA release via ETS1-mediated oligomerization of VDAC1 facilitating endothelial dysfunction in sepsis-induced lung injury.Cell death and differentiation · 2025Article
- Molecular mechanisms in MASLD/MASH-related HCC.Hepatology (Baltimore, Md.) · 2025Review
- Using Machine Learning for the Discovery and Development of Multitarget Flavonoid-Based Functional Products in MASLD.Molecules (Basel, Switzerland) · 2025Article
- MASH: the nexus of metabolism, inflammation, and fibrosis.The Journal of clinical investigation · 2025Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Fatty acid synthase (FASN) is an attractive therapeutic target in non-alcoholic steatohepatitis (NASH) because it drives de novo lipogenesis and mediates pro-inflammatory and fibrogenic signaling. We therefore tested pharmacological inhibition of FASN in human cell culture and in three diet induced mouse models of NASH. Three related FASN inhibitors were used; TVB-3664, TVB-3166 and clinical stage TVB-2640 (denifanstat). In human primary liver microtissues, FASN inhibiton (FASNi) decreased triglyceride (TG) content, consistent with direct anti-steatotic activity. In human hepatic stellate cells, FASNi reduced markers of fibrosis including collagen1α (COL1α1) and α-smooth muscle actin (αSMA). In CD4+ T cells exposed to NASH-related cytokines, FASNi decreased production of Th17 cells, and reduced IL-1β release in LPS-stimulated PBMCs. In mice with diet induced NASH l, FASNi prevented development of hepatic steatosis and fibrosis, and reduced circulating IL-1β. In mice with established diet-induced NASH, FASNi reduced NAFLD activity score, fibrosis score, ALT and TG levels. In the CCl4-induced FAT-NASH mouse model, FASN inhibition decreased hepatic fibrosis and fibrosis markers, and development of hepatocellular carcinoma (HCC) tumors by 85%. These results demonstrate that FASN inhibition attenuates inflammatory and fibrotic drivers of NASH by direct inhibition of immune and stellate cells, beyond decreasing fat accumulation in hepatocytes. FASN inhibition therefore provides an opportunity to target three key hallmarks of NASH.
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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.