ArticlePharmaceutical research2013
Synthetic FXR agonist GW4064 prevents diet-induced hepatic steatosis and insulin resistance.
Article in Pharmaceutical research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02158351 (Role and Pathogenetic Mechanisms of Intestinal Microbiota in Non-alcoholic Fatty Liver Disease Severity in Obese and Non-obese Subjects), which is not on this map. Cited by 95 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Role and Pathogenetic Mechanisms of Intestinal Microbiota in Non-alcoholic Fatty Liver Disease Severity in Obese and Non-obese Subjects
Who cites it
95 citing papers in PubMed, 161 citations in OpenAlex.
- The gut microbiome-bile acid-FXR interplay: a pivotal axis in metabolic and gastrointestinal diseases.Gut microbes · 2026Review
- Effects of the FXR agonist GW4064 on metabolic disorders in db/db mice.Laboratory animal research · 2026Article
- Glycyrrhizin preparations in liver diseases: a narrative review of mechanisms and therapeutic potential.Frontiers in pharmacology · 2026Review
- TIMP1 Derived from Mesenchymal Stem Cells Promotes Bladder Cancer Progression by Regulating the Formation of VDIMs through the RAP1 Pathway.International journal of biological sciences · 2026Article
- Review
- GLP-1 receptor agonism: a transformative approach for managing type-2 diabetes and obesity.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2025Review
- Farnesoid X receptor‑driven metabolic plasticity: Bridging physiological adaptation and malignant transformation in lipid handling (Review).International journal of molecular medicine · 2025Review
- Liver Metabolism at the Crossroads: The Reciprocal Control of Nutrient-Sensing Nuclear Receptors and Autophagy.International journal of molecular sciences · 2025Review
- Different types of bile acids exhibit opposite regulatory effects on lipid metabolism in finishing pigs through bile acid receptors.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- The role of the farnesoid X receptor in diabetes and its complications.Molecular and cellular biochemistry · 2025Review
- Glucagon-like peptide-1 receptor agonists improve metabolic dysfunction-associated steatotic liver disease outcomes.Scientific reports · 2025Article
- The therapeutic effects of dendrobium officinale polysaccharides on diabetes mellitus: from the perspective of gut microbiota.Frontiers in endocrinology · 2025Review
- Dysregulated bile acid homeostasis: unveiling its role in metabolic diseases.Medical review (2021) · 2024Review
- The role of botanical triterpenoids and steroids in bile acid metabolism, transport, and signaling: Pharmacological and toxicological implications.Acta pharmaceutica Sinica. B · 2024Review
- Targeting nuclear receptors for NASH/MASH: From bench to bedside.Liver research (Beijing, China) · 2024Article
- The contributions of bacteria metabolites to the development of hepatic encephalopathy.Liver research (Beijing, China) · 2023Article
- Weight-independent effects of Roux-en-Y gastric bypass surgery on remission of nonalcoholic fatty liver disease in mice.Obesity (Silver Spring, Md.) · 2023Article
- Article
- Precision pharmacological reversal of strain-specific diet-induced metabolic syndrome in mice informed by epigenetic and transcriptional regulation.PLoS genetics · 2023Article
- Gut microbiome determines therapeutic effects of OCA on NAFLD by modulating bile acid metabolism.NPJ biofilms and microbiomes · 2023Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTo examine the effect of farnesoid X receptor (FXR) activation by its synthetic agonist, 3-[2-[2-Chloro-4-[[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methoxy]phenyl]ethenyl]benzoic acid (GW4064) on diet-induced obesity and hepatic steatosis.
methodsFifteen week-old C57BL/6 mice fed with high-fat diet (HFD) or high-fat, high-cholesterol diet were treated by twice weekly injection of GW4064 (50 mg/kg) intraperitoneally or DMSO (carrier solution) for 6 weeks. Body weight, body composition and food intake were monitored weekly. Serum glucose and insulin levels and lipid content in the liver were measured at the end of study. Additionally, genes involved in lipogenesis, gluconeogenesis and inflammation were analyzed by real time PCR. CD36 protein level was detected by western blot.
resultsActivation of FXR by GW4064 suppressed weight gain in C57BL/6 mice fed with either HFD or high-fat and high-cholesterol diet. GW4064 treatment of mice significantly repressed diet-induced hepatic steatosis as evidenced by lower triglyceride and free fatty acid level in the liver. Analysis of genes involved in lipid metabolism showed GW4064 markedly reduced lipid transporter Cd36 gene expression without affecting expression of genes that are directly involved in lipogenesis. GW4064 treatment attenuated hepatic inflammation while having no effect on white adipose tissue. In addition, activation of FXR by GW4064 avoided diet-induced hyperinsulinemia and hyperglycemia through decreasing the transcript levels of phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6pase), two key enzymes in gluconeogenesis.
conclusionsThe results verify the important function of FXR in diet-induced obesity and suggest that FXR agonists are promising therapeutic agents for obesity-associated metabolic disorders.
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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.