FXR agonists as therapeutic agents for non-alcoholic fatty liver disease.

Curr Atheroscler Rep

Division of Gastroenterology, University of Pennsylvania, 421 Curie Boulevard, 907 Biomedical Research Building, Philadelphia, PA, 19104, USA,

Published: April 2015

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and a risk factor for both cardiovascular and hepatic related morbidity and mortality. The increasing prevalence of this disease requires novel therapeutic approaches to prevent disease progression. Farnesoid X receptors are bile acid receptors with roles in lipid, glucose, and energy homeostasis. Synthetic farnesoid X receptor (FXR) agonists have been developed to specifically target these receptors for therapeutic use in NAFLD patients. Here, we present a review of bile acid physiology and how agonism of FXR receptors has been examined in pre-clinical and clinical NAFLD. Early evidence suggests a potential role for synthetic FXR agonists in the management of NAFLD; however, additional studies are needed to clarify their effects on lipid and glucose parameters in humans.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11883-015-0500-2DOI Listing

Publication Analysis

Top Keywords

fxr agonists
12
non-alcoholic fatty
8
fatty liver
8
liver disease
8
bile acid
8
lipid glucose
8
fxr
4
agonists therapeutic
4
therapeutic agents
4
agents non-alcoholic
4

Similar Publications

Metabolic dysfunction-associated steatohepatitis (MASH) is a complex disease driven by diverse metabolic and inflammatory pathways. Farnesoid X receptor (FXR) is a promising target for MASH due to its role in bile acid and lipid metabolism, while HSD17B13 regulates liver lipid droplet homeostasis. However, the existing HSD17B13 inhibitors have several druglike property challenges due to the common phenolic structure, a key pharmacophore for the HSD17B13 inhibitor.

View Article and Find Full Text PDF

Obesity due to excessive body fat accumulation remains a global problem. Patients with obesity have high cortisol levels, and its dysregulation is caused by increased 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) levels. The effects and mechanism of J2H-1702, an 11β-HSD1 inhibitor, on nonalcoholic steatohepatitis (NASH) were explored.

View Article and Find Full Text PDF

Background And Aims: Several randomized clinical trials have been conducted assessing the potential efficacy of Farnesoid X receptor (FXR) agonists in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). A comprehensive review and analysis were needed to evaluate the findings of these trials. Hence, this systematic review and meta-analysis aim to study the association between FXR agonists and hepatic outcomes in patients with MASLD.

View Article and Find Full Text PDF

This study investigated whether the galactooligosaccharide (GOS)-metabolism-related genes (GOS-cluster) in contribute to alleviating glucose and lipid metabolic disorders in type 2 diabetic mice. Genomic analysis of 69 strains based on the GOS-cluster, combined with in vitro fermentation experiments, revealed that high-GOS-cluster strains (≥24 MFS, ≥39 GOS-cluster) demonstrated superior GOS utilization and bile salt tolerance. In vivo the high-GOS-cluster strains resulted in a significant reduction of blood glucose levels by 18.

View Article and Find Full Text PDF

FXR-ApoC2 pathway activates UCP1-mediated thermogenesis by promoting the browning of white adipose tissues.

J Biol Chem

January 2025

Department of Science in Korean Medicine, Graduate School, Kyung Hee University, 02447, Seoul, Korea; Department of Pharmacology, College of Korean Medicine, Kyung Hee University, 02447, Seoul, Korea; Kyung Hee Institute of Convergence Korean Medicine, Kyung Hee University, 02447, Seoul, Korea. Electronic address:

FXR, encoded by Nh1r4, is a nuclear receptor crucial in regulating bile acid, lipid, and glucose metabolism. Prior research has indicated that activating FXR in the liver and small intestine may offer protection against obesity and metabolic diseases. This study demonstrates the essential role of the FXR-ApoC2 pathway in promoting the browning of white adipose tissue (WAT).

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!