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.
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http://dx.doi.org/10.1007/s11883-015-0500-2 | DOI Listing |
J Med Chem
January 2025
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, P. R. China.
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 PDFEur J Pharmacol
February 2025
College of Korean Medicine, Gachon University, Seongnam, 13120, South Korea. Electronic address:
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 PDFClin Res Hepatol Gastroenterol
January 2025
School of Medicine, Wayne State University, Detroit, MI, USA.
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 PDFJ Agric Food Chem
January 2025
State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, China.
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 PDFJ 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).
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