Cancers (Basel)
Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy.
Published: June 2022
The Farnesoid X Receptor (FXR) is the master regulator of Bile Acids (BA) homeostasis orchestrating their synthesis, transport and metabolism. Disruption of BA regulation has been linked to gut-liver axis diseases such as colorectal cancer (CRC). In this study, firstly we examined the role of constitutive activation of intestinal FXR in CRC; then we pre-clinically investigated the therapeutic potential of a diet enriched with a synthetic FXR agonist in two models of CRC (chemically-induced and genetic models). We demonstrated that mice with intestinal constitutive FXR activation are protected from AOM/DSS-induced CRC with a significant reduction of tumor number compared to controls. Furthermore, we evaluated the role of chemical FXR agonism in a DSS model of colitis in wild type (WT) and FXR mice. WT mice administered with the FXR activating diet showed less morphological alterations and decreased inflammatory infiltrates compared to controls. The FXR activating diet also protected WT mice from AOM/DSS-induced CRC by reducing tumors' number and size. Finally, we proved that the FXR activating diet prevented spontaneous CRC in APC mice via an FXR-dependent modulation of BA homeostasis. Our results demonstrate that intestinal FXR activation prevented both inflammation- and genetically-driven colorectal tumorigenesis by modulating BA pool size and composition. This could open new avenues for the therapeutic management of intestinal inflammation and tumorigenesis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9265121 | PMC |
http://dx.doi.org/10.3390/cancers14133081 | DOI Listing |
Int J Biol Sci
January 2025
Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
PIEZO1 has been found to play a vital role in regulating intestinal epithelial cells (IEC) function and maintaining intestinal barrier in recent years. Therefore, IEC PIEZO1 might exert a significant impact on liver metabolism through the gut-liver axis, but there is no research on this topic currently. Classic high-fat diet (HFD) model and mice with IEC-specific deficiency of PIEZO1 ( ) were used to explore the problem.
View Article and Find Full Text PDFNature
January 2025
Department of Chemistry and Chemical Biology, Boyce Thompson Institute, Cornell University, Ithaca, NY, USA.
Metabolites derived from the intestinal microbiota, including bile acids (BA), extensively modulate vertebrate physiology, including development, metabolism, immune responses and cognitive function. However, to what extent host responses balance the physiological effects of microbiota-derived metabolites remains unclear. Here, using untargeted metabolomics of mouse tissues, we identified a family of BA-methylcysteamine (BA-MCY) conjugates that are abundant in the intestine and dependent on vanin 1 (VNN1), a pantetheinase highly expressed in intestinal tissues.
View Article and Find Full Text PDFJ Ethnopharmacol
January 2025
Department of Pharmacology, Shaanxi University of Chinese Medicine, No. 1 Middle Section of Century Avenue, Xianyang 712046, People's Republic of China. Electronic address:
Ethnopharmacological Relevance: Dioscorea bulbifera L. (DBL) was a traditional Chinese medicine commonly used to treat goitre and cancer. Nevertheless, its clinical application may lead to liver injury.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Academy of Agriculture and Forestry Sciences, Qinghai University, Xining 810016, China.
Bile acids (BAs), a category of amphiphilic metabolites synthesized by liver cells and released into the intestine via the bile duct, serve a vital role in the emulsification of ingested fats during the digestive process. Beyond their conventional emulsifying function, BAs, with their diverse structures, also act as significant hormones within the body. They are pivotal in facilitating nutrient absorption by interacting with the farnesoid X receptor (FXR), and they serve as key regulators of lipid and glucose metabolism, as well as immune system balance.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
January 2025
Department of Endocrinology, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.
Objective: The objective of this study is to investigate the ability of Ramulus Mori (Sangzhi) alkaloid tablets (SZ-A) to ameliorate obesity and lipid metabolism disorders in rats subjected to a high-fat diet (HFD) through metagenomics, untargeted lipidomics, targeted metabolism of bile acid (BA), and BA pathways, providing a novel perspective on the management of metabolic disorders.
Methods: In this research, HFD-fed rats were concurrently administered SZ-A orally. We measured changes in body weight (BW), blood lipid profiles, and liver function to assess therapeutic effects.
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