| Autor: |
Thibaut MM; Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium., Gillard J; Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium.; Laboratory of Hepato-Gastroenterology, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium., Dolly A; Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium., Roumain M; Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium., Leclercq IA; Laboratory of Hepato-Gastroenterology, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium., Delzenne NM; Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium., Muccioli GG; Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium., Bindels LB; Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium. |
| Abstrakt: |
Bile acids exert diverse actions on host metabolism and immunity through bile acid-activated receptors, including Takeda G protein-coupled receptor 5 (TGR5). We have recently evidenced an alteration in bile acids in cancer cachexia, an inflammatory and metabolic syndrome contributing to cancer death. This current study aims to further explore the links emerging between bile acids and cancer cachexia. First, we showed that bile flow is reduced in cachectic mice. Next, comparing mice inoculated with cachexia-inducing and with non-cachexia-inducing C26 colon carcinoma cells, we demonstrated that alterations in the bile acid pathways and profile are directly associated with cachexia. Finally, we performed an interventional study using ursodeoxycholic acid (UDCA), a compound commonly used in hepatobiliary disorders, to induce bile acid secretion and decrease inflammation. We found that UDCA does not improve hepatic inflammation and worsens muscle atrophy in cachectic mice. This exacerbation of the cachectic phenotype upon UDCA was accompanied by a decreased TGR5 activity, suggesting that TGR5 agonists, known to reduce inflammation in several pathological conditions, could potentially counteract cachectic features. This work brings to light major evidence sustaining the emerging links between bile acids and cancer cachexia and reinforces the interest in studying bile acid-activated receptors in this context. |
