학술논문
Inflammation‐induced cholestasis in cancer cachexia
Document Type
article
Author
Morgane M. Thibaut; Martina Sboarina; Martin Roumain; Sarah A. Pötgens; Audrey M. Neyrinck; Florence Destrée; Justine Gillard; Isabelle A. Leclercq; Guillaume Dachy; Jean‐Baptiste Demoulin; Anne Tailleux; Sophie Lestavel; Marialetizia Rastelli; Amandine Everard; Patrice D. Cani; Paolo E. Porporato; Audrey Loumaye; Jean‐Paul Thissen; Giulio G. Muccioli; Nathalie M. Delzenne; Laure B. Bindels
Source
Journal of Cachexia, Sarcopenia and Muscle, Vol 12, Iss 1, Pp 70-90 (2021)
Subject
Language
English
ISSN
2190-6009
2190-5991
2190-5991
Abstract
Abstract Background Cancer cachexia is a debilitating metabolic syndrome contributing to cancer death. Organs other than the muscle may contribute to the pathogenesis of cancer cachexia. This work explores new mechanisms underlying hepatic alterations in cancer cachexia. Methods We used transcriptomics to reveal the hepatic gene expression profile in the colon carcinoma 26 cachectic mouse model. We performed bile acid, tissue mRNA, histological, biochemical, and western blot analyses. Two interventional studies were performed using a neutralizing interleukin 6 antibody and a bile acid sequestrant, cholestyramine. Our findings were evaluated in a cohort of 94 colorectal cancer patients with or without cachexia (43/51). Results In colon carcinoma 26 cachectic mice, we discovered alterations in five inflammatory pathways as well as in other pathways, including bile acid metabolism, fatty acid metabolism, and xenobiotic metabolism (normalized enrichment scores of −1.97, −2.16, and −1.34, respectively; all Padj