Whole hepatic transcriptomic analysis of C26 cachectic mice treated or not with cholestyramine
We found out that bile acid pathways were deeply altered in cachectic mice bearing ectopic tumor, leading to an increase in portal and liver conjugated bile acid levels. Counteracting this increased level in conjugated bile acids using cholestyramine, a bile acid sequestrant, reduced hepatic inflammation in cachectic mice with no impact on steatosis and minor effects on thermogenesis. Hepatic whole transcriptome analysis identified 16 pathways altered in cachectic mice which were counteracted by cholestyramine, pointing out the large contribution of bile acids to hepatic disturbances occurring in cancer cachexia. Overall design: Hepatic mRNA profiles of sham-injected mice (CT), untreated C26-transplanted mice (C26) and C26-injected mice receiving cholestyramine in their diet (C26-CHO) (2% w/w in their diet, from day 1 to 10 after cell injection) (N=8).