Abstract
The risks of non-alcoholic steatohepatitis (NASH) and deficiency in vitamin B12 and folate (methyl donor deficiency, MDD) are increased in inflammatory bowel disease (IBD). We investigated the influence of MDD on NASH in rats with DSS induced colitis. Two-month-old male Wistar rats were subjected to MDD diet and/or ingestion of DSS and compared to control animals. We studied steatosis, inflammation, fibrosis, plasma levels of metabolic markers, cytokines and LPS, and inflammatory pathways in liver. MDD triggered a severe macrovesicular steatosis with inflammation in DSS animals that was not observed in animals subjected to DSS or MDD only. The macrovesicular steatosis was closely correlated to folate, vitamin B12, homocysteine plasma level and liver SAM/SAH ratio. Liver inflammation was evidenced by activation of NFκB pathway and nuclear translocation of NFκB phospho-p65. MDD worsened the increase of IL-1β and abolished the increase of IL10 produced by DSS colitis. It increased monocyte chemoattractant protein 1 (MCP-1). MDD triggers liver macrovesicular steatosis and inflammation through imbalanced expression of IL-1 β vs. IL10 and increase of MCP-1, in DSS colitis. Our results suggest to evaluating whether IBD patients with MDD and increase of MCP-1 are at higher risk of NASH.