The deficit in folate and vitamin B12 triggers liver macrovesicular steatosis and inflammation in rats with dextran sodium sulfate-induced colitis.

Fiche publication


Date publication

mai 2020

Journal

The Journal of nutritional biochemistry

Auteurs

Membres identifiés du Cancéropôle Est :
Pr BRONOWICKI Jean-Pierre, Pr GUEANT Jean-Louis, Dr LAGROST Laurent


Tous les auteurs :
Harb Z, Deckert V, Bressenot AM, Christov C, Guéant-Rodriguez RM, Raso J, Alberto JM, de Barros JP, Umoret R, Biroulet LP, Lagrost L, Bronowicki JP, Guéant JL

Résumé

The risks of nonalcoholic 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 lipopolysaccharide, 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 S-adenosyl methionine/S-adenosyl homocysteine (SAM/SAH) ratio. Liver inflammation was evidenced by activation of nuclear factor kappa B (NFκB) pathway and nuclear translocation of NFκB phospho-p65. MDD worsened the increase of interleukin 1-beta (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-1β vs. IL10 and increase of MCP-1 in DSS colitis. Our results suggest evaluating whether IBD patients with MDD and increase of MCP-1 are at higher risk of NASH.

Mots clés

Folate, Inflammatory bowel disease, Monocyte chemoattractant protein 1 (MCP-1), Nonalcoholic steatohepatitis, Vitamin B12

Référence

J. Nutr. Biochem.. 2020 May 20;84:108415