NOD2 in hepatocytes engages a liver-gut axis to protect against steatosis, fibrosis, and gut dysbiosis during fatty liver disease in mice.

NOD2 in hepatocytes engages a liver-gut axis to protect against steatosis, fibrosis, and gut dysbiosis during fatty liver disease in mice. Am J Physiol Endocrinol Metab. 2020 Jun 09;: Authors: Cavallari JF, Pokrajac NT, Zlitni S, Foley KP, Henriksbo BD, Schertzer JD Abstract Obesity promotes non-alcoholic fatty liver disease (NAFLD). The intestinal microbiota contributes to NAFLD progression through a gut to liver pathway that promotes inflammation and fibrosis. Gut microbiota-derived factors can travel to the liver and activate immune responses in liver-resident cells to promote inflammation and NAFLD. Little is known about bacterial sensors or immune responses that can protect against NAFLD. We tested if the bacterial cell wall sensor nucleotide-binding oligomerization domain-containing (NOD)2 protects against diet-induced NAFLD in mice. Whole-body deletion of NOD2 exacerbated liver steatosis and fibrosis in mice fed a NAFLD-promoting diet. Mice with a hepatocyte-specific deletion of NOD2 (Nod2-/-HKO) also had higher liver steatosis and fibrosis compared to littermate wild type mice (WTloxp) fed a NAFLD-promoting diet. Hepatocyte-specific NOD2 deletion altered the composition of the gut microbiome. Nod2-/-HKO mice had increased relative abundance of Clostridiales and lower Erysipelotrichaceae among other changes in cecal bacteria compared to littermate WTloxp mice. Hepatocyte-specific NOD2 deletion altered a transcriptional program...
Source: Am J Physiol Endocri... - Category: Endocrinology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research