Hepatic XXXX signaling in obese NAFLD.

@entity1 @entity844 @entity21064 @entity2365 @entity1561 @entity209 @entity2939 @entity1718
@entity1561 occurs frequently in the setting of @entity209 , but the factors leading to @entity1561 ( @entity1561 ) are not fully understood. This study investigated @entity2939 ( @entity2939 ) signaling in @entity1 liver with the goal of delineating whether activation of this pathway segregates those with @entity1561 from those with @entity1561 . Experiments were performed using liver biopsy tissue obtained from class III obese subjects undergoing bariatric surgery, and extended to an immortalized @entity1 hepatocyte HepaRG cell line and primary @entity1 hepatocytes. The bacterial endotoxin lipopolysaccharide (LPS) and total free @entity844 levels were significantly increased in plasma of @entity1561 @entity1 . @entity2939 mRNA levels were significantly increased in subjects with @entity1561 compared with NAFL as was @entity21064 in the myeloid differentiation factor 88-independent signaling pathway. In HepaRG cells, nuclear factor-kB (NF-kB) nuclear translocation and functional activity increased following treatment with the @entity844 , @entity2365 , and following exposure to LPS compared with hepatocytes stimulated with a lipogenic treatment that induced de novo lipogenesis. @entity2365 and LPS induction of NF-kB activity was partially attenuated by chemical- or small-interfering RNA-mediated inhibition of @entity2939 . Expression of @entity2939 and its downstream mediators was upregulated with @entity2365 and LPS. Similar results were observed using primary @entity1 hepatocytes from a lean donor. Interestingly, NF-kB activity assays showed obese donor hepatocytes were resistant to chemical @entity2939 inhibition. In conclusion, @entity2939 expression is upregulated in a large cohort of @entity1561 @entity1 , compared with those with NAFL, and this occurs within the setting of increased LPS and @entity1718 .
