Therefore, we investigated the molecular mechanism of steatosis and the role of mitogen-activated protein kinase (MAPK)/toll-like receptor 4-related protein (TLR4) expression in this study.
Genetic and pharmacological suppression of the LPS-TLR4 pathway or transplantation with Tlr4<sup>-/-</sup> bone-marrow-derived hematopoietic cells increases beige fat development and ameliorates diet-induced fatty liver, while Tlr4<sup>-/-</sup> or microbiota-depleted mice are resistant to further CR-stimulated metabolic alterations.
Methionine-choline-deficient mice given 5% fructo-oligosaccharides exhibited significantly decreased hepatic steatosis (p = 0.003), decreased liver inflammation (p = 0.005), a decreased proportion of CD14-positive Kupffer cells (p = 0.01), decreased expression of TLR4 (p = 0.04), and increases in fecal short-chain fatty acid and IgA concentrations (p < 0.04) compared with the findings in methionine-choline-deficient mice that were not administered this prebiotic.
Recent reports have suggested that PNPLA3, IL28B and TLR4-associated single nucleotide polymorphisms (SNPs) may have an impact on hepatic steatosis or fibrosis in patients with chronic HCV infection.
All of these findings demonstrated that BA or BT might ameliorate acute ethanol-induced fatty liver via TLR4 and STAT3 in vivo and in vitro, promising agents for ethanol-induced fatty liver therapies.
Liver NF-kappaB and AP-1 DNA binding were markedly increased in NASH patients (n = 9; P < 0.05) compared to controls, without significant changes in NAFLD patients with steatosis (n = 8), whereas TLR4 expression was comparable between groups.
Nonalcoholic fatty liver disease in humans is associated with increased plasma endotoxin and plasminogen activator inhibitor 1 concentrations and with fructose intake.
As IRF-3 is downstream from the TLR4 adaptor TIR-domain-containing adapter-inducing IFN-beta (Trif), we demonstrate that macrophages from Trif-/- mice are resistant to this dysregulation of TNF-alpha transcription by EtOH in vitro as well as EtOH-induced steatosis and TNF dysregulation in vivo.