1 research outputs found
Effect of <i>Trichinella spiralis</i>-Derived Antigens on Nonalcoholic Fatty Liver Disease Induced by High-Fat Diet in Mice
Nonalcoholic
fatty liver disease (NAFLD) is a liver disease characterized
by hepatic steatosis, inflammation, and fibrosis, as well as gut dysbiosis.
No approved effective therapeutic medicine is available to date for
NAFLD. Helminth therapy is believed to be a novel direction and therapeutic
strategy for NAFLD. Our previous study showed that Trichinella spiralis-derived antigens (TsAg) had the potential for partially alleviating obesity via regulating
gut microbiota. However, the effect of TsAg on NAFLD
remains unclear. In this study, high-fat diet (HFD)-induced model
mice were treated with TsAg and microbiota transplantation
experiments, and alterations in the pathogenesis of nonalcoholic liver
disease were assessed. The results showed that TsAg markedly reduced hepatic steatosis, improved insulin resistance,
and regulated the abnormal expression of hepatic lipid-related genes.
Of note, TsAg ameliorated hepatic inflammation by
decreasing pro-inflammatory TNF-α and IL-1β, suppressing
hepatic macrophage infiltration, as well as promoting M2 macrophage
polarization. Moreover, TsAg reversed gut dysbiosis,
as especially indicated by an increase in beneficial bacteria (e.g., Akkermansiaceae and Rikenellaceae). Furthermore,
our study found that TsAg reduced LPS hepatic translocation
and hepatic TLR4/NF-κB signaling, which further contributed
to inhibiting hepatic inflammation. In addition, TsAg inhibited hepatic oxidative stress involving Nrf2/NQO-1 signaling.
Microbiota transplantation showed that TsAg-altered
microbiota is sufficient to confer protection against NAFLD in HFD-induced
mice. Overall, these findings suggest that TsAg involving
gut–liver axis and Nrf2/NQO-1 signaling is a novel promising
candidate for NAFLD treatment. TsAg restores intestinal
microbiota and intestinal barrier to inhibit bacteria and LPS translocation
into the liver, contributing to reduce inflammation, oxidative stress,
and hepatic steatosis in the liver of NAFLD mice. The effects were
attributed to, at least in part, the inactivation of NF-κB pathway
and the activation of Nrf-2/NQO-1 pathway. This study provides new
insights for understanding immune modulation by T.
spiralis-derived products as well as the potential
application of TsAg as a modality for NAFLD