Meanwhile in rats with NAFLD: i) metformin inhibited hepatic total cholesterol and TGF-β, increased diarrhea frequency, and slightly decreased liver steatosis, and fibrosis; ii) 4-hydroxychalcone decreased IL-6, TNF-α and TGF-β, increased IL-10, and markedly decreased liver steatosis and fibrosis; and iii) co-treatment markedly decreased food intake, total caloric intake, and body weight, increased diarrhea; increased IL-10, showing and intermediate effect on decrease TNF-α, TGF-β, liver steatosis and fibrosis.
Both liver tissue and blood samples were processed to evaluate steatosis and NASH changes in histology (Oil Red, Sirius Red and H&E); presence of endothelial damage (CD31, Moesin/p-Moesin, Akt/p-Akt, eNOS/p-eNOS), oxidative stress (iNOS) and fibrosis (αSMA, Col1, PDGF, VEGF) proteins in liver tissue; and inflammatory (IL6, IL10, MCP-1, IL17α, TNFα), liver biochemical function, and hormonal (leptin, ghrelin, visfatin and insulin) alterations in plasma.
Furthermore, NK cell depletion in Jα18<sup>-/-</sup> or IL-10<sup>-/-</sup> mice caused more severe hepatosteatosis, implying NK cells are the direct effector cells to inhibit liver steatosis.
The interaction of HOMA2-IR and IL10 was consistent in both races whereas for LEPR and TGF-beta1 the interactions were statistically significant in only one of the racial groups.These results could imply that some IL10,LEPR and TGF-beta1 polymorphisms may modify an association between steatosis and IR.