Tyrosol Ameliorates Liver Inflammatory Response in a Mouse Model of Nonalcoholic Fatty Liver Disease (NFALD) by Regulating JAK1/STAT3

Abstract

Nonalcoholic fatty liver disease (NAFLD) is becoming one of the major health issues globally. NAFLD is usually associated with obesity and other metabolic syndromes, and there is no specific cure to address this issue so far. Featured by lipid accumulation in hepatocytes, and later progressing to fibrosis, inflammatory responses are involved in the various levels of the pathological changes. In the present study, we added a natural compound, tyrosol, which in our previous study had demonstrated anti-inflammatory properties, to a high-fat diet-induced NAFLD mouse model and investigated whether tyrosol could mitigate the liver damage by attenuating the inflammation response. The treatment with tyrosol significantly improved the liver function and decreased the fasting glucose level in NAFLD mice. Morphologically, our results showed that tyrosol could reduce the fat deposition and lipid droplets accumulation in liver tissue. The key regulating factors, JAK1 and STAT3, were increased in NAFLD mice, but tyrosol treatment could effectively prevent the upregulation. The expression levels of pro-inflammatory cytokine genes in liver tissue of the NAFLD mice were upregulated, which could be effectively prevented by the treatment with tyrosol. Overall, in the high-fat diet-induced NAFLD mouse model, tyrosol could improve the liver function and, more importantly, ameliorate the inflammatory response triggered by the high-fat diet. Although our data here are consistent with the previous report that tyrosol could exert beneficial effects on the NAFLD animal model, we also provide solid evidence that tyrosol is able to conquer the inflammatory response in liver, which is related to the high-fat-diet feeding. Tyrosol could be a promising candidate for the treatment of NAFLD in the future.