| Summary: | 碩士 === 國立中興大學 === 生命科學系所 === 103 === Non-alcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease in many countries. Fatty liver disease is divided into two types, including alcohol-related fatty liver disease and non-alcoholic fatty liver disease. In recent years, people changes eating habits and popularity of bubble tea. High fructose intake has been suggested to be a key factor that induces non-alcoholic fatty liver disease. Kefir, a fermented milk product composed of microbial symbionts, has demonstrated numerous biological activities including antibacterial, antioxidant, anti-tumor and immunostimulating effects. But there have no reports to investigate kefir for health of non-alcoholic fatty liver and possible molecular mechanism. The first part of this experiment, 30% fructose solution induced fatty liver in C57BL/6J mice. Group divided into seven groups: (1) Normal: H2O drinking water; (2) Mock: H2O + 30% fructose; (3) KL; low-dose kefir (50 mg/kg) + 30% fructose; (4) KM: medium-dose kefir (100 mg/kg) + 30% fructose; (5) KH: high-dose kefir (150 mg/kg) + 30% fructose; (6) IKM: medium-dose intermediate kefir (150 mg/kg) + 30% fructose; (7) CFM: commercial fermented milk (100mg/kg) + 30% fructose. The second part of experiment, using C57BL/6-Lepob/ob knockout mice as a NAFLD animal model, experimental designs were divided into four groups: (1) Normal: wild type mice＋H2O; (2) Mock: ob/ob mice + H2O; (3) KM: ob/ob mice + medium dose kefir (100 mg/kg) ; (4) KH; ob/ob mice + high dose kefir (150 mg/kg). To elucidate the kefir may play a role of protective mechanisms in NAFLD. The data demonstrated that kefir improved fatty liver syndrome by decreasing body weight, serum ALT, triglyceride, insulin, and hepatic triglyceride, cholesterol and free fatty acid and inflammatory cytokines (TNF-α, IL-6 and IL-1β), In addition, kefir markedly increased phosphorylation of JAK2, improving insulin sensitivity, and enhanced the phosphorylation of AMPK and its targeting enzymes, ACC and SREBP-1c, to down-regulate de novo lipogenesis and stimulation of fatty acid oxidation. At the same time, JAK2 stimulated of STAT3 phosphorylation, which can translocate to the nucleus, and up-regulation of several genes, including CPT1 involved in fatty acid oxidation. In conclusion, the mechanism by which kefir activation of JAK2 signal transduction through JAK2/STAT3 pathways to improve the NAFLD syndrome in fructose-induced fatty liver disease model and Lepob/ob obesity mouse model.
Keywords: NAFLD, kefir, fructose, ob/ob, AMPK, SREBP-1c, ACC, JAK2/STAT3
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