Trehalose and Omega-3 Polyunsaturated Fatty Acids Therapy: A Promising New Approach for Non-Alcoholic Fatty Liver Disease

  • 羅 丹儒

Student thesis: Master's Thesis


Background: Non-alcoholic fatty liver disease (NAFLD) is considered as one of the most common causes of chronic liver disease worldwide Therefore the development of new treatment strategies is imperative The use of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have demonstrated in animal models and human clinical trials to improve liver steatosis liver function tests cholesterol and serum triglycerides levels Recently an alpha-linked disaccharide named trehalose showed to prevent NALFD development in an animal model Trehalose inhibits a specific type of glucose transporter in the hepatocyte cell membrane decreasing fructose uptake and subsequently leading to a starvation like environment triggering a cellular autophagy response Purpose: To evaluate individually and in a combined way the use of omega-3 PUFAs and trehalose in the prevention and treatment of NAFLD in a high fructose diet-induced animal model Experimental design: Male Wistar rats (37) were exposed to a high fructose diet (HFrD) 60% for 24 weeks All rats were divided into six experimental groups: normal chow NAFLD model prophylaxis trehalose omega-3 PUFAs and trehalose + omega-3 Normal chow group was exposed to a regular rat diet NAFLD model group was exposed only to HFrD Prophylaxis group was exposed to simultaneous treatment of trehalose and omega-3 PUFAs trehalose since the beginning of the HFrD for sixteen weeks After 16 weeks of HFrD exposure rats were expose to an eight-week treatment with trehalose at a dose of 3 mg/kg/day (trehalose) omega-3 PUFAs at a dose of 2 4 mg/kg/day (omega-3 PUFAs) and combined dosage of trehalose and omega-3 PUFAs (Trehalose + omega-3 PUFAs) Results: The combine use of trehalose and omega-3 PUFAs prevents and reverse NAFLD histological and metabolic features (hyperglycemia insulin resistance hypertriglyceridemia hypercholesterolemia) by a de novo lipogenesis downregulation and a beta oxidation upregulation mediated by the expression of the peroxisome proliferator activated receptor alpha (PPAR-?) and sterol regulatory element binding protein 1c (SREBP-1c) respectively Conclusions: The concomitant use of trehalose and omega-3 PUFAs prevent and reverse histological and metabolic features of NAFLD through a de novo lipogenesis down regulation and a beta oxidation upregulation in a diet-induced animal model
Date of Award2018 Aug 14
Original languageEnglish
SupervisorXi-Zhang Lin (Supervisor)

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