Effect of Concentration and type of Dietary Fatty Acid on Development of Nonalcoholic Fatty Liver Disease

The current study was designed to determine if dietary fatty acid concentration and composition affects the development and progression of nonalcoholic fatty liver disease. Male SD rats were overfed diets low (5%) or high (70%) fat diets via total enteral nutrition where the fat source was olive oil (monounsaturated), or corn oil (polyunsaturated). Overfeeding 5% corn oil produced little steatosis relative to feeding 5% olive oil. This was associated with lower fatty acid synthesis and reduced SREBP-c signaling in the 5% corn oil group. Overfeeding 70% fat diets increased steatosis and lead to increased liver necrosis in the 70% corn oil but not olive oil group. Increased injury after feeding polyunsaturated fat diets was linked to peroxidizability of hepatic free fatty acids and triglycerides and appearance of peroxidaized lipid products HETES and HODES previously linked to clinical nonalcoholic steatohepatitis.本研究旨在探究膳食脂肪酸浓度与组成是否会影响非酒精性脂肪性肝病（nonalcoholic fatty liver disease）的发生与进展。本研究选用雄性SD大鼠，通过全肠内营养方式分别给予脂肪含量为5%（低脂）或70%（高脂）的饲料，脂肪来源分别为橄榄油（单不饱和脂肪酸）与玉米油（多不饱和脂肪酸），并实施过量饲喂。相较于饲喂5%橄榄油饲料的组别，饲喂5%玉米油饲料组仅出现轻微脂肪变性。该现象与5%玉米油组较低的脂肪酸合成水平及减弱的固醇调节元件结合蛋白-c（SREBP-c）信号通路活性相关。过量饲喂70%脂肪含量饲料会加重脂肪变性，且仅在70%玉米油饲料组中引发肝坏死程度升高，橄榄油组未出现该变化。饲喂多不饱和脂肪酸饲料后出现的肝脏损伤加重，与肝脏游离脂肪酸及甘油三酯的过氧化易感性、过氧化脂质产物HETES与HODES的出现相关，上述产物此前已被证实与临床非酒精性脂肪性肝炎（nonalcoholic steatohepatitis）存在关联。