Wang Baogui, Li Lumin, Fu Jing, Yu Ping, Gong Deming, Zeng Cheng, Zeng Zheling
State Key Laboratory of Food Science and Technology, Nanchang Univ, Nanchang, 330047, China.
School of Resource and Environmental and Chemical Engineering, Nanchang Univ, Nanchang, 330031, China.
J Food Sci. 2016 Mar;81(3):H794-800. doi: 10.1111/1750-3841.13210. Epub 2016 Jan 22.
Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity-related metabolic complications, which caused by excess energy intake and physical inactivity apart from genetic defects. The mechanisms that promote disease progression from NAFLD to further liver injury are still unclear. We hypothesize that the progression involved "2nd hit" is strongly influenced by the type of fatty acids in diets. Flow cytometric analysis showed that medium-chain fatty acid (MCFA) markedly decreased the percentage of late apoptotic and necrotic cells compared with long-chain fatty acid (LCFA), and MCFA inhibited the activities of caspase-3 and -9 in human liver cells with steatosis. Western blot analysis found that the levels of inflammatory markers (interleukin [IL]-6, IL-1-β, and tumor necrosis factor-α) were substantially reduced by MCFA compared with LCFA. Proteomic analysis further showed that LCFA inhibited the expression of antioxidant enzymes, and increased the expression of proteins associated with oxidative stress. It was found that LCFA (palmitate), not MCFA induced apoptosis, oxidative stress and chronic inflammatory responses in the hepatic cells with steatosis. In conclusion, reasonable selection of dietary fats has potential to translate therapeutically by ameliorating disease progression in patients with NAFLD.
非酒精性脂肪性肝病（NAFLD）与肥胖相关的代谢并发症密切相关，除了遗传缺陷外，这些并发症是由能量摄入过多和缺乏身体活动引起的。促进疾病从NAFLD进展为进一步肝损伤的机制仍不清楚。我们假设涉及“二次打击”的进展受到饮食中脂肪酸类型的强烈影响。流式细胞术分析表明，与长链脂肪酸（LCFA）相比，中链脂肪酸（MCFA）显著降低了晚期凋亡和坏死细胞的百分比，并且MCFA抑制了脂肪变性人肝细胞中caspase-3和-9的活性。蛋白质印迹分析发现，与LCFA相比，MCFA使炎症标志物（白细胞介素[IL]-6、IL-1-β和肿瘤坏死因子-α）的水平大幅降低。蛋白质组学分析进一步表明，LCFA抑制抗氧化酶的表达，并增加与氧化应激相关蛋白质的表达。研究发现，LCFA（棕榈酸）而非MCFA在脂肪变性的肝细胞中诱导细胞凋亡、氧化应激和慢性炎症反应。总之，合理选择膳食脂肪有可能通过改善NAFLD患者的疾病进展而具有治疗作用。
