火龙果甜菜红素提取物对肥胖的干预作用及相关机理研究

发布时间：2018-03-26 11:17

本文选题：火龙果　切入点：甜菜红素　出处：《浙江大学》2016年博士论文

【摘要】：肥胖症是指受遗传和生活方式等因素影响,导致能量代谢异常,体内脂肪积累过多和分布异常的一种代谢性综合征,与胰岛素抵抗、糖尿病、高血脂、高血压、脂肪肝与心血管疾病等密切相关。目前大多数减肥方法都存在副作用大与复发率高等缺点。甜菜红素在火龙果中含量很高,是一种已被广泛应用在食品工业中的天然来源的食用色素。甜菜红素具有的较强的清除自由基和抗氧化的生物活性与其抗炎、降低血脂、降血压等生物功能密切相关。因此,从火龙果中提取甜菜红素并研究其对肥胖的干预作用具有重要意义。本课题对红皮白肉火龙果果皮和红肉火龙果果肉中的甜菜红素进行分离鉴定,并通过油酸(OA)孵育HepG2细胞在体外建立肝细胞脂肪变性模型评价火龙果果肉甜菜红素提取物对肝细胞脂质沉积的改善作用,并探讨了自噬在火龙果甜菜红素改善脂质沉积中的作用；通过建立高脂膳食诱导肥胖小鼠模型评价了火龙果果汁、红皮白肉火龙果果皮和红肉火龙果果肉甜菜红素提取物对肥胖及其并发症,如胰岛素抵抗(IR)和非酒精性脂肪肝(NAFLD)的干预作用,并对火龙果甜菜红素提取物对脂质代谢通路和肠道菌群的影响做了初步探究。课题的主要研究结论如下：1.膳食红皮白肉火龙果果汁虽然不能够减轻小鼠体重,但能够显著降低小鼠血清中的甘油三酯(TG)、总胆固醇(TC)以及低密度脂蛋白胆固醇(LDL-C)的含量水平及肝脏中TG和TC的含量水平,改善脂肪肝和脂肪组织肥大,显著降低小鼠血清中葡萄糖和胰岛素水平,改善高脂膳食诱导的胰岛素抵抗,提高肥胖小鼠的胰岛素敏感指数。火龙果果汁能够调控肝脏中脂质代谢和胆固醇代谢相关基因的表达水平,并激活FGF21信号通路。2.红皮白肉火龙果果皮的甜菜红素提取物(PPBN)含有14种甜菜红素组分,红肉火龙果果肉甜菜红素提取物(HPBN)含有12种甜菜红素组分,PPBN与HPBN均有较强的体外抗氧化能力。3.PPBN与HPBN均能够显著降低高脂膳食引起的小鼠体重的增加,降低血清中的甘油三酯(TG)、总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)的含量水平,降低肝脏中TG和TC的含量水平,改善肝组织脂质沉积和脂肪细胞肥大,减轻由高脂膳食诱发的胰岛素抵抗,降低血糖水平,提高肥胖小鼠的葡萄糖耐受性,且PPBN的减重效果优于HPBN。此外,研究发现PPBN可显著改变小鼠肝脏中脂质和胆固醇代谢相关基因的表达水平,改善FGF21抵抗；HPBN可显著改变肥胖小鼠的肠道微生态环境,增大肥胖小鼠的肠道菌群多样性,减小Firmicutes的丰度,增大Bacteroidetes、Proteobacteria和Akkermansia的丰度水平。4.HPBN能显著减少油酸诱导的肝细胞脂质沉积,上调自噬标识蛋白LC3、Beclinl和Atg7的表达水平,促进自噬体的形成。加入3-MA(自噬抑制剂)抑制自噬的发生后,HPBN抑制肝细胞脂质沉积的作用减弱。研究结果表明HPBN能够通过增强HepG2细胞内的自噬水平减少油酸诱导的肝细胞内的脂质沉积。
[Abstract]:Obesity refers to the factors that affected the genetic and lifestyle, leading to abnormal energy metabolism, body fat excessive accumulation and abnormal distribution of a metabolic syndrome, and insulin resistance, diabetes mellitus, hyperlipidemia, hypertension, fatty liver and cardiovascular disease are closely related. At present most weight-loss methods have side effects and recurrence high rate of defects. Beet red pigment in Pitaya content is very high, is a kind of natural source has been widely used in the food industry. The edible pigment of beet red pigment has strong free radical scavenging and antioxidant biological activity and anti-inflammatory, reducing blood fat, lowering blood pressure and other biological functions are closely related. Therefore, the extraction of red beet from pitaya in the prime and the study has important significance for the intervention of obesity. The subject of the Pitaya skin and red red skin and white flesh pitayas in beet red pigment was From the identification, and the oleic acid (OA) were incubated with HepG2 cells to establish hepatic steatosis model to evaluate the effect of red beet pulp pitaya extract on liver lipid deposition in vitro, and to explore the factors to improve the autophagy lipid deposition in the role of Pitaya red beet; through the establishment of high fat diet induced obese mice model evaluation pitaya juice, pitaya pitaya and red meat erythroderma peel pulp beet red pigment extract on obesity and its complications, such as insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD) and the intervention effect of Pitaya beet red pigment extract affects lipid metabolism and intestinal flora to do a preliminary inquiry. Main conclusions the subject is as follows: 1. dietary erythroderma pitaya juice although not can reduce the body weight of mice, but can significantly reduce the serum glycerol ester (TG), total three The cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels of TG and TC levels and the liver, improve fatty liver and adipose tissue hypertrophy, significantly decreased glucose and insulin levels in serum of mice, improve the resistance of high fat diet induced insulin, improve insulin sensitivity index in obese mice. Pitaya juice can the expression level of lipid metabolism and cholesterol metabolism related gene regulation in the liver, and activate the FGF21 signaling pathway.2. erythroderma pitaya peel of red beet extract (PPBN) contains 14 kinds of beet red pigment component, pitaya red pulp beet red pigment extract (HPBN) contains 12 kinds of beet red pigment components, PPBN and HPBN have strong antioxidant ability in vitro of.3.PPBN and HPBN were significantly reduced and increased body weight of mice in high fat diet induced the decrease in serum triglycerides (TG), total cholesterol (TC) and Low density lipoprotein cholesterol (LDL-C) levels, reduce the levels of TG and TC in the liver, improve the liver lipid deposition and fat cell hypertrophy, reduce the insulin resistance induced by high-fat diet, reduce the level of blood glucose, improve glucose tolerance in obese mice, and the weight loss of PPBN is better than HPBN. in addition, research found that PPBN can significantly change the expression levels of lipid and cholesterol metabolism related genes in the liver of mice, improve the resistance of FGF21; HPBN can significantly change the obese mice intestinal micro ecological environment, increase the obese mice intestinal flora diversity, abundance, reduced the increase of Firmicutes Bacteroidetes, Proteobacteria and Akkermansia levels of.4.HPBN can significantly reduce the abundance of liver cells lipid deposition induced by oleic acid, identification of autophagy protein LC3, expression of Beclinl and Atg7, promote the formation of autophagosomes. Adding 3-MA (autophagy After inhibiting the occurrence of autophagy, the effect of HPBN on the inhibition of hepatocyte lipid deposition was weakened. The results showed that HPBN could reduce lipid deposition in oleic acid-induced hepatocytes by enhancing autophagy in HepG2 cells.

【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R151;TS201.4

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