目的:本研究调查了饮食蛋氨酸限制(MR)对瘦素缺乏型ob/ob小鼠确定的肝脂肪变性进展的影响。
方法:10周龄ob/ob小鼠饲喂含有0.86%(对照饲喂;CF)或0.12%甲硫氨酸(MR)的饮食14周。14周时,切除肝脏和脂肪,收集血液进行分析.在另一项研究中,收集血液以确定体内甘油三酯(TG)和极低密度脂蛋白(VLDL)的分泌率。进行肝组织学检查以确定脂肪变性的严重程度。肝TG,游离脂肪酸水平,还测量了脂肪酸氧化(FAO)。通过定量PCR分析基因表达。
结果:MR逆转了ob/ob小鼠脂肪变性的严重程度。这伴随着体重减轻,尽管类似的重量特异性食物摄取。与CF组相比,肝脏TG水平显着降低响应MR,但脂肪组织重量没有下降。MR降低胰岛素和HOMA比率,但增加总脂联素和高分子量脂联素水平。Scd1基因表达显著下调,而Acadvl,Hadha,而Hadhb在MR中上调,与β-羟基丁酸酯水平增加和FAO增加的趋势相对应。MR小鼠的VLDL分泌率也显著增加,ApoB和Mttp的mRNA水平。炎症标志物的表达,如Tnf-α和Ccr2,也被MR下调。
结论:我们的数据表明,MR通过促进FAO逆转ob/ob小鼠肝脏的脂肪变性,增加脂质的出口,减少肥胖相关的炎症反应。
OBJECTIVE: This study investigated the effects of dietary methionine restriction (MR) on the progression of established hepatic steatosis in the leptin-deficient ob/ob mouse.
METHODS: Ten-week-old ob/ob mice were fed diets containing 0.86% (control-fed; CF) or 0.12% methionine (MR) for 14 weeks. At 14 weeks, liver and fat were excised and blood was collected for analysis. In another study, blood was collected to determine in vivo triglyceride (TG) and very-low-density lipoprotein (VLDL) secretion rates. Liver histology was conducted to determine the severity of steatosis. Hepatic TG, free fatty acid levels, and fatty acid oxidation (FAO) were also measured. Gene expression was analyzed by quantitative PCR.
RESULTS: MR reversed the severity of steatosis in the ob/ob mouse. This was accompanied by reduced body weight despite similar weight-specific food intake. Compared with the CF group, hepatic TG levels were significantly reduced in response to MR, but adipose tissue weight was not decreased. MR reduced insulin and HOMA ratios but increased total and high-molecular-weight adiponectin levels. Scd1 gene expression was significantly downregulated, while
Acadvl, Hadha, and Hadhb were upregulated in MR, corresponding with increased β-hydroxybutyrate levels and a trend toward increased FAO. The VLDL secretion rate was also significantly increased in the MR mice, as were the mRNA levels of ApoB and Mttp. The expression of inflammatory markers, such as Tnf-α and Ccr2, was also downregulated by MR.
CONCLUSIONS: Our data indicate that MR reverses steatosis in the ob/ob mouse liver by promoting FAO, increasing the export of lipids, and reducing obesity-related inflammatory responses.