目的 探讨不同脂肪供能比例能量限制膳食干预对肥胖大鼠脂质沉积及腹股沟白色脂肪组织基因表达的影响。方法 采用50只7~8 w龄SPF级雄性Wistar大鼠,按体重随机分5组（n=10）,对照组（ND-AL,10% F）给予基础饲料,其余四组均喂饲高脂饲料以建立肥胖动物模型。造模10 w后,肥胖大鼠进一步分成高脂模型组（HF-AL,45% F）,低脂能量限制（LF-CR,10% F+30% CR）、中脂能量限制（MF-CR,36% F+30% CR）和高脂能量限制（HF-CR,46% F+30% CR）组。第20 w处死大鼠,收集血清及脂肪组织备用。结果 HF-AL组大鼠的体重、白色脂肪细胞面积、餐后2 h血糖值以及葡萄糖曲线下面积（AUCG）均显著高于ND-AL组（P<0.05）。不同能量限制组大鼠的体重、肾周脂肪系数、皮下及内脏白色脂肪细胞大小均显著低于HF-AL组（P<0.05）。HF-CR组在能量限制三组中最先出现体重降低现象,腹股沟脂肪系数降低也较其他两组更为显著（P<0.05）。LF-CR组大鼠血清甘油三酯（TG）和总胆固醇（TC）水平、餐后30 min血糖值和AUCG结果显著低于HF-AL组（P<0.05）。腹股沟白色脂肪测序结果进行WGCNA分析,将所有基因共聚为8个模块,其中Brown模块基因与血清TG水平呈显著正相关（P<0.01, r=0.80）,Darkorange2模块与HOMA-IR水平呈显著负相关（P<0.01, r=0.80）。Brown模块潜在枢纽（hub）基因为UBA52,其表达量在HF-CR组中有显著升高的趋势。而Darkorange2模块的潜在hub基因是ITGB3,在MF-CR组中有显著升高的趋势。Darkorange2模块中许多与糖脂代谢相关的基因（SLC2A1、INSR、PRKCZ、ACACB、FASN、SUCLG2、ACSS2、HADH、ACADL和STARD3）与三个CR组大鼠表型具有相关性。结论 不同脂肪供能比能量限制干预均可降低肥胖大鼠体重及脂肪组织重量,但在调节糖脂代谢及皮下脂肪组织特异性基因转录上存在差异。
Abstract
Objective To investigate effects of calorie-restricted diets differing in macronutrient composition on lipid deposition and gene expression in inguinal white adipose tissue in obese rats. Methods A total of 50 male SPF Wistar rats aged 7-8 weeks were used in this study. They were randomly divided into 5 groups (n=10): a control group (ND-AL, 10% fat) receiving a standard diet, and four other groups fed a high-fat diet to induce obesity. After 10 weeks of modeling, obese rats were further divided into the high-fat model group (HF-AL, 45% fat), low-fat calorie-restricted group (LF-CR, 10% fat + 30% CR), medium-fat calorie-restricted group (MF-CR, 36% fat+30% CR), and high-fat calorie-restricted group (HF-CR, 46% fat + 30% CR). At the end of the 20th week, the rats were euthanized, and serum and adipose tissue samples were collected for subsequent analysis. Results The body weight, white adipocyte area, postprandial 2-hour blood glucose level, and area under the glucose curve (AUCG) of the HF-AL group rats were significantly higher than those of the ND-AL group (P<0.05). Rats in the different calorie-restricted groups showed significantly lower body weight, perirenal fat coefficient, and adipocyte size in subcutaneous and visceral white adipose tissues compared to the HF-AL group (P<0.05). Among the three calorie-restricted groups, the HF-CR group exhibited the earliest reduction in body weight, and the reduction in inguinal fat coefficient was more significant than the other two groups (P<0.05). Serum triglyceride (TG) and total cholesterol (TC) levels, postprandial 30-minute blood glucose level, and AUCG in the LF-CR group were significantly lower than those in the HF-AL group (P<0.05). WGCNA analysis of the inguinal white adipose tissue transcriptome classified the clustering of genes into 8 modules. The Brown module genes showed a significant positive correlation with serum TG levels (P<0.01, r=0.80), while the Darkorange2 module showed a significant negative correlation with HOMA-IR levels (P<0.01, r=0.80). The potential hub gene in the Brown module was UBA52, which showed a significant increase in expression in the HF-CR group. The potential hub gene in the Darkorange2 module was ITGB3, which showed a significant increase in expression in the MF-CR group. Many genes related to glucose and lipid metabolism in the Darkorange2 module (SLC2A1、INSR、PRKCZ、ACACB、FASN、SUCLG2、ACSS2、HADH、ACADL and STARD3) were correlated with the phenotypes of the three calorie-restricted groups. Conclusion Interventions by different caloric restrictions decrease body weight and adipose tissue weight in obese rats, but the changes of glucose and lipid metabolism, as well as the transcriptomes of the subcutaneous adipose tissue are significantly different.
关键词
肥胖 /
能量限制 /
宏量营养素 /
转录组学 /
大鼠
Key words
obesity /
caloric restriction /
macronutrients /
transcriptomics /
rat
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基金
福建省自然科学基金项目（No.2022J01237）; 福建医科大学高层次人才科研启动经费（No.XRCZX2017002）
