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.
Key words
obesity /
caloric restriction /
macronutrients /
transcriptomics /
rat
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