Gene expression profile from short-term caloric restriction in mouse adipose tissue

To provide a robust understanding of a transcriptomic change by short-term CR at body fat of mice, we applied three serial strengths of CR to mice including 15%, 30%, and 45% reduction of carbon source. Using Affymetrix mouse 1.0 ST array platform, we obtained and analyzed the transcriptome data for significantly changed genes in expression. Here, we identified 446 genes and categorized the genes based on their biological roles. We observed gradual down-regulation of several signaling pathways including insulin/insulin-like growth factor (IGF) 1, epidermal growth factor (EGF), transforming growth factor beta (TGF-β) and canonical Wingless-type mouse mammary tumor virus integration site (Wnt) signaling according to the CR strengths. Many genes related to structural feature including extracellular matrix (ECM), cell adhesion and cytoskeleton were also down-regulated with a strong correlation to the serial CR treatments. Furthermore, genes for cell cycle and adipogenesis were down-regulated. According to previous studies, these are target functions of the aforementioned four signaling pathways. On the other hand, the genes for specific metabolic features including tricarboxylic acid (TCA) cycle and electron transport chain (ETC) exhibited a transcriptional increase. In addition, adipose tissue expansion markers such as leptin, Mesoderm specific transcript (Mest) and Secreted frizzled-related sequence protein 5 (Sfrp5), and most genes for transport and immune response showed a down-regulation by CR. Comparing gene expression profiles to understand transcriptomic changes of adipose tissue by serial strength (15%, 30%, and 45%) of short-term (10 weeks) caloric restriction to young age (18 weeks) mice (n=3 in each group).

为深入阐明小鼠体脂短期热量限制（Caloric Restriction, CR）所诱导的转录组变化，我们对小鼠施加了三种梯度递增的热量限制干预，碳源摄入分别降低15%、30%与45%。本研究采用Affymetrix小鼠基因1.0 ST芯片平台，获取并分析了差异表达基因的转录组数据，共鉴定出446个差异表达基因，并依据其生物学功能进行分类。随着热量限制强度升高，胰岛素/胰岛素样生长因子1（IGF-1）、表皮生长因子（EGF）、转化生长因子β（TGF-β）及经典Wnt信号通路等多条信号通路均呈现逐步下调的趋势；诸多与细胞结构特征相关的基因，如细胞外基质（ECM）、细胞黏附及细胞骨架相关基因，同样随梯度热量限制干预显著下调，且与干预强度呈强相关性。此外，细胞周期与脂肪生成相关基因也出现下调；结合既往研究，上述生物学过程均为前述四条信号通路的调控靶标。与之相反，参与三羧酸循环（TCA）与电子传递链（ETC）等特异性代谢过程的基因则呈现转录水平上调。此外，脂肪组织扩张标志物瘦素（leptin）、中胚层特异性转录本（Mest）及分泌型卷曲相关蛋白5（Sfrp5），以及绝大多数转运与免疫应答相关基因，均因热量限制干预出现下调。本研究通过比较基因表达谱，解析了对18周龄年轻小鼠实施梯度强度（15%、30%、45%）、为期10周的短期热量限制后，其脂肪组织的转录组变化，每组设置3只生物学重复。