Institute of Biological and Environmental Sciences, University of Aberdeen, UK.
Centre for Genome Enabled Biology and Medicine, University of Aberdeen, UK.
J Gerontol A Biol Sci Med Sci. 2018 Mar 2;73(3):279-288. doi: 10.1093/gerona/glx101.
Calorie restriction (CR) leads to a remarkable decrease in adipose tissue mass and increases longevity in many taxa. Since the discovery of leptin, the secretory abilities of adipose tissue have gained prominence in the responses to CR. We quantified transcripts of epididymal white adipose tissue of male C57BL/6 mice exposed to graded levels of CR (0-40% CR) for 3 months. The numbers of differentially expressed genes (DEGs) involved in NF-κB, HIF1-α, and p53 signaling increased with increasing levels of CR. These pathways were all significantly downregulated at 40% CR relative to 12 h ad libitum feeding. In addition, graded CR had a substantial impact on DEGs associated with pathways involved in angiogenesis. Of the 497 genes differentially expressed with graded CR, 155 of these genes included a signal peptide motif. These putative signaling proteins were involved in the response to ketones, TGF-β signaling, negative regulation of insulin secretion, and inflammation. This accords with the previously established effects of graded CR on glucose homeostasis in the same mice. Overall these data suggest reduced levels of adipose tissue under CR may contribute to the protective impact of CR in multiple ways linked to changes in a large population of secreted proteins.
热量限制（CR）可显著减少脂肪组织质量，并延长许多分类群的寿命。自瘦素发现以来，脂肪组织的分泌能力在 CR 反应中受到了关注。我们定量分析了雄性 C57BL/6 小鼠暴露于不同程度 CR（0-40% CR）3 个月后附睾白色脂肪组织的转录本。参与 NF-κB、HIF1-α 和 p53 信号通路的差异表达基因（DEGs）数量随着 CR 水平的增加而增加。与 12 小时随意进食相比，这些通路在 40% CR 时均显著下调。此外，分级 CR 对与血管生成途径相关的 DEGs 有显著影响。在 497 个与分级 CR 差异表达的基因中，有 155 个基因包含信号肽基序。这些推测的信号蛋白参与了对酮体、TGF-β 信号、胰岛素分泌的负调控以及炎症的反应。这与之前在相同小鼠中建立的分级 CR 对葡萄糖稳态的影响一致。总的来说，这些数据表明，在 CR 下脂肪组织水平降低可能以多种方式有助于 CR 的保护作用，这些方式与大量分泌蛋白的变化有关。
