Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan; Translational Research Center, Research Institute of Science and Technology, Tokyo University of Science, Noda, Japan.
Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
Exp Gerontol. 2018 Apr;104:127-137. doi: 10.1016/j.exger.2018.01.016. Epub 2018 Feb 2.
The beneficial actions of caloric restriction (CR) are partially mediated by metabolic remodeling of white adipose tissue (WAT). Recently, we showed that CR enhances de novo fatty acid (FA) biosynthesis and mitochondrial biogenesis, particularly in WAT. Here, to better understand the response of WAT to CR, we compare the effects of CR on three WAT depots in rats: retroperitoneal (rWAT), epididymal (eWAT) and subcutaneous (sWAT). Computed tomography and histological analysis showed that CR reduced the volume and average size of rWAT adipocytes. In all WAT depots, CR markedly upregulated the expression of proteins involved in FA biosynthesis in fed rats. In visceral WAT (rWAT and eWAT), hormone-sensitive lipase (lipolytic form) phosphorylation was increased by CR under fed conditions, and decreased by CR under fasted conditions. Conversely, in sWAT, hormone-sensitive lipase phosphorylation was increased by CR under fasted conditions. CR enhanced the effect of feeding on AKT activity in sWAT (indicative of a positive effect on insulin sensitivity) but not in rWAT or eWAT. These data suggest that CR improves lipid metabolism in an insulin signaling-dependent manner in sWAT only. The effects of CR on adipokine (adiponectin and leptin) expression were also different among rWAT, eWAT and sWAT, and CR reduced the gene expression of M2 macrophage markers in rWAT and sWAT, but not in eWAT. We conclude that CR differentially affects the characteristics of WAT depots in rats, including adipocyte size, lipid metabolism, insulin signaling, adipocytokine profile and macrophage infiltration.
热量限制（CR）的有益作用部分是通过白色脂肪组织（WAT）的代谢重塑介导的。最近，我们表明 CR 增强了新脂肪酸（FA）的生物合成和线粒体生物发生，特别是在 WAT 中。在这里，为了更好地理解 WAT 对 CR 的反应，我们比较了 CR 对大鼠三种 WAT 隔室的影响：腹膜后（rWAT）、附睾（eWAT）和皮下（sWAT）。计算机断层扫描和组织学分析表明，CR 减少了 rWAT 脂肪细胞的体积和平均大小。在所有 WAT 隔室中，CR 明显上调了进食大鼠中参与 FA 生物合成的蛋白质的表达。在内脏 WAT（rWAT 和 eWAT）中，CR 在进食条件下增加了激素敏感脂肪酶（脂解形式）的磷酸化，而在禁食条件下则减少了 CR 的磷酸化。相反，在 sWAT 中，CR 在禁食条件下增加了激素敏感脂肪酶的磷酸化。CR 增强了 CR 对 sWAT 中 AKT 活性的进食作用（表明对胰岛素敏感性有积极影响），但对 rWAT 或 eWAT 没有影响。这些数据表明，CR 仅以胰岛素信号依赖性方式改善 sWAT 中的脂质代谢。CR 对脂肪因子（脂联素和瘦素）表达的影响在 rWAT、eWAT 和 sWAT 之间也不同，CR 降低了 rWAT 和 sWAT 中 M2 巨噬细胞标志物的基因表达，但在 eWAT 中没有。我们得出结论，CR 以不同的方式影响大鼠 WAT 隔室的特征，包括脂肪细胞大小、脂质代谢、胰岛素信号、脂肪细胞因子谱和巨噬细胞浸润。
