Kamohara Ryotaro, Yamaza Haruyoshi, Tsuchiya Tomoshi, Komatsu Toshimitsu, Park Seongjoon, Hayashi Hiroko, Chiba Takuya, Mori Ryoichi, Otabe Shuichi, Yamada Kentaro, Nagayasu Takeshi, Shimokawa Isao
Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, 852-8523, Japan; Department of Surgical Oncology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, 852-8501, Japan.
Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, 852-8523, Japan.
Exp Gerontol. 2015 Apr;64:46-54. doi: 10.1016/j.exger.2015.02.011. Epub 2015 Feb 16.
Adiponectin (Adipoq), a peptide hormone secreted from the white adipose tissue, may play a role in the anti-aging and/or anti-tumor effects of calorie restriction (CR). We analyzed metabolic traits in Adipoq gene-overexpressing mice fed ad libitum with a regular diet (RD) or a high-fat diet (HFD), or fed 30% CR of RD initiated at 12 weeks of age. Adipoq-RD and -HFD mice at 6 months of age showed reduced blood glucose and insulin concentrations, and thus increased insulin sensitivity, compared with WT mice fed a RD or a HFD. In the epididymal white adipose tissue in Adipoq mice, senescence-like changes such as upregulation of p53 protein and of biomarkers of inflammation, Cd68 and Ccl2 mRNA, were ameliorated compared with WT-RD and WT-HFD mouse tissues. Resistance to stress induced by lipopolysaccharide was also strengthened in Adipoq mice compared with WT mice. These metabolic changes and stress resistance were also noted in the WT-CR mice, suggesting that Adipoq plays a part in the effect of CR. In contrast, in an allograft tumor growth model, tumor growth was not inhibited in Adipoq mice. The present findings suggest that Adipoq plays a part in the anti-aging, but not in the anti-tumor, effects of CR.
脂联素（Adipoq）是一种由白色脂肪组织分泌的肽类激素，可能在热量限制（CR）的抗衰老和/或抗肿瘤作用中发挥作用。我们分析了自由采食常规饮食（RD）或高脂饮食（HFD），或在12周龄开始给予30%RD热量限制的脂联素基因过表达小鼠的代谢特征。与喂食RD或HFD的野生型（WT）小鼠相比，6月龄的脂联素-RD和 -HFD小鼠血糖和胰岛素浓度降低，胰岛素敏感性增加。在脂联素小鼠的附睾白色脂肪组织中，与WT-RD和WT-HFD小鼠组织相比，p53蛋白以及炎症生物标志物Cd68和Ccl2 mRNA上调等衰老样变化得到改善。与WT小鼠相比，脂联素小鼠对脂多糖诱导的应激的抵抗力也增强。在WT-CR小鼠中也观察到了这些代谢变化和应激抵抗力，表明脂联素在CR的作用中发挥了作用。相比之下，在同种异体肿瘤生长模型中，脂联素小鼠的肿瘤生长没有受到抑制。目前的研究结果表明，脂联素在CR的抗衰老作用中发挥作用，但在抗肿瘤作用中不发挥作用。
