Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, China.
Nutrients. 2022 Jul 7;14(14):2796. doi: 10.3390/nu14142796.
Brown adipose tissue (BAT) is of great importance in rodents for maintaining their core temperature via non-shivering thermogenesis in the mitochondria. BAT's thermogenic function has been shown to decline with age. The activation of adenosine 5'-monophosphate (AMP)-activated protein kinase/sirtuin-1 (AMPK/Sirt-1) is effective in regulating mitochondrial function. Exogenous nucleotides (NTs) are regulatory factors in many biological processes. Nicotinamide mononucleotide (NMN), which is a derivative of NTs, is widely known as a Sirt-1 activator in liver and muscle, but the effect of NMN and NTs on aging BAT has not been studied before. The purpose of this study was to investigate the effect of NTs on aging senescence-accelerated mouse prone-8 (SAMP8) mice. Senescence-accelerated mouse resistant 1 (SAMR1) mice were set as the model control group and NMN was used as the positive control. Male, 3 month old SAMP8 mice were divided into the SAMP8-normal chow (SAMP8-NC), SAMP8-young-normal chow (SAMP8-young-NC), NMN, NTs-free, NTs-low, NTs-medium, and NTs-high groups for long-term feeding. After 9 months of intervention, interscapular BAT was collected for experiments. Compared to the SAMP8-NC, the body weight and BAT mass were significantly improved in the NT-treated aging SAMP8 mice. NT supplementation had effects on oxidative stress in BAT. The concentration of malondialdehyde (MDA) was reduced and that of superoxide dismutase (SOD) increased significantly. Meanwhile, the expression of the brown adipocyte markers uncoupling protein-1 (UCP-1), peroxisome proliferator-activated receptor-γ coactlvator-1α (PGC-1α), and PR domain zinc finger protein 16 (PRDM16) were upregulated. The upregulated proteins may be activated via the Sirt-1 pathway. Thus, NT supplementation may be helpful to improve the thermogenesis of BAT by reducing oxidative stress and activating the Sirt-1 pathway.
棕色脂肪组织（BAT）在维持啮齿动物核心体温方面具有重要意义，通过线粒体中的非颤抖产热来实现。已经证明，BAT 的产热功能会随着年龄的增长而下降。激活腺苷 5'-单磷酸（AMP）激活的蛋白激酶/沉默调节蛋白 1（AMPK/Sirt-1）可有效调节线粒体功能。外源性核苷酸（NTs）是许多生物过程的调节因子。烟酰胺单核苷酸（NMN）是 NTs 的衍生物，作为肝脏和肌肉中的 Sirt-1 激活剂广为人知，但 NMN 和 NTs 对衰老 BAT 的影响尚未研究过。本研究旨在探讨 NTs 对衰老加速型小鼠易感 8 号（SAMP8）小鼠的影响。将加速衰老型小鼠抵抗 1 号（SAMR1）小鼠设为模型对照组，并使用 NMN 作为阳性对照。雄性，3 月龄 SAMP8 小鼠分为 SAMP8-正常饲料（SAMP8-NC）、SAMP8-年轻正常饲料（SAMP8-young-NC）、NMN、NT 无、NT 低、NT 中、NT 高组进行长期喂养。干预 9 个月后，收集肩胛间 BAT 进行实验。与 SAMP8-NC 相比，NT 处理的衰老 SAMP8 小鼠的体重和 BAT 质量显著改善。NT 补充对 BAT 的氧化应激有影响。丙二醛（MDA）浓度显著降低，超氧化物歧化酶（SOD）浓度显著升高。同时，褐色脂肪细胞标志物解偶联蛋白 1（UCP-1）、过氧化物酶体增殖物激活受体-γ 共激活物-1α（PGC-1α）和 PR 结构域锌指蛋白 16（PRDM16）的表达上调。上调的蛋白可能通过 Sirt-1 途径被激活。因此，NT 补充可能有助于通过降低氧化应激和激活 Sirt-1 途径来改善 BAT 的产热。
