Silver nanoparticles inhibit beige fat function and promote adiposity
Silver nanoparticles inhibit beige fat function and promote adiposity
复制标题
纳米银抑制米色脂肪功能，促进肥胖
DOI：
10.1016/j.molmet.2019.01.005
复制
发表时间：
2019
影响因子：
8.1
通讯作者：
Ma Xinran
中科院分区：
文献类型：
--
作者：
Yue Lishu;Zhao Wenjun;Wang Dongmei;Meng Meiyao;Zheng Ying;Li Yu;Qiu Jin;Yu Jian;Yan Yang;Lu Peng;Sun Youmin;Fu Jie;Wang Jiqiu;Zhang Qiang;Xu Lingyan;Ma Xinran
目的肥胖是一种复杂的慢性疾病，在全球范围内高发。多种因素在肥胖的发生中起着不可或缺的作用，人们对现代社会中频繁出现的环境污染物的贡献越来越感兴趣。银纳米颗粒(AgNPs)在日常生活中具有广泛的杀菌作用。然而，其潜在的毒性和在肥胖流行中的作用尚不清楚。方法米色脂肪细胞是新发现的脂肪细胞，其特征是激活时具有高的生热和能量耗散能力，并具有褐变过程。在本研究中，我们在体内评估了AgNPs暴露对米色脂肪细胞分化和功能的影响。我们还系统地研究了AgNPs对小鼠脂肪和代谢性能的影响，以及可能的潜在分子机制。结果表明，AgNPs独立于颗粒大小，抑制米色脂肪细胞的成脂、线粒体和生热基因程序，从而抑制其分化能力、线粒体活性和生热反应。重要的是，暴露在小鼠体内的AgNPs抑制了皮下脂肪中的褐变基因程序，导致能量消耗减少，增加了小鼠的肥胖。从机制上讲，我们发现AgNPs增加了米色脂肪细胞中活性氧化物种(ROS)的水平，并特异性地激活了MAPK-ERK信号。抗氧化剂或ERK抑制剂FR180204可改善AgNPs对米色脂肪细胞的负面影响。结论综合考虑，AgNPs通过抑制米色脂肪细胞的分化和功能，可能通过破坏ROS稳态和ERK磷酸化，在促进肥胖方面发挥了意想不到的作用。今后有必要对AgNPs应用的健康风险及其安全剂量进行评估。
ObjectiveObesity is a complex chronic disease of high prevalence worldwide. Multiple factors play integral roles in obesity development, with rising interest focusing on the contribution of environmental pollutants frequent in modern society. Silver nanoparticles (AgNPs) are widely used for bactericidal purpose in various applications in daily life. However, their potential toxicity and contribution to the obesity epidemic are not clear.MethodsBeige adipocytes are newly discovered adipocytes characterized by high thermogenic and energy dissipating capacity upon activation and the “browning” process. In the present study, we assess the impact of AgNPs exposure on beige adipocytes differentiation and functionality bothin vitroandin vivo. We also systematically investigate the influence of AgNPs on adiposity and metabolic performance in mice, as well as the possible underlying molecular mechanism.ResultsThe results showed that, independent of particle size, AgNPs inhibit the adipogenic, mitochondrial, and thermogenic gene programs of beige adipocytes, thus suppressing their differentiation ability, mitochondrial activity, and thermogenic response. Importantly, exposure to AgNPs in mice suppresses browning gene programs in subcutaneous fat, leading to decreased energy expenditure and increased adiposity in mice. Mechanistically, we found that AgNPs increase reactive oxidative species (ROS) levels and specifically activate MAPK-ERK signaling in beige adipocytes. The negative impacts of AgNPs on beige adipocytes can be ameliorated by antioxidant or ERK inhibitor FR180204 treatment.ConclusionsTaken together, these results revealed an unexpected role of AgNPs in promoting adiposity through the inhibition of beige adipocyte differentiation and functionality, possibly by disrupting ROS homeostasis and ERK phosphorylation. Future assessments on the health risk of AgNPs applications and their safe dosages are warranted.