Silver nanoparticles inhibit beige fat function and promote adiposity

Lishu Yue, Wenjun Zhao, Dongmei Wang, Meiyao Meng, Ying Zheng, Yu Li, Jin Qiu, Jian Yu, Yang Yan, Peng Lu, Youmin Sun, Jie Fu, Jiqiu Wang, Qiang Zhang, Lingyan Xu, Xinran Ma

Nanoparticles, ultrafine particles of 1 to 100 nm in size, show unique optical, electrical, or thermal properties. The recent decade has seen an exponential growth in the fabrication of nanoparticles, commonly termed as engineered nanoparticles (ENPs). Silver nanoparticles (AgNPs) are among the most widely used ENPs. However, concerns have been raised about their safety and potential influence on human health. The potential contribution of AgNPs specifically to obesity as well as the underlying mechanism have not yet been addressed. Yue, Zhao, Wang, et al. studied the in vitro effects of AgNPs on beige adipocyte differentiation and function, as well as their in vivo influence on beige fat and metabolic parameters of mice on a high fat diet. Their results show that AgNPs suppress beige adipocyte development and function. This suggests that environmental exposure with AgNPs may contribute to the obesity epidemic.

Objective: Obesity 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.

Methods: Beige 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 both in vitro and in vivo. We also systematically investigate the influence of AgNPs on adiposity and metabolic performance in mice, as well as the possible underlying molecular mechanism.

Results: The 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.

Conclusions: Taken 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.