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

Molecular Metabolism (Apr 2019)

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

Affiliations

Lishu Yue: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China
Wenjun Zhao: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China
Dongmei Wang: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China
Meiyao Meng: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China
Ying Zheng: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China
Yu Li: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China
Jin Qiu: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China
Jian Yu: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China
Yang Yan: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China
Peng Lu: Department of Endocrinology and Metabolism, China National Research Center for Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
Youmin Sun: Department of Environmental Science & Engineering, Fudan University, Shanghai, 200433, China
Jie Fu: Department of Environmental Science & Engineering, Fudan University, Shanghai, 200433, China
Jiqiu Wang: Department of Endocrinology and Metabolism, China National Research Center for Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
Qiang Zhang: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China
Lingyan Xu: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China; Corresponding author.
Xinran Ma: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China; Corresponding author.

Journal volume & issue: Vol. 22
pp. 1 – 11

Abstract

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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. Keywords: Adiposity, Beige fat, Silver nanoparticles, Browning, Energy expenditure, Reactive oxidative species

Published in Molecular Metabolism

ISSN: 2212-8778 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine
Website: https://www.journals.elsevier.com/molecular-metabolism/

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