Theranostics 2020; 10(18):8197-8210. doi:10.7150/thno.43968

Research Paper

Brown adipose tissue-derived exosomes mitigate the metabolic syndrome in high fat diet mice

Xueying Zhou1,2#, Zhelong Li1,2#, Meihao Qi3#, Ping Zhao1, Yunyou Duan1, Guodong Yang2✉, Lijun Yuan1✉

1. Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, People's Republic of China.
2. The State Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, People's Republic of China.
3. Department of Otolaryngology Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China.
#These authors contributed equally to this article.

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Citation:
Zhou X, Li Z, Qi M, Zhao P, Duan Y, Yang G, Yuan L. Brown adipose tissue-derived exosomes mitigate the metabolic syndrome in high fat diet mice. Theranostics 2020; 10(18):8197-8210. doi:10.7150/thno.43968. Available from http://www.thno.org/v10p8197.htm

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Abstract

The ever-increasing incidence of obesity and related disorders impose serious challenges on public health worldwide. Brown adipose tissue (BAT) has strong capacity for promoting energy expenditure and has shown great potential in treating obesity. Exosomes are nanovesicles that share the characteristics of their donor cells. Whether BAT derived exosomes (BAT-Exos) might exert similar metabolic benefits on obesity is worthy of investigation.

Methods: Obese mice were established by high-fat-diet (HFD) feeding and were treated with Seum-Exos or BAT-Exos isolated from young healthy mice. Blood glucose, glucose tolerance and blood lipids were tested in mice with indicated treatments. Histology examinations were performed on adipose tissue, liver and heart by HE staining and/or Oil Red O staining. Echocardiography was performed to evaluate cardiac function of mice. In vivo distribution of exosomes was analyzed by fluorescence labeling and imaging and in vitro effects of exosomes were evaluated by cell metabolism analysis. Protein contents of BAT-Exos were analyzed by mass spectrometry.

Results: The results showed that BAT-Exos reduced the body weight, lowered blood glucose and alleviated lipid accumulation in HFD mice independently of food intake. Echocardiography revealed that the abnormal cardiac functions of HFD mice were significantly restored after treatment with BAT-Exos. Cell metabolism analysis showed that treatment with BAT-Exos significantly promoted oxygen consumption in recipient cells. Protein profiling of exosomes demonstrated that BAT-Exos were rich in mitochondria components and involved in catalytic processes.

Conclusions: Collectively, our study showed that BAT-Exos significantly mitigated the metabolic syndrome in HFD mice. Detailed elucidation of the reactive molecules and mechanism of action would provide new insights in combating obesity and related disorders.

Keywords: Exosomes, brown adipose tissue, obesity, cell-free therapy, cardiovascular diseases