期刊
BIOMATERIALS
卷 276, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.121030
关键词
Metabolic dysfunction-associated fatty liver disease; Hydrogen medicine; Liver metabolism; Hydrogen delivery
资金
- Instrumental Analysis Center of Shenzhen University (Lihu campus)
- National Natural Science Foundation of China [51872188, 81870605, 81800383, 81770855]
- Guangdong Provincial Science and Technology Program [2019B030301009]
- Shenzhen Basic Research Program [JCYJ20170818093808351, JCYJ20190808170401660, JCYJ2019080817040]
- Shenzhen Key Laboratory of Metabolism and Cardiovascular Homeostasis [ZDSYS20190902092903237]
- Special Funds for the Development of Strategic Emerging Industries in Shenzhen [20180309154519685]
- SZU Top Ranking Project [860-00000210]
- Taishan Scholars from the Shandong Province Government [ts201511057]
- Academic Promotion Programme of Shandong First Medical University [2019ql010, 2019pt009]
- Center of Hydrogen Science, Shanghai Jiao Tong University, China
The hydrogen nanocapsule encapsulating hydrogen gas can effectively treat early-stage MAFLD, obesity, and diabetes by promoting gut microbiota balance and reprogramming liver metabolism.
Metabolic dysfunction-associated fatty liver disease (MAFLD) is estimated to affect a quarter of all population and represents a major health threat to all societies. Yet, currently no approved pharmacological treatment is available for MAFLD. H-2-rich water has recently been reported to reduce hepatic lipid accumulation in MAFLD patients but its efficacy is limited due to low H-2 dosage. Increasing H-2 dose may enhance its therapeutic effects but remains technically challenging. In this study, we designed and synthesized a hydrogen nanocapsule by encapsulating ammonia borane into hollow mesoporous silica nanoparticles to achieve ultrahigh and sustained H-2 release in the gut. We then investigated its efficacy in treating early-stage MAFLD and other metabolic dysfunctions such as obesity and diabetes. The hydrogen nanocapsule attenuated both diet-induced and genetic mutation induced early-stage MAFLD, obesity, and diabetes in mice, without any tissue toxicity. Mechanistically, we discovered that sustained and ultrahigh H-2 supply by hydrogen nanocapsule increased, among other species, the abundance of Akkermansia muciniphila, highlighting reshaped gut microbiota as a potential mechanism of H-2 in treating metabolic dysfunctions. Moreover, hepatic transcriptome showed a reprogramed liver metabolism profile with reduced lipid synthesis and increased fatty acid metabolism.
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