MMP-12 siRNA improves the homeostasis of the small intestine and metabolic dysfunction in high-fat diet feeding-induced obese mice

Biomaterials. 2021 Oct 11;278:121183. doi: 10.1016/j.biomaterials.2021.121183. Online ahead of print.ABSTRACTThe changes of small intestinal homeostasis have been recognized to contribute essentially to the obese development. However, the core small intestinal regulator which mediates over-nutrient impacts on the homeostasis of the small intestines remains elusive. Here, we identify the MMP-12 as such a responsive factor in mouse small intestines. Taking advantages of the nano delivery system, we demonstrate that small intestine-specific MMP-12 knockdown alleviates high-fat diet feeding-induced metabolic disorders and improves intestinal homeostasis in mice, including a significant decrease in lipid transportation, bile acid reabsorption, and inflammation. In parallel, the small intestinal integrity is recovered and the gut microbiota composition is reversed towards that under normal diet feeding. Mechanistically, MMP-12, differing from its traditional elastolytic function, acts as a transcriptional factor to activate Fabp4 transcription through epigenetic modification. In translational medicine, clinical applications of our nanosystem and therapeutic interventions targeting MMP-12 will benefit patients with obesity and associated diseases.PMID:34653936 | DOI:10.1016/j.biomaterials.2021.121183

Source: Biomaterials - October 15, 2021 Category: Materials Science Authors: Mingming Song Shiyao Zhang Zixuan Tao Jianning Li Yujie Shi Yonghong Xiong Wenxiang Zhang Chang Liu Siyu Chen Source Type: research