NLRP3 inflammasome inhibitor CY-09 reduces hepatic steatosis in experimental NAFLD mice
| Autor: | Yuqiang Nie, Side Liu, Kangyue Sun, Yongjian Zhou, Xianfei Wang, Yue Li, Hong Wang, Youlian Zhou |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Biophysics Carbohydrate metabolism Diet High-Fat Biochemistry Gastroenterology Pathogenesis 03 medical and health sciences 0302 clinical medicine Insulin resistance Non-alcoholic Fatty Liver Disease Internal medicine medicine Animals Molecular Biology Triglycerides business.industry Body Weight Fatty liver Area under the curve Thiones nutritional and metabolic diseases Inflammasome Cell Biology medicine.disease Mice Inbred C57BL Disease Models Animal 030104 developmental biology 030220 oncology & carcinogenesis Thiazolidines Insulin Resistance Steatosis business Homeostasis medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 534:734-739 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2020.11.009 |
| Popis: | Aims Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases. The NOD-like receptor protein 3 (NLRP3) inflammasome was suggested to be involved in the pathogenesis of NAFLD. A small-molecule named CY-09 is a new selective and direct inhibitor of the NLRP3 inflammasome. We aimed to investigate whether CY-09 is effective for the treatment of NAFLD in a high-fat diet (HFD)-induced mouse model. Methods Twenty mice were fed by HFD for 14 weeks, and then were randomly assigned into two groups: (1) control group receiving dimethylsulfoxide (DMSO) solution; (2) CY-09 group receiving CY-09 injection. In an 8-week follow-up, oral glucose tolerance test (OGTT) and homeostasis model assessment of insulin resistance (HOMA-IR) were used to measure glucose metabolism. Liver steatosis was evaluated by the NAFLD activity score (NAS) and deemed as the primary outcome. Results The body weight in CY-09 group was significantly lower than the DMSO control group on 27 weeks (41.0 ± 3.5 g vs. 49.7 ± 5.2 g, P = 0.014). The area under the curve (AUC) of OGTT was less in CY-09 group than that in DMSO group (35.81 ± 6.79 vs. 22.91 ± 2.58 mmol/L·hr, P = 0.004), as well as HOMA-IR (14.36 ± 3.89 vs. 8.82 ± 2.04 mmol.mIU.L-2, P = 0.023). Microscopically, liver lipid droplets dramatically improved and significantly lower NAS was observed in CY-09 group (8.25 ± 1.26 vs. 3.20 ± 0.45, P Conclusion CY-09 reduces hepatic steatosis in experimental NAFLD mice and CY-09 may be a potential therapeutic drug of NAFLD in clinical practice. |
| Databáze: | OpenAIRE |
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