Sun Kangyue, Wang Jing, Lan Zhixian, Li Ling, Wang Yadong, Li Aimin, Liu Side, Li Yue
Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Division of Gastroenterology and Hepatology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
Obes Surg. 2020 Sep;30(9):3435-3443. doi: 10.1007/s11695-020-04571-8.
Endoscopic sleeve gastroplasty (ESG) has been suggested to be effective for treating obesity and its related non-alcoholic fatty liver disease (NAFLD). A small molecule named CY-09 is the selective inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome. We aim to investigate whether a surgery imitating ESG combined with CY-09 is more effective for treatment of obesity and NAFLD in a mouse model.
Forty mice were randomly divided into a control group (n = 5) and an NAFLD group (n = 35) fed by high-fat diet (HFD). The NAFLD mice were randomly assigned to the following groups at the timepoint of 19 weeks: (1) sham surgery; (2) surgery; (3) the combination of surgery with CY-09 injection. NAFLD activity score (NAS) was used for histological evaluation of steatosis. We also detected fasting glucose and insulin to measure the homeostasis model assessment of insulin resistance (HOMA-IR).
HFD resulted in significant obesity and metabolic disorders, indicating successful modelling of obesity and NAFLD. The combination therapy resulted in significantly lower body weight than surgery alone at the end of the 8-week follow-up (40.4 ± 4.8 vs. 45.0 ± 2.2 g, P = 0.025). Furthermore, more dramatic improvements in HOMA-IR (5.8 ± 1.1 vs. 12.2 ± 2.1 mmol mIU L, P = 0.036) and NAS (4.5 ± 1.3 vs. 8.0 ± 1.8, P = 0.006) were also observed in the combination group.
Surgery imitating ESG combined with CY-09 reduces body weight, improves insulin resistance and alleviates hepatic steatosis. The combination therapy may be a promising method for treating obesity and NAFLD.
内镜下袖状胃成形术（ESG）已被证明对治疗肥胖症及其相关的非酒精性脂肪性肝病（NAFLD）有效。一种名为CY-09的小分子是含核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）炎性小体的选择性抑制剂。我们旨在研究在小鼠模型中，模仿ESG的手术联合CY-09是否对肥胖症和NAFLD的治疗更有效。
40只小鼠随机分为对照组（n = 5）和高脂饮食（HFD）喂养的NAFLD组（n = 35）。在19周时，将NAFLD小鼠随机分为以下几组：（1）假手术组；（2）手术组；（3）手术联合CY-09注射组。采用NAFLD活动评分（NAS）对肝脂肪变性进行组织学评估。我们还检测了空腹血糖和胰岛素，以测量胰岛素抵抗的稳态模型评估（HOMA-IR）。
高脂饮食导致显著的肥胖和代谢紊乱，表明肥胖症和NAFLD建模成功。在8周随访结束时，联合治疗组的体重显著低于单纯手术组（40.4±4.8 vs. 45.0±2.2 g，P = 0.025）。此外，联合治疗组的HOMA-IR（5.8±1.1 vs. 12.2±2.1 mmol mIU L，P = 0.036）和NAS（4.5±1.3 vs. 8.0±1.8，P = 0.006）也有更显著的改善。
模仿ESG的手术联合CY-09可减轻体重、改善胰岛素抵抗并减轻肝脏脂肪变性。联合治疗可能是治疗肥胖症和NAFLD的一种有前景的方法。
