Sleeve Gastroplasty Combined with the NLRP3 Inflammasome Inhibitor CY-09 Reduces Body Weight, Improves Insulin Resistanc
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ORIGINAL CONTRIBUTIONS
Sleeve Gastroplasty Combined with the NLRP3 Inflammasome Inhibitor CY-09 Reduces Body Weight, Improves Insulin Resistance and Alleviates Hepatic Steatosis in Mouse Model Kangyue Sun 1 & Jing Wang 1 & Zhixian Lan 1 & Ling Li 2 & Yadong Wang 1 & Aimin Li 1 & Side Liu 1 & Yue Li 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose Endoscopic sleeve gastroplasty (ESG) has been suggested to be effective for treating obesity and its related nonalcoholic 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. Material and Methods Forty mice were randomly divided into a control group (n = 5) and an NAFLD group (n = 35) fed by highfat 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). Results 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−2, P = 0.036) and NAS (4.5 ± 1.3 vs. 8.0 ± 1.8, P = 0.006) were also observed in the combination group. Conclusions 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. Keywords Endoscopic sleeve gastroplasty . NAFLD . NLRP3 inflammasome . CY-09
Introduction Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases; 20% of cases progress to non-alcoholic steatohepatitis (NASH), and NAFLD is estimated to be the leading cause of end-stage liver disease [1, 2].
Kangyue Sun and Jing Wang contributed equally to this work. * Side Liu [email protected] * Yue Li [email protected] 1
Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
2
Division of Gastroenterology and Hepatology, The Johns Hopkins School of Medicine, Baltimore, MD, USA
Bariatric operations have demonstrated beneficial effects on NAFLD, inducing histological resolution of liver damage through weight loss-dependent and weight loss-independent mechanisms [3, 4]. Endoscopic sleeve gastroplasty (ESG) and vertical sleeve gastrectomy (VSG), despite being methodologically different, can reduce gastric volume and improvements in the metabol
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