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Sleeve Gastroplasty Combined with the NLRP3 Inflammasome Inhibitor CY-09 Reduces Body Weight, Improves Insulin Resistance and Alleviates Hepatic Steatosis in Mouse Model

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Abstract

Purpose

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.

Material and Methods

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).

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.

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Data Availability

All the data supporting the results will be available and stored at the research office of our department.

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Authors’ Contribution Statement

Side Liu and Yue Li designed the study. Yue Li drafted the manuscript. Kangyue Sun and Jing Wang conducted the experiment and recorded the data. Kangyue Sun and Zhixian Lan analysed the experimental data. Ling Li and Aimin Li revised the manuscript. Yadong Wang reviewed and evaluated the hepatic histology.

Funding

The study was supported by the National Natural Science Foundation of China (No. 81600460), the Natural Science Foundation of Guangdong Province (No. 2016A030310382) and the Guangdong Gastrointestinal Disease Research Center (No. 2017B020209003). All authors disclosed no financial relationships relevant to this publication.

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Author notes

  1. Kangyue Sun and Jing Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China

    Kangyue Sun, Jing Wang, Zhixian Lan, Yadong Wang, Aimin Li, Side Liu & Yue Li

  2. Division of Gastroenterology and Hepatology, The Johns Hopkins School of Medicine, Baltimore, MD, USA

    Ling Li

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  1. Kangyue Sun
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Correspondence to Side Liu or Yue Li.

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The authors declare that they have no conflict of interest.

Ethical Approval Statement

The authors declare that an ethical approval was obtained for our study. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted and ethical approval was obtained from the Southern Medical University for the Ethical Use and Care of Experimental Animals. All applicable institutional and/or national guidelines for the care and use of animals were followed.

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Sun, K., Wang, J., Lan, Z. et al. Sleeve Gastroplasty Combined with the NLRP3 Inflammasome Inhibitor CY-09 Reduces Body Weight, Improves Insulin Resistance and Alleviates Hepatic Steatosis in Mouse Model. OBES SURG 30, 3435–3443 (2020). https://doi.org/10.1007/s11695-020-04571-8

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  • DOI: https://doi.org/10.1007/s11695-020-04571-8

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