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Introduction <p>Obesity and related metabolic diseases are major global health challenges. Metabolic and bariatric surgery (MBS) is an effective treatment. Yet exploring its molecular mechanisms remains limite due to the challenge of obtaining postoperative tissue samples. While rat models are more convenient in size and operation, mouse models offer unique advantages such as lower breeding costs and easier genetic modification. However, research on mouse MBS models is still limited because of their small size and surgical complexity, highlighting the need for optimized techniques to advance the field.</p> Objective <p>This study aims to establish a high-fat diet-induced (HFD) obesity combined with metabolic dysfunction-associated steatotic liver disease (MASLD) mouse model, and to evaluate the MBS models assisted by microsurgery, so as to provide a reliable tool for mechanism research.</p> Methods <p>Male SPF C57BL/6J mice were randomly assigned to the normal diet (ND) group and the HFD group. The mouse in the HFD group were induced to develop obesity with MASLD through a high-fat diet for 16 weeks. The HFD group was further divided into sham operation group (Sham), sleeve gastrectomy (SG) group, and modified Roux-en-Y gastric bypass (RYGB) group (<i>n</i> = 6). Metabolic efficacy was evaluated by weight, metabolic parameters, and pathological staining analysis at the 4th week post-surgery.</p> Results <p>Compared with the ND group, the weight of the HFD group increased by 38.25% (<i>P</i> &lt; 0.001), and the liver tissue showed pathological features of MASLD. Compared with the Sham group, the weight of the SG group and the modified RYGB group decreased significantly at 4 weeks after operation (<i>P</i> &lt; 0.05). Compared with the Sham group, the insulin sensitivity of the RYGB group was improved. Hepatic steatosis was significantly reduced in SG and RYGB groups, and serum TG and LDL levels were significantly improved. The postoperative survival rate of SG and Sham mice was 100%, and RYGB was 83.3% (1 case died of anastomotic stenosis).</p> Conclusion <p>The establishment of a modified RYGB and SG mouse model has good reproducibility, safety, and efficacy. This study provides a useful tool for exploring the mechanism of MBS in the treatment of obesity with MASLD.</p>

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Construction and metabolic efficacy evaluation of sleeve gastrectomy and modified Roux-en-Y gastric bypass in a mouse model with obesity and MASLD

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月20日

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  • Zheng Wang,
  • Zhehong Li,
  • Chenxu Tian,
  • Chengyuan Yu,
  • Xiyuan Chen,
  • Yilan Sun,
  • Weijian Chen,
  • Dezhong Wang,
  • Liang Wang,
  • Dongbo Lian,
  • Nengwei Zhang

摘要

Introduction

Obesity and related metabolic diseases are major global health challenges. Metabolic and bariatric surgery (MBS) is an effective treatment. Yet exploring its molecular mechanisms remains limite due to the challenge of obtaining postoperative tissue samples. While rat models are more convenient in size and operation, mouse models offer unique advantages such as lower breeding costs and easier genetic modification. However, research on mouse MBS models is still limited because of their small size and surgical complexity, highlighting the need for optimized techniques to advance the field.

Objective

This study aims to establish a high-fat diet-induced (HFD) obesity combined with metabolic dysfunction-associated steatotic liver disease (MASLD) mouse model, and to evaluate the MBS models assisted by microsurgery, so as to provide a reliable tool for mechanism research.

Methods

Male SPF C57BL/6J mice were randomly assigned to the normal diet (ND) group and the HFD group. The mouse in the HFD group were induced to develop obesity with MASLD through a high-fat diet for 16 weeks. The HFD group was further divided into sham operation group (Sham), sleeve gastrectomy (SG) group, and modified Roux-en-Y gastric bypass (RYGB) group (n = 6). Metabolic efficacy was evaluated by weight, metabolic parameters, and pathological staining analysis at the 4th week post-surgery.

Results

Compared with the ND group, the weight of the HFD group increased by 38.25% (P < 0.001), and the liver tissue showed pathological features of MASLD. Compared with the Sham group, the weight of the SG group and the modified RYGB group decreased significantly at 4 weeks after operation (P < 0.05). Compared with the Sham group, the insulin sensitivity of the RYGB group was improved. Hepatic steatosis was significantly reduced in SG and RYGB groups, and serum TG and LDL levels were significantly improved. The postoperative survival rate of SG and Sham mice was 100%, and RYGB was 83.3% (1 case died of anastomotic stenosis).

Conclusion

The establishment of a modified RYGB and SG mouse model has good reproducibility, safety, and efficacy. This study provides a useful tool for exploring the mechanism of MBS in the treatment of obesity with MASLD.