Gastric dilation following vertical sleeve gastrectomy reflects adaptive stem cell-driven regeneration without association with weight regain or increased cancer risk

IF 5.1 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-08-13 DOI:10.1016/j.lfs.2025.123899

Oluwatosin Asunloye , Ruchita Shelat , McKenzie McCarthy , Britney Le , Rima Patel , Amit Elad , Haya Benhayon , Rachel Ben-Haroush Schyr , Danny Ben-Zvi , Ki-Suk Kim

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引用次数: 0

Abstract

Aims

Bariatric surgery is the most effective intervention for sustained weight loss and the improvement of obesity-related comorbidities. Among these procedures, vertical sleeve gastrectomy (VSG) is the most commonly performed worldwide. Yet, post-VSG gastric dilation has been hypothesized to contribute to failure in weight loss or even weight regain by increasing the secretion of ghrelin, an orexigenic hormone primarily produced in the stomach. However, the relationship between gastric dilation, its underlying mechanism, and its clinical implications remain unclear.

Materials and methods

To investigate this, we utilized both a mouse model of VSG and corpus epithelial samples from patients who had undergone VSG.

Key findings

Using a diet-induced obese mouse model, we found that VSG leads to significant gastric remodeling, yet neither stomach expansion nor increased ghrelin secretion correlated with weight regain. Single-cell RNA sequencing of corpus epithelial cells from VSG patients further revealed an associated with epithelial regeneration, marked by gastric stem cell expansion and upregulation of repair-associated genes. RNA sequencing also showed enhanced stem cell activity alongside upregulation of tumor suppressor genes and long non-coding RNAs, suggesting a potential protective mechanism against gastric cancer despite rapid cellular proliferation.

Significance

These findings challenge the assumption that gastric dilation is a predictor of poor surgical outcomes and instead suggest that it is an adaptive response to VSG, offering new insights into post-VSG gastric remodeling.

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垂直袖胃切除术后胃扩张反映了适应性干细胞驱动的再生，与体重恢复或癌症风险增加无关。

目的：减肥手术是持续减肥和改善肥胖相关合并症的最有效干预措施。在这些手术中，垂直套管胃切除术（VSG）是世界范围内最常用的手术。然而，vsg后胃扩张被假设为通过增加胃促生长素（一种主要在胃中产生的促氧激素）的分泌而导致减肥失败甚至体重反弹。然而，胃扩张及其潜在机制与临床意义之间的关系尚不清楚。材料和方法：为了研究这一点，我们使用了VSG小鼠模型和VSG患者的体上皮样本。主要发现：通过饮食诱导的肥胖小鼠模型，我们发现VSG导致显著的胃重塑，但胃扩张和胃饥饿素分泌增加与体重恢复无关。VSG患者体上皮细胞的单细胞RNA测序进一步揭示了与上皮再生相关的基因，其特征是胃干细胞扩增和修复相关基因上调。RNA测序还显示，干细胞活性增强，肿瘤抑制基因和长链非编码RNA上调，提示尽管细胞快速增殖，但对胃癌有潜在的保护机制。意义：这些发现挑战了胃扩张是不良手术结果的预测因子的假设，相反表明胃扩张是对VSG的适应性反应，为VSG后胃重塑提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.