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腹腔镜胃折叠术后肥胖患者血清蛋白质组变化和脂肪量的加速减少。

Serum proteome changes and accelerated reduction of fat mass after laparoscopic gastric plication in morbidly obese patients.

机构信息

Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran; Department of Health Science and Technology, Aalborg University, Denmark.

Department of Health Science and Technology, Aalborg University, Denmark.

出版信息

J Proteomics. 2019 Jul 15;203:103373. doi: 10.1016/j.jprot.2019.05.001. Epub 2019 May 3.

DOI:10.1016/j.jprot.2019.05.001
PMID:31054967
Abstract

Laparoscopic Gastric Plication (LGP) is a relatively new bariatric surgical procedure which no part of the stomach is removed. It is not clearly understood how LGP leads to fatty tissue reduction. We aimed to investigate the impact of LGP on serum proteome and understand molecular mechanisms of LGP-induced weight loss post-surgery. A Prospective observational study of 16 obese individuals who underwent LGP was performed. A Label-free quantitative shotgun proteomics approach was used to compare serum proteome of subjects before surgery with serum of the same individuals 1 to 2 months post-surgery (T1) and 4 to 5 months post-surgery (T2). The proteome analysis revealed that 48 proteins were differentially regulated between pre-surgery and T1, and seven proteins between pre-surgery and T2 of which six proteins were shared between the two timepoints. Among differentially regulated proteins, four proteins (SRGN, FETUB, LCP1 and CFP) have not previously been described in the context of BMI/weight loss. Despite few differences following LGP, most regulated serum proteins are in accordance with alternative weight loss procedures. Pathway analysis revealed changes to lipid- and inflammatory pathways, including PPARα/RXRα, LXR/RXR and FXR/RXR activation, especially at T1. At T2, the pathways related to inflammation and immune system are most affected. SIGNIFICANCE: Among the available clinical therapies for morbid obesity, bariatric surgery is considered as the most effective approach to achieve long-term weight loss, alongside a significant improvement in metabolic syndrome. However, very little is known about the underlying mechanism associated with significant weight loss post-surgery. Understanding such mechanisms could lead to development of safer non-surgical weight loss approaches. We here present the first analysis of the impact of LGP on the serum proteome, to bring new insights into the underlying molecular mechanism. Our findings indicate that LGP has a comprehensive systemic effect based on the blood serum proteome profile which might account for accelerated reduction of fat mass after surgery, thus, food restriction is not the only reason for weight loss following this unique surgical approach. As secretory regions of the stomach are preserved in LGP and it is associated with minimal physiological and anatomical changes, the findings are of high importance in the field of bariatric surgery and weight loss.

摘要

腹腔镜胃折叠术(LGP)是一种相对较新的减肥手术,不会切除胃的任何部分。目前还不清楚 LGP 如何导致脂肪组织减少。我们旨在研究 LGP 对血清蛋白质组的影响,并了解手术后 LGP 诱导体重减轻的分子机制。对 16 名接受 LGP 的肥胖个体进行了前瞻性观察研究。使用无标记定量 shotgun 蛋白质组学方法比较了手术前患者的血清蛋白质组与手术后 1 至 2 个月(T1)和 4 至 5 个月(T2)的相同个体的血清蛋白质组。蛋白质组分析显示,术前与 T1 之间有 48 种蛋白质差异调节,术前与 T2 之间有 7 种蛋白质差异调节,其中 6 种蛋白质在两个时间点之间共享。在差异调节的蛋白质中,有 4 种蛋白质(SRGN、FETUB、LCP1 和 CFP)在 BMI/体重减轻的背景下尚未被描述过。尽管 LGP 后差异很小,但大多数调节的血清蛋白质与其他减肥方法一致。途径分析显示脂质和炎症途径发生变化,包括 PPARα/RXRα、LXR/RXR 和 FXR/RXR 激活,尤其是在 T1。在 T2 时,受影响最大的是与炎症和免疫系统相关的途径。意义:在肥胖症的现有临床治疗方法中,减肥手术被认为是实现长期减肥和代谢综合征显著改善的最有效方法。然而,对于与手术后显著体重减轻相关的潜在机制知之甚少。了解这些机制可能会导致开发更安全的非手术减肥方法。我们在这里首次分析了 LGP 对血清蛋白质组的影响,为潜在的分子机制提供了新的见解。我们的研究结果表明,LGP 对基于血清蛋白质组谱的全身系统具有全面的影响,这可能是手术后脂肪量加速减少的原因,因此,手术后体重减轻不仅仅是饮食限制的原因。由于 LGP 保留了胃的分泌区域,并且与最小的生理和解剖变化相关,因此这些发现对于减肥手术和减肥领域非常重要。

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