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胃旁路手术影响肥胖女性肠道叶酸代谢途径相关基因的表达。

Roux-en-Y gastric bypass affects the expression of genes related to the intestinal folate metabolism pathway in obese women.

机构信息

Laboratory of Nutrition and Metabolic Surgery of the Digestive Tract, Department of Gastroenterology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

Laboratory of Nutrition and Metabolic Surgery of the Digestive Tract, Department of Gastroenterology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

出版信息

Nutrition. 2023 Aug;112:112054. doi: 10.1016/j.nut.2023.112054. Epub 2023 Apr 16.

Abstract

OBJECTIVES

Roux-en-Y gastric bypass (RYGB) promotes sustained weight loss, and the resulting new gastrointestinal anatomy can contribute to nutritional depletions. Folate deficiency is one of the most frequently observed nutritional deficiencies after RYGB. The aim of this study was to assess whether RYGB affects the expression of genes related to the intestinal folate metabolism pathway as an additional molecular mechanism contributing to its postoperative deficiency.

METHODS

Biopsies from the duodenum, jejunum, and ileum of 20 obese women were collected before and 3 mo after RYGB. The expression of genes involved in intestinal folate metabolism was assessed by microarray and reverse transcriptase polymerase chain reaction (RT-qPCR). Folate intake (7-d food record) and plasma levels (electrochemiluminescence) also were measured.

RESULTS

Compared with the preoperative phase, transcriptomic alterations were observed in all intestinal segments studied after RYBG, mainly marked by decreased expression of genes encoding folate transporters/receptors and increased expression of genes involved in folate biosynthesis (P < 0.05). Reduced folate intake and plasma folate levels were also observed simultaneously (P < 0.05). Plasma folate concentrations correlated inversely with intestinal FOLR2 and SHMT2 genes (P < 0.001).

CONCLUSION

The present findings suggested that impaired expression of genes related to intestinal folate metabolism may contribute to the early systemic deficiency after RYGB and highlight a potential transcriptomic reprogramming of the intestine in response to RYGB to compensate for folate depletion induced by this surgical technique.

摘要

目的

Roux-en-Y 胃旁路术(RYGB)可促进持续的体重减轻,而由此产生的新的胃肠道解剖结构可能导致营养缺乏。叶酸缺乏是 RYGB 后最常见的营养缺乏症之一。本研究旨在评估 RYGB 是否会影响与肠道叶酸代谢途径相关的基因表达,作为导致其术后缺乏的另一种分子机制。

方法

收集 20 名肥胖女性术前和 RYGB 术后 3 个月的十二指肠、空肠和回肠活检组织。通过微阵列和逆转录聚合酶链反应(RT-qPCR)评估与肠道叶酸代谢相关的基因表达。还测量了叶酸摄入量(7 天饮食记录)和血浆水平(电化学发光)。

结果

与术前阶段相比,RYBG 后所有研究肠段均观察到转录组改变,主要表现为叶酸转运体/受体编码基因的表达降低,叶酸生物合成相关基因的表达增加(P<0.05)。同时也观察到叶酸的减少的摄入量和血浆叶酸水平(P<0.05)。血浆叶酸浓度与肠道 FOLR2 和 SHMT2 基因呈负相关(P<0.001)。

结论

本研究结果表明,与肠道叶酸代谢相关的基因表达受损可能导致 RYGB 后早期出现全身缺乏,并强调了肠道对 RYGB 的潜在转录组重编程,以补偿该手术技术引起的叶酸缺乏。

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