Gastric bypass elicits persistent gut adaptation and unique diabetes remission-related metabolic gene regulation

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Obesity Pub Date : 2024-10-15 DOI:10.1002/oby.24135
Margaret A. Stefater-Richards, Courtney Panciotti, Valerie Esteva, Miriam Lerner, Carter R. Petty, William F. Gourash, Anita P. Courcoulas
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Abstract

Objective

We have previously shown that early intestinal adaptation precedes and relates to metabolic improvement in humans after Roux-en-Y gastric bypass surgery (RYGB). We hypothesized that intestinal adaptation would persist at the 1-year postoperative time point and that gene expression (GE) signatures would relate to type 2 diabetes remission, providing insight into potential mechanisms for intestinally mediated metabolic improvement after RYGB.

Methods

We determined GE by RNA sequencing in jejunum (Roux limb [RL]) collected from 28 patients before and 12 months after RYGB.

Results

Global GE from paired baseline and 1-year jejunal samples did not separate according to clinical phenotype (type 2 diabetes remission, sustained weight loss). In general, GE was consistent with persistent RL remodeling, and microvilli were elongated by 39%. Remodeling was not attenuated in patients with lack of diabetes remission or with weight regain. Patients with diabetes remission demonstrated greater jejunal activation of lipogenesis-related pathways driven by RXR, LXR, and SREBP.

Conclusions

RL adaptation is a key feature of RYGB in all patients, likely reflecting the dramatic alterations to gastrointestinal anatomy, but jejunal lipogenesis appears to be more strongly activated in those patients with diabetes remission. Further study is needed to understand whether these pathways may drive metabolic remission after RYGB.

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胃旁路术可引起持续的肠道适应和独特的糖尿病缓解相关代谢基因调控。
目的:我们以前的研究表明,人类在接受 Roux-en-Y 胃旁路手术(RYGB)后,肠道的早期适应先于代谢改善,而且与代谢改善有关。我们假设肠道适应将持续到术后 1 年,并且基因表达(GE)特征将与 2 型糖尿病缓解相关,从而深入了解 RYGB 术后肠道介导的代谢改善的潜在机制:我们通过 RYGB 前和 RYGB 后 12 个月收集的 28 名患者空肠(Roux 肢端 [RL])的 RNA 测序确定了 GE:结果:从配对的基线和1年空肠样本中获得的全局GE并未根据临床表型(2型糖尿病缓解、体重持续下降)而有所区别。总体而言,GE 与持续的 RL 重塑一致,微绒毛拉长了 39%。在糖尿病未缓解或体重反弹的患者中,重塑作用并未减弱。糖尿病缓解患者的空肠在RXR、LXR和SREBP的驱动下激活了更多的脂肪生成相关途径:结论:RL适应是所有患者RYGB的一个主要特征,可能反映了胃肠道解剖结构的巨大变化,但糖尿病缓解患者的空肠脂肪生成似乎被更强烈地激活。要了解这些途径是否会推动 RYGB 后的代谢缓解,还需要进一步研究。
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来源期刊
Obesity
Obesity 医学-内分泌学与代谢
CiteScore
11.70
自引率
1.40%
发文量
261
审稿时长
2-4 weeks
期刊介绍: Obesity is the official journal of The Obesity Society and is the premier source of information for increasing knowledge, fostering translational research from basic to population science, and promoting better treatment for people with obesity. Obesity publishes important peer-reviewed research and cutting-edge reviews, commentaries, and public health and medical developments.
期刊最新文献
Issue Information Cardiometabolic characteristics of weight cycling: results from a mid-South regional comprehensive health care system Early changes in the gut microbiota are associated with weight outcomes over 2 years following metabolic and bariatric surgery In silico and functional analysis identifies key gene networks and novel gene candidates in obesity-linked human visceral fat Machine learning-based clustering identifies obesity subgroups with differential multi-omics profiles and metabolic patterns
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