Translational and Integrative Gastrointestinal and Endocrine Research Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA.
Brain Glycemic and Metabolism Control Department, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA.
Mol Metab. 2023 Feb;68:101517. doi: 10.1016/j.molmet.2022.101517. Epub 2022 May 26.
Bariatric or weight loss surgery is currently the most effective treatment for obesity and metabolic disease. Unlike dieting and pharmacology, its beneficial effects are sustained over decades in most patients, and mortality is among the lowest for major surgery. Because there are not nearly enough surgeons to implement bariatric surgery on a global scale, intensive research efforts have begun to identify its mechanisms of action on a molecular level in order to replace surgery with targeted behavioral or pharmacological treatments. To date, however, there is no consensus as to the critical mechanisms involved.
The purpose of this non-systematic review is to evaluate the existing evidence for specific molecular and inter-organ signaling pathways that play major roles in bariatric surgery-induced weight loss and metabolic benefits, with a focus on Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), in both humans and rodents.
Gut-brain communication and its brain targets of food intake control and energy balance regulation are complex and redundant. Although the relatively young science of bariatric surgery has generated a number of hypotheses, no clear and unique mechanism has yet emerged. It seems increasingly likely that the broad physiological and behavioral effects produced by bariatric surgery do not involve a single mechanism, but rather multiple signaling pathways. Besides a need to improve and better validate surgeries in animals, advanced techniques, including inducible, tissue-specific knockout models, and the use of humanized physiological traits will be necessary. State-of-the-art genetically-guided neural identification techniques should be used to more selectively manipulate function-specific pathways.
减重或减肥手术目前是治疗肥胖和代谢疾病最有效的方法。与节食和药理学不同，它在大多数患者中的有益效果可以持续数十年，而且其死亡率在主要手术中是最低的。由于全球范围内进行减重手术的外科医生数量远远不够，因此已经开始进行密集的研究工作，以确定其在分子水平上的作用机制，以便用靶向行为或药物治疗替代手术。然而，迄今为止，对于涉及的关键机制仍没有达成共识。
本非系统性综述的目的是评估特定分子和器官间信号通路在减重手术诱导的体重减轻和代谢益处中的现有证据，重点是 Roux-en-Y 胃旁路术（RYGB）和垂直袖状胃切除术（VSG），在人类和啮齿动物中均有涉及。
肠道-大脑通讯及其作为食物摄入控制和能量平衡调节的大脑靶点是复杂且冗余的。尽管减重手术这一相对年轻的科学已经产生了许多假说，但尚未出现明确和独特的机制。似乎越来越有可能的是，减重手术产生的广泛生理和行为效应并不涉及单一机制，而是多种信号通路。除了需要改进和更好地验证动物手术外，还需要先进的技术，包括诱导型、组织特异性基因敲除模型以及对人类生理特征的利用。应使用最先进的基因引导神经识别技术来更有选择性地操纵特定功能的途径。
