Keshava Hari B, Mowla Ashkan, Heinberg Leslie J, Schauer Philip R, Brethauer Stacy A, Aminian Ali
Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Cleveland, OH, United States.
Department of Neurology, Gates Vascular Institute, State University of New York (SUNY) at Buffalo, Buffalo, NY, United States.
Med Hypotheses. 2017 Jul;104:4-9. doi: 10.1016/j.mehy.2017.05.002. Epub 2017 May 3.
Obesity and diabetes are associated with deficits in multiple neurocognitive domains and increased risk for dementia. Over the last two decades, there has been a significant increase in bariatric and metabolic surgery worldwide, driven by rising intertwined pandemics of obesity and diabetes, along with improvement in surgical techniques. Patients undergoing bariatric surgery achieve a significant decrease in their excess weight and a multitude of sequela associated with obesity, diabetes, and metabolic syndrome. Glucagon-like peptide 1 (GLP-1) is an intestinal peptide that has been implicated as one of the weight loss-independent mechanisms in how bariatric surgery affects type 2 diabetes. GLP-1 improves insulin secretion, inhibits apoptosis and induce pancreatic islet neogenesis, promotes satiety, and can regulate heart rate and blood pressure. Moreover, numerous studies have demonstrated potential neuroprotective and neurotrophic effects of GLP-1. Increased GLP-1 activity has been shown to increase cortical activity, promote neuronal growth, and inhibit neuronal degeneration. Specifically, in experimental studies on Alzheimer's disease, GLP-1 decreases amyloid deposition and neurofibrillary tangles. Furthermore, recent studies have also suggested that GLP-1 based therapies, new class of antidiabetic drugs, have favorable effects on neurodegenerative disorders such as Alzheimer's disease. We present a hypothesis that bariatric surgery can help delay or even prevent the onset of Alzheimer's disease in long-term by increasing the levels of GLP-1. This hypothesis has a potential for many studies from basic science projects to large population studies to fully understand the neurological and cognitive consequences of bariatric surgery and associated rise in GLP-1.
肥胖和糖尿病与多个神经认知领域的缺陷以及患痴呆症的风险增加有关。在过去二十年中，受肥胖和糖尿病交织流行情况不断加剧以及手术技术改进的推动，全球范围内减肥和代谢手术显著增加。接受减肥手术的患者体重显著减轻，与肥胖、糖尿病和代谢综合征相关的一系列后遗症也有所减少。胰高血糖素样肽1（GLP-1）是一种肠道肽，被认为是减肥手术影响2型糖尿病的与体重减轻无关的机制之一。GLP-1可改善胰岛素分泌、抑制细胞凋亡并诱导胰岛新生，促进饱腹感，还能调节心率和血压。此外，大量研究已证明GLP-1具有潜在的神经保护和神经营养作用。已表明GLP-1活性增加可增强皮质活动、促进神经元生长并抑制神经元变性。具体而言，在关于阿尔茨海默病的实验研究中，GLP-1可减少淀粉样蛋白沉积和神经原纤维缠结。此外，最近的研究还表明，基于GLP-1的疗法，即一类新型抗糖尿病药物，对诸如阿尔茨海默病等神经退行性疾病具有有益作用。我们提出一个假设，即减肥手术可通过提高GLP-1水平长期帮助延缓甚至预防阿尔茨海默病的发病。这一假设具有很大潜力，可开展从基础科学项目到大规模人群研究等众多研究，以充分了解减肥手术的神经学和认知后果以及GLP-1水平的相应升高。
