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近日，加拿大卢西奈山卫生系统Daniel J. Drucker及其研究组发现，激活中枢胰高血糖素样肽1受体可抑制Toll样受体激动剂诱发的炎症。该研究于2023年12月18日在线发表于国际一流学术期刊《细胞—代谢》。

研究人员发现胰高血糖素样肽-1受体（GLP-1R）激活可减轻多种Toll样受体激动剂对血浆肿瘤坏死因子α（TNF-α）的诱导。这些作用并非由造血或内皮GLP-1R介导，而是需要中枢神经GLP-1R的参与。在多微生物败血症的盲肠浆液模型中，胰高血糖素样肽-1受体激动剂（GLP-1RA）同样需要神经元GLP-1R来减轻与败血症相关的有害反应，包括疾病、低体温、全身炎症和肺损伤。

从机理上讲，GLP-1R激活可通过α1-肾上腺素能、δ-阿片和κ-阿片受体信号传导导致TNF-α降低。这些数据扩展了新出现的大脑-免疫网络概念，并提出了抑制外周炎症的新的肠道-大脑GLP-1R轴。

据悉，GLP-1RA具有与2型糖尿病慢性并发症相关的抗炎作用。虽然GLP-1RA直接通过肠道上皮内淋巴细胞GLP-1R减轻T细胞介导的肠道和全身炎症，但在GLP-1R没有广泛免疫表达的情况下，GLP-1R如何抑制全身炎症仍不确定。

附：英文原文

Title: Central glucagon-like peptide 1 receptor activation inhibits Toll-like receptor agonist-induced inflammation

Author: Chi Kin Wong, Brent A. McLean, Laurie L. Baggio, Jacqueline A. Koehler, Rola Hammoud, Nikolaj Rittig, Julian M. Yabut, Randy J. Seeley, Theodore J. Brown, Daniel J. Drucker

Issue&Volume: 2023-12-18

Abstract: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) exert anti-inflammatory effectsrelevant to the chronic complications of type 2 diabetes. Although GLP-1RAs attenuateT cell-mediated gut and systemic inflammation directly through the gut intraepitheliallymphocyte GLP-1R, how GLP-1RAs inhibit systemic inflammation in the absence of widespreadimmune expression of the GLP-1R remains uncertain. Here, we show that GLP-1R activationattenuates the induction of plasma tumor necrosis factor alpha (TNF-α) by multipleToll-like receptor agonists. These actions are not mediated by hematopoietic or endothelialGLP-1Rs but require central neuronal GLP-1Rs. In a cecal slurry model of polymicrobialsepsis, GLP-1RAs similarly require neuronal GLP-1Rs to attenuate detrimental responsesassociated with sepsis, including sickness, hypothermia, systemic inflammation, andlung injury. Mechanistically, GLP-1R activation leads to reduced TNF-α via α1-adrenergic, δ-opioid, and κ-opioid receptor signaling. These data extend emergingconcepts of brain-immune networks and posit a new gut-brain GLP-1R axis for suppressionof peripheral inflammation.

DOI: 10.1016/j.cmet.2023.11.009

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00420-5

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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