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利拉鲁肽治疗肥胖患者可改变巨噬细胞表型并降低其肿瘤坏死因子α释放及氧化应激标志物——一项初步研究

Liraglutide Therapy in Obese Patients Alters Macrophage Phenotype and Decreases Their Tumor Necrosis Factor Alpha Release and Oxidative Stress Markers-A Pilot Study.

作者信息

Bułdak Łukasz, Bołdys Aleksandra, Skudrzyk Estera, Machnik Grzegorz, Okopień Bogusław

机构信息

Department of Internal Medicine and Clinical Pharmacology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Medyków 18, 40-752 Katowice, Poland.

出版信息

Metabolites. 2024 Oct 16;14(10):554. doi: 10.3390/metabo14100554.

Abstract

: Obesity is one of the major healthcare challenges. It affects one in eight people around the world and leads to several comorbidities, including type 2 diabetes, hyperlipidemia, and arterial hypertension. GLP-1 analogs have become major players in the therapy of obesity, leading to significant weight loss in patients. However, benefits resulting from their usage seem to be greater than simple appetite reduction and glucose-lowering potential. Recent data show better cardiovascular outcomes, which are connected with the improvements in the course of atherosclerosis. Macrophages are crucial cells in the forming and progression of atherosclerotic lesions. Previously, it was shown that in vitro treatment with GLP-1 analogs can affect macrophage phenotype, but there is a paucity of in vivo data. : To evaluate the influence of in vivo treatment with liraglutide on basic phenotypic and functional markers of macrophages. : Basic phenotypic features were assessed (including inducible nitric oxide synthase, arginase 1 and mannose receptors), proinflammatory cytokine (IL-1β, TNFα) release, and oxidative stress markers (reactive oxygen species, malondialdehyde) in macrophages obtained prior and after 3-month therapy with liraglutide in patients with obesity. : Three-month treatment with subcutaneous liraglutide resulted in the alteration of macrophage phenotype toward alternative activation (M2) with accompanying reduction in the TNFα release and diminished oxidative stress markers. : Our results show that macrophages in patients treated with GLP-1 can alter their phenotype and function. Those findings may at least partly explain the pleiotropic beneficial cardiovascular effects seen in subjects treated with GLP-1 analogs.

摘要

肥胖是主要的医疗保健挑战之一。它影响着全球八分之一的人口,并导致多种合并症,包括2型糖尿病、高脂血症和动脉高血压。胰高血糖素样肽-1(GLP-1)类似物已成为肥胖治疗的主要药物,可使患者显著减重。然而,其使用带来的益处似乎不止于简单的食欲降低和降血糖潜力。最近的数据显示,其心血管结局更好,这与动脉粥样硬化进程的改善有关。巨噬细胞是动脉粥样硬化病变形成和发展中的关键细胞。此前有研究表明,GLP-1类似物体外处理可影响巨噬细胞表型,但体内数据较少。

目的

评估利拉鲁肽体内治疗对巨噬细胞基本表型和功能标志物的影响。

方法

评估肥胖患者在接受利拉鲁肽3个月治疗前后获得的巨噬细胞的基本表型特征(包括诱导型一氧化氮合酶、精氨酸酶1和甘露糖受体)、促炎细胞因子(IL-1β、TNFα)释放以及氧化应激标志物(活性氧、丙二醛)。

结果

皮下注射利拉鲁肽3个月治疗导致巨噬细胞表型向替代性活化(M2)转变,同时TNFα释放减少,氧化应激标志物降低。

结论

我们的结果表明,接受GLP-1治疗患者的巨噬细胞可改变其表型和功能。这些发现可能至少部分解释了接受GLP-1类似物治疗的受试者出现的多效性心血管有益效应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f5e/11509483/ec23337e072b/metabolites-14-00554-g001.jpg

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