van Tuijl Julia, Vreeken Debby, Broeders Wieteke, Cossins Benjamin, van Emst Liesbeth, Seidel Florine, Stienstra Rinke, Li Yang, Joosten Leo A B, Netea Mihai G, Hazebroek Eric J, Kleemann Robert, Kiliaan Amanda J, Bekkering Siroon, Riksen Niels P
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Medical Imaging, Anatomy, Radboud Alzheimer Center, Donders Institute for Brain Cognition and Behaviour, Center of Medical Neuroscience, Nijmegen, the Netherlands.
Int J Obes (Lond). 2025 Aug 20. doi: 10.1038/s41366-025-01886-3.
Obesity is an important risk factor for atherosclerotic cardiovascular disease. This cardiovascular risk remains increased even after substantial weight loss by bariatric surgery. Innate immune cells are important regulators of atherogenesis and can adopt a long-term hyperinflammatory phenotype via epigenetic reprogramming, called "trained immunity". In this translational observational case-cohort study, we investigated the persistence of innate immune cell hyperresponsiveness following bariatric surgery, and explored the potential contribution of adipose tissue in ex vivo models.
SUBJECTS/METHODS: In a cohort of 27 patients with obesity blood was drawn before and six months after bariatric surgery, and compared to 20 healthy subjects with normal body weight. We assessed monocytes using flow cytometry, functional assays, and RNA sequencing and chromatin immunoprecipitation. In an accompanying series of in vitro studies, healthy donor monocytes were exposed for 24 h to adipose tissue obtained from patients with obesity during bariatric surgery. Cytokine production capacity was assessed after one week.
In our case-cohort study, although leukocyte numbers and systemic inflammatory markers such as hs-CRP decreased after bariatric surgery to the level of normal weight control subjects, the hyperresponsive pro-inflammatory monocyte phenotype was only partially reverted six months after bariatric surgery, which aligned with the RNA expression profiles. Exposure of monocytes to adipose tissue obtained from patients with obesity induces a persistent augmented cytokine production capacity.
Although in patients with obesity, six months after bariatric surgery systemic inflammatory markers and leukocyte numbers are decreased to the levels observed in healthy lean subjects, there is still a residual functional and transcriptional hyper-inflammatory monocyte phenotype. This might be caused, at least in part, by the capacity of adipose tissue to induce long-term pro-inflammatory effects in monocytes. These finding help to understand the long-term effects of obesity and bariatric surgery on cardiovascular health.
肥胖是动脉粥样硬化性心血管疾病的重要危险因素。即使在接受减肥手术后体重大幅减轻，这种心血管风险仍然增加。固有免疫细胞是动脉粥样硬化形成的重要调节因子，可通过表观遗传重编程呈现长期的高炎症表型，即“训练有素的免疫”。在这项转化性观察性病例队列研究中，我们调查了减肥手术后固有免疫细胞高反应性的持续性，并在体外模型中探讨了脂肪组织的潜在作用。
受试者/方法：在一组27例肥胖患者中，于减肥手术前和术后6个月采集血液，并与20例体重正常的健康受试者进行比较。我们使用流式细胞术、功能测定、RNA测序和染色质免疫沉淀法评估单核细胞。在一系列配套的体外研究中，将健康供体的单核细胞暴露于减肥手术期间从肥胖患者获取的脂肪组织中24小时。一周后评估细胞因子产生能力。
在我们的病例队列研究中，尽管减肥手术后白细胞数量和hs-CRP等全身炎症标志物降至正常体重对照受试者的水平，但促炎单核细胞的高反应性表型在减肥手术后6个月仅部分恢复，这与RNA表达谱一致。单核细胞暴露于肥胖患者的脂肪组织会诱导持续增强的细胞因子产生能力。
尽管肥胖患者在减肥手术后6个月全身炎症标志物和白细胞数量降至健康瘦受试者的水平，但仍存在残余的功能性和转录性高炎症单核细胞表型。这可能至少部分是由于脂肪组织在单核细胞中诱导长期促炎作用的能力所致。这些发现有助于理解肥胖和减肥手术对心血管健康的长期影响。
