Department of Medicine 1, University of Kiel, 24105 Kiel, Germany.
Institute of Medical Informatics and Statistics, University of Kiel, 24105 Kiel, Germany.
J Clin Endocrinol Metab. 2018 Nov 1;103(11):4253-4264. doi: 10.1210/jc.2018-01007.
Common nutrition-associated diseases like obesity and type 2 diabetes are linked to chronic low-grade inflammation. The secreted glycopeptide wingless-type mouse mammary tumor virus integration site family member 5a (wnt5a) has been implicated in metabolic inflammation in rodent models, suggesting a potential treatment target. Data on the role of wnt5a in human physiology have yielded conflicting results.
Serum concentrations of wnt5a were measured in a cross-sectional cohort of 896 people to gain deeper insights into wnt5a physiology.
Serum concentrations of wnt5a were measured by ELISA and related to several phenotyping and genotyping data. In vitro experiments were performed in THP-1 macrophages to examine potential molecular mechanisms.
Wnt5a levels were significantly positively correlated to IL-6 and triglyceride levels. In subjects with diabetes, wnt5a levels were elevated and significantly correlated with fasting plasma glucose concentrations. Although wnt5a levels were not influenced by common single-nucleotide polymorphisms in the human wnt5a gene, environmental factors significantly altered wnt5a concentrations, as follows: (1) wnt5a levels were reduced in subjects with high nutritional load of the long-chain eicosatetraenoic acid independent of the total caloric intake and overall composition of the macronutrients, and (2) wnt5a levels were lower in humans with a high gut microbiome α diversity. In vitro experiments revealed that stimulation of the IL-6 receptor or the long-chain fatty acid receptor GPR40 directly affected wnt5a expression in human macrophages.
Our data suggest that wnt5a is important in linking inflammation to metabolism. The nutrition and the microbiome might be interesting targets to prevent and/or treat wnt5a-mediated metabolic inflammation.
肥胖和 2 型糖尿病等常见营养相关疾病与慢性低度炎症有关。分泌的糖肽无翅型小鼠乳腺肿瘤病毒整合位点家族成员 5a（wnt5a）在啮齿动物模型的代谢炎症中起作用，提示其可能是一个潜在的治疗靶点。关于 wnt5a 在人体生理学中的作用的数据得出了相互矛盾的结果。
通过横断面队列研究 896 人，测量 wnt5a 的血清浓度，以更深入地了解 wnt5a 的生理学。
通过 ELISA 测量 wnt5a 的血清浓度，并将其与多种表型和基因型数据相关联。在 THP-1 巨噬细胞中进行体外实验，以研究潜在的分子机制。
Wnt5a 水平与 IL-6 和甘油三酯水平呈显著正相关。在糖尿病患者中，wnt5a 水平升高，并与空腹血糖浓度显著相关。尽管人类 wnt5a 基因中的常见单核苷酸多态性不影响 wnt5a 水平，但环境因素显著改变了 wnt5a 浓度，如下所示：（1）wnt5a 水平在长链二十碳四烯酸的营养负荷高的受试者中降低，而与总热量摄入和宏量营养素的整体组成无关，（2）wnt5a 水平在肠道微生物组 α 多样性高的人群中较低。体外实验表明，IL-6 受体或长链脂肪酸受体 GPR40 的刺激直接影响人巨噬细胞中 wnt5a 的表达。
我们的数据表明，wnt5a 在将炎症与代谢联系起来方面很重要。营养和微生物组可能是预防和/或治疗 wnt5a 介导的代谢炎症的有趣靶点。
