Schmid Andreas, Wilfurth Emily, Höpfinger Alexandra, Behrendt Manuel, Islami Edita, Karrasch Thomas, Berghoff Martin, Schäffler Andreas
Department of Internal Medicine III, Giessen University Hospital, Giessen, Germany.
Department of Neurology, Giessen University Hospital, Klinikstraße 33, 35392, Gießen Giessen, Germany.
Sci Rep. 2025 Aug 17;15(1):30138. doi: 10.1038/s41598-025-14846-8.
GDF15 (growth/differentiation factor-15) belongs to the superfamily of transforming growth factor-beta. Little is known about adipocytic regulation of GDF15, its concentrations in serum and cerebrospinal fluid (CSF), its permeability to the brain, and its correlation with neurological diseases. This knowledge is important for a potential and clinical role of GDF15 as a mediator of the fat-brain axis in metabolic and neurological diseases. GDF15 mRNA expression in 3T3-L1 adipocytes was measured by qPCR and GDF15 protein levels in supernatants, serum and CSF were determined by ELISA. In vitro, GDF15 expression is nearly absent in pre-adipocytes and strongly upregulated during adipocyte differentiation. Insulin upregulates GDF15 secretion in adipocytes under normo- and hyperglycemic conditions. In vivo, we quantified GDF15 protein concentrations in paired samples of serum and CSF in a large and well-characterized clinical cohort of n = 390 patients undergoing neurological investigation and spinal puncture. This broad data set could serve as a basis for the development of GDF15 reference values in serum and CSF. GDF15 is highly permeable to the brain according to a specific CSF / serum ratio of 306 × 10. GDF15 is significantly increased in overweight and type 2 diabetic patients and correlates positively with serum glucose and HbA. GDF15 in CSF is elevated in patients with increased CSF cell count and impaired blood-brain-barrier function. Among five subsets of neurological diagnoses, GDF15 is exclusively increased in CSF and serum of patients with infectious diseases. GDF15 represents a promising adipokine and mediator of the fat-brain-axis that is co-regulated with metabolic factors and elevated in neurological patients with infectious diseases.
生长分化因子15（GDF15）属于转化生长因子-β超家族。关于GDF15的脂肪细胞调控、其在血清和脑脊液（CSF）中的浓度、其对脑的通透性以及其与神经系统疾病的相关性，人们了解甚少。这些知识对于GDF15作为代谢和神经系统疾病中脂肪-脑轴介质的潜在和临床作用至关重要。通过qPCR检测3T3-L1脂肪细胞中GDF15 mRNA的表达，并通过ELISA测定上清液、血清和CSF中GDF15蛋白水平。在体外，前脂肪细胞中几乎不存在GDF15表达，而在脂肪细胞分化过程中其表达强烈上调。在正常血糖和高血糖条件下，胰岛素上调脂肪细胞中GDF15的分泌。在体内，我们在一个由n = 390例接受神经学检查和腰椎穿刺的患者组成的大型且特征明确的临床队列中，对配对的血清和CSF样本中的GDF15蛋白浓度进行了定量。这个广泛的数据集可作为血清和CSF中GDF15参考值制定基础。根据306×10的特定CSF /血清比值，GDF15对脑具有高度通透性。超重和2型糖尿病患者的GDF15显著增加，且与血糖和糖化血红蛋白呈正相关。CSF细胞计数增加和血脑屏障功能受损的患者CSF中的GDF15升高。在神经诊断的五个亚组中，GDF15仅在传染病患者的CSF和血清中升高。GDF15是一种有前景的脂肪因子和脂肪-脑轴介质，与代谢因子共同调节，在患有传染病的神经疾病患者中升高。
