Ramos-Zavala María Guadalupe, García-Galindo Jesús Jonathan, Beltrán-Ramírez Alberto, Balleza-Alejandri Luis Ricardo, Peña-Durán Emiliano, Huerta-Huerta Alfredo, Rubio-Arellano Edy David, López-Murillo Luis Daniel, Pascoe-Gonzalez Sara, Campos-Bayardo Tannia Isabel, Suárez-Rico Daniel Osmar
Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara, Mexico.
Institute of Experimental and Clinical Therapeutics (INTEC), Health Science University Center, Universidad de Guadalajara, Guadalajara, Mexico.
Front Pharmacol. 2025 Aug 28;16:1632956. doi: 10.3389/fphar.2025.1632956. eCollection 2025.
Obesity-driven low-grade inflammation contributes to insulin resistance (IR) and metabolic dysfunction. Beyond its axon-guidance role, Netrin-1 promotes macrophage retention in inflamed adipose tissue, whereas adiponectin exerts anti-inflammatory, insulin-sensitizing effects. We aimed to compare serum Netrin-1, interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and adiponectin across metabolic profiles and assess their associations with systemic inflammation.
We conducted an analytical cross-sectional study in adults (n = 60): metabolically healthy controls (C, n = 20), preclinical obesity (PO; HOMA-IR < 2.5, n = 20), and clinical obesity with insulin resistance (CO; HOMA-IR>2.5, n = 20). Anthropometrics, fasting glucose/insulin, lipid profile, and serum biomarkers were obtained; group differences and correlations were analyzed (non-parametric tests where appropriate).
Between-group testing showed higher Netrin-1 in CO versus controls (Kruskal-Wallis p = 0.013; C < CO), with no significant difference versus PO. IL-6 was elevated in both PO and CO versus controls (Kruskal-Wallis p < 0.001). hs-CRP peaked in PO versus both C and CO (Kruskal-Wallis p < 0.001). Adiponectin was lower in CO and inversely correlated with hs-CRP (r = -0.22) and IL-6 (r = -0.53, p < 0.001).
Circulating Netrin-1 and adiponectin display opposing profiles aligned with pro- versus anti-inflammatory signaling in metabolic dysfunction. These findings support the Netrin-1/adiponectin axis as an immunometabolic marker set in early IR states. The cross-sectional design limits causal inference; longitudinal studies integrating tissue-level measurements are warranted.
肥胖引发的低度炎症会导致胰岛素抵抗（IR）和代谢功能障碍。除了其轴突导向作用外，Netrin-1还能促进巨噬细胞在炎症脂肪组织中的滞留，而脂联素则具有抗炎、胰岛素增敏作用。我们旨在比较不同代谢状况下血清Netrin-1、白细胞介素-6（IL-6）、高敏C反应蛋白（hs-CRP）和脂联素水平，并评估它们与全身炎症的关联。
我们对60名成年人进行了一项分析性横断面研究：代谢健康对照组（C组，n = 20）、临床前肥胖组（PO组；HOMA-IR < 2.5，n = 20）和伴有胰岛素抵抗的临床肥胖组（CO组；HOMA-IR>2.5，n = 20）。获取人体测量数据、空腹血糖/胰岛素、血脂谱和血清生物标志物；分析组间差异和相关性（适当情况下采用非参数检验）。
组间测试显示，CO组的Netrin-1水平高于对照组（Kruskal-Wallis检验，p = 0.013；C组 < CO组），与PO组无显著差异。PO组和CO组的IL-6水平均高于对照组（Kruskal-Wallis检验，p < 0.001）。PO组的hs-CRP水平在与C组和CO组相比时达到峰值（Kruskal-Wallis检验，p < 0.001）。CO组的脂联素水平较低，且与hs-CRP呈负相关（r = -0.22），与IL-6呈负相关（r = -0.53，p < 0.001）。
循环中的Netrin-1和脂联素呈现出相反的变化趋势，与代谢功能障碍中的促炎和抗炎信号一致。这些发现支持Netrin-1/脂联素轴作为早期IR状态下的一种免疫代谢标志物组合。横断面设计限制了因果推断；有必要进行整合组织水平测量的纵向研究。
