ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Inflammation Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1632956
This article is part of the Research TopicTherapeutic Effects of Endogenous Hormones in Pathologies Linked to Metabolic and/or Inflammatory DisordersView all 6 articles
Opposing Profiles of Netrin-1 and Adiponectin in Metabolic Inflammation and Insulin Resistance
Provisionally accepted- 1Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, México, Guadalajara, Mexico
- 2Institute of Experimental and Clinical Terapeutics (INTEC), Health Science University Center, Universidad de Guadalajara, 44340, Mexico, Guadalajara, Mexico
- 3Hospital Medica de la Ciudad, Santa Catalina, Calle. Pablo Valdez 719, La Perla, Guadalajara 44360, Guadalajara, Mexico
- 4Licenciatura en Médico Cirujano y Partero, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara, Mexico
- 5Institute of Experimental and Clinical Terapeutics (INTEC), Health Science University Center, Universidad de Guadalajara, 44340, Guadalajara, Mexico
- 6División de Medicina Molecular, Laboratorio de Microbiología Molecular II, CIBO, IMSS, Ap. Postal 1-3838, Guadalajara, Mexico
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Obesity is associated with chronic low-grade inflammation that contributes to the development of insulin resistance and metabolic dysfunction. Recent evidence suggests that Netrin-1, originally described as an axonal guidance molecule, also plays a role in immune regulation by promoting macrophage retention in inflamed adipose tissue. This study aimed to evaluate the serum concentrations of Netrin-1, interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and adiponectin in individuals with different metabolic profiles-non-obese controls, individuals with preclinical obesity, and individuals with clinical obesity and insulin resistance-and to explore their association with systemic inflammation and early metabolic disturbances. Methods: Cross-sectional study between 2023 and 2024 including 60 participants, control group (C, n = 20) comprised individuals aged 18-35 years with body-fat percentages < 25 % in men and < 35 % in women and a body-mass index (BMI) < 25 kg/m². The two remaining groups were classified according to their Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) score into preclinical obesity (PO, HOMA-IR < 2.5; n = 20) and clinical obesity with insulin resistance (CO, HOMA-IR > 2.5; n = 20). Anthropometric indices, fasting glucose/insulin and lipid panel were recorded. Serum Netrin1, adiponectin, IL6 and hsCRP were quantified by sandwich ELISA. Pairwise Wilcoxon tests with Holm correction were performed as post hoc analysis following Kruskal-Wallis; correlations were assessed using Spearman coefficients with 95% confidence intervals. Results: Netrin-1 levels were significantly elevated in participants with obesity and insulin resistance compared to controls (p = 0.013) and showed a positive correlation with hs-CRP (r = 0.34, p < 0.05). In contrast, adiponectin levels declined progressively across groups (p < 0.001) and had an inverse correlation with body fat percentage (r = -0.52), waist circumference (r = -0.43), IL-6 (r = -0.53), and hs-CRP (r = -0.22). Additionally, a negative correlation was observed between Netrin-1 and adiponectin (r = -0.39), suggesting a possible counter-regulatory relationship. Conclusion: These findings indicate that Netrin-1 and adiponectin exhibit opposing behaviors in relation to metabolic impairment and inflammation, positioning them as potential biomarkers and therapeutic targets in the early stages of metabolic disease.
Keywords: Netrin-1, Adiponectin, Insulin Resistance, Obesity, Inflammation, Macrophages, Hs-CRP, IL-6
Received: 21 May 2025; Accepted: 04 Aug 2025.
Copyright: © 2025 Ramos-Zavala, García-Galindo, Beltrán-Ramírez, Balleza-Alejandri, Peña-Durán, Huerta, Rubio Arellano, López-Murillo, Pascoe-Gonzalez, Campos Bayardo and Suárez Rico. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jesus Jonathan García-Galindo, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, México, Guadalajara, Mexico
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