{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:40:06Z","timestamp":1790779206786,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Plan Estatal I+D+I from the Spanish Instituto de Salud Carlos III\u2013Subdirecci\u00f3n General de Evaluaci\u00f3n y Fomento de la investigaci\u00f3n\u2013FEDER","doi-asserted-by":"publisher","award":["PI19\/00785"],"award-info":[{"award-number":["PI19\/00785"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Plan Estatal I+D+I from the Spanish Instituto de Salud Carlos III\u2013Subdirecci\u00f3n General de Evaluaci\u00f3n y Fomento de la investigaci\u00f3n\u2013FEDER","doi-asserted-by":"publisher","award":["PI20\/00080"],"award-info":[{"award-number":["PI20\/00080"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Plan Estatal I+D+I from the Spanish Instituto de Salud Carlos III\u2013Subdirecci\u00f3n General de Evaluaci\u00f3n y Fomento de la investigaci\u00f3n\u2013FEDER","doi-asserted-by":"publisher","award":["PI20\/00927"],"award-info":[{"award-number":["PI20\/00927"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CIBEROBN, ISCIII, Spain","award":["PI19\/00785"],"award-info":[{"award-number":["PI19\/00785"]}]},{"name":"CIBEROBN, ISCIII, Spain","award":["PI20\/00080"],"award-info":[{"award-number":["PI20\/00080"]}]},{"name":"CIBEROBN, ISCIII, Spain","award":["PI20\/00927"],"award-info":[{"award-number":["PI20\/00927"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Netrin (NTN)-1 exhibits pro- and anti-inflammatory roles in different settings, playing important roles in the obesity-associated low-grade chronic inflammation. We aimed to determine the impact of NTN-1 on obesity and obesity-associated type 2 diabetes, as well as its role in visceral adipose tissue (VAT) inflammation. A total of 91 subjects were enrolled in this case-control study. Circulating levels of NTN-1 and its receptor neogenin (NEO)-1 were determined before and after weight loss achieved by caloric restriction and bariatric surgery. mRNA levels of NTN1 and NEO1 were assessed in human VAT, liver, and peripheral blood mononuclear cells. In vitro studies in human visceral adipocytes and human monocytic leukemia cells (THP-1)-derived macrophages were performed to analyze the impact of inflammation-related mediators on the gene expression levels of NTN1 and its receptor NEO1 as well as the effect of NTN-1 on inflammation. Increased (p &lt; 0.001) circulating concentrations of NTN-1 in obesity decreased (p &lt; 0.05) after diet-induced weight loss being also associated with a reduction in glucose (p &lt; 0.01) and insulin levels (p &lt; 0.05). Gene expression levels of NTN1 and NEO1 were upregulated (p &lt; 0.05) in the VAT from patients with obesity with the highest expression in the stromovascular fraction cells compared with mature adipocytes (p &lt; 0.01). NTN1 expression levels were enhanced (p &lt; 0.01) under hypoxia and by inflammatory factors in both adipocytes and macrophages. Adipocyte-conditioned media strongly upregulated (p &lt; 0.001) the mRNA levels of NTN1 in macrophages. The treatment of adipocytes with NTN-1 promoted the upregulation (p &lt; 0.05) of pro-inflammatory and chemotactic molecules as well as its receptor NEO1. Collectively, these findings suggest that NTN-1 regulates VAT chronic inflammation and insulin resistance in obesity.<\/jats:p>","DOI":"10.3390\/nu14204372","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:58:51Z","timestamp":1666141131000},"page":"4372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Netrin-1 Promotes Visceral Adipose Tissue Inflammation in Obesity and Is Associated with Insulin Resistance"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6409-7513","authenticated-orcid":false,"given":"Amaia","family":"Mentxaka","sequence":"first","affiliation":[{"name":"Metabolic Research Laboratory, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5601-1604","authenticated-orcid":false,"given":"Javier","family":"G\u00f3mez-Ambrosi","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratory, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III, 31008 Pamplona, Spain"},{"name":"Obesity and Adipobiology Group, Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratory, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III, 31008 Pamplona, Spain"},{"name":"Obesity and Adipobiology Group, Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2180-461X","authenticated-orcid":false,"given":"Amaia","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratory, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III, 31008 Pamplona, Spain"},{"name":"Obesity and Adipobiology Group, Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3441-1970","authenticated-orcid":false,"given":"Sara","family":"Becerril","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratory, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III, 31008 Pamplona, Spain"},{"name":"Obesity and Adipobiology Group, Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Neira","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratory, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor","family":"Valent\u00ed","sequence":"additional","affiliation":[{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III, 31008 Pamplona, Spain"},{"name":"Obesity and Adipobiology Group, Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"},{"name":"Department of Surgery, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Moncada","sequence":"additional","affiliation":[{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III, 31008 Pamplona, Spain"},{"name":"Obesity and Adipobiology Group, Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"},{"name":"Department of Anesthesia, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilo","family":"Silva","sequence":"additional","affiliation":[{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III, 31008 Pamplona, Spain"},{"name":"Department of Endocrinology & Nutrition, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, 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Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8305-7154","authenticated-orcid":false,"given":"Gema","family":"Fr\u00fchbeck","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratory, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III, 31008 Pamplona, Spain"},{"name":"Obesity and Adipobiology Group, Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"},{"name":"Department of Endocrinology & Nutrition, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7513-7509","authenticated-orcid":false,"given":"Victoria","family":"Catal\u00e1n","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratory, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III, 31008 Pamplona, Spain"},{"name":"Obesity and Adipobiology Group, Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"GBD 2015 Obesity Collaborators, Afshin, A., Forouzanfar, M.H., Reitsma, M.B., Sur, P., Estep, K., Lee, A., Marczak, L., Mokdad, A.H., and Moradi-Lakeh, M. 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