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Few studies have examined colostrum from obese mothers, particularly with respect to macrophage function, enzyme and cytokine concentrations, and the role of melatonin in immune modulation. This study aimed to evaluate melatonin levels and their effects on macrophage polarization, cytokine concentrations, nitric oxide synthase [iNOS], and arginase in colostrum from obese mothers. Colostrum samples were collected from eutrophic mothers [BMI: 18.5\u201324.9 kg\/m2] and obese mothers [BMI: \u226530 kg\/m2]. Methods: Macrophages were isolated by density gradient and treated with melatonin. The expression of M1 and M2 macrophages and cytokine concentrations were assessed by flow cytometry, while melatonin levels in colostrum supernatants, iNOS, and arginase in cell lysates were determined by ELISA. Results: An endogenous increase in melatonin was also observed in the colostrum of obese mothers. Maternal obesity has been shown to reduce M1 and M2 macrophage expression, increase nitric oxide synthase [NOS] activity, and elevate interleukin-6 [IL-6] and interleukin-17 [IL-17] levels. However, melatonin treatment restored M1 and M2 macrophage levels and reduced inducible nitric oxide synthase [iNOS] and arginase production to levels similar to those observed in mothers of healthy weight. Conclusions: these findings suggest that maternal obesity creates a pro-inflammatory environment in colostrum, characterized by altered macrophage polarization, altered cytokine secretion, and an imbalance in the enzymatic activities of iNOS and arginase within the L-arginine metabolic pathway. Both natural and supplemental melatonin exhibited immunomodulatory, antioxidant, and anti-inflammatory effects, helping to restore immune balance in colostrum. These results emphasize the potential benefits of melatonin as an immunometabolic modulator and its contribution to understanding immunometabolic regulation in obese mothers.<\/jats:p>","DOI":"10.3390\/metabo16060420","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:49:01Z","timestamp":1781570941000},"page":"420","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Melatonin Modulates Macrophage Polarization and Immunometabolic Responses in the Colostrum of Obese Mothers"],"prefix":"10.3390","volume":"16","author":[{"given":"Silvia Hannah Bilotti Ratto Gomes da","family":"Silva","sequence":"first","affiliation":[{"name":"Institute of Biological and Health Science, Federal University of Mato Grosso, Barra do Gar\u00e7as 78600-000, MT, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4921-4064","authenticated-orcid":false,"given":"Danielle Cristina Honorio","family":"Fran\u00e7a","sequence":"additional","affiliation":[{"name":"Health Sciences Institute, Federal University of Mato Grosso, Sinop 78557-287, MT, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8708-4803","authenticated-orcid":false,"given":"K\u00eania Maria Resende","family":"Silva","sequence":"additional","affiliation":[{"name":"Institute of Biological and Health Science, Federal University of Mato Grosso, Barra do Gar\u00e7as 78600-000, MT, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuelle Carolina Honorio","family":"Fran\u00e7a","sequence":"additional","affiliation":[{"name":"Institute of Biological and Health Science, Federal University of Mato Grosso, Barra do Gar\u00e7as 78600-000, MT, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6863-0971","authenticated-orcid":false,"given":"Viviane Francelina","family":"Luz","sequence":"additional","affiliation":[{"name":"Institute of Biological and Health Science, Federal University of Mato Grosso, Barra do Gar\u00e7as 78600-000, MT, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arce dos Santos","family":"Sfredo","sequence":"additional","affiliation":[{"name":"Institute of Biological and Health Science, Federal University of Mato Grosso, Barra do Gar\u00e7as 78600-000, MT, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5101-2883","authenticated-orcid":false,"given":"Tassiane Cristina","family":"Morais","sequence":"additional","affiliation":[{"name":"School of Sciences, Santa Casa de Misericordia de Vitoria, EMESCAM, Vitoria 29045-402, ES, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1854-5397","authenticated-orcid":false,"given":"Eduardo Luz\u00eda","family":"Fran\u00e7a","sequence":"additional","affiliation":[{"name":"Institute of Biological and Health Science, Federal University of Mato Grosso, Barra do Gar\u00e7as 78600-000, MT, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0452-9804","authenticated-orcid":false,"given":"Adenilda Cristina","family":"Honorio-Fran\u00e7a","sequence":"additional","affiliation":[{"name":"Institute of Biological and Health Science, Federal University of Mato Grosso, Barra do Gar\u00e7as 78600-000, MT, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/s41574-019-0176-8","article-title":"Obesity: Global Epidemiology and Pathogenesis","volume":"15","year":"2019","journal-title":"Nat. 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