{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:41:33Z","timestamp":1791236493245,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T00:00:00Z","timestamp":1718064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Melatonin is a pineal hormone that modulates the circadian system and exerts soporific and phase\u2010shifting effects. It is also involved in many other physiological processes, such as those implicated in cardiovascular, endocrine, immune, and metabolic functions. However, the role of melatonin in glucose metabolism remains contradictory, and its action on human adipose tissue (AT) explants has not been demonstrated. We aimed to assess whether melatonin (a pharmacological dose) influences insulin sensitivity in human AT. This will help better understand melatonin administration's effect on glucose metabolism. Abdominal AT (subcutaneous and visceral) biopsies were obtained from 19 participants with severe obesity (age: 42.84\u2009\u00b1\u200912.48 years; body mass index: 43.14\u2009\u00b1\u20098.26\u2009kg\/m<jats:sup>2<\/jats:sup>) who underwent a laparoscopic gastric bypass. AT biopsies were exposed to four different treatments: control (C), insulin alone (I) (10\u2009nM), melatonin alone (M) (5000\u2009pg\/mL), and insulin plus melatonin combined (I\u2009+\u2009M). All four conditions were repeated in both subcutaneous and visceral AT, and all were performed in the morning at 8 a.m. (<jats:italic>n<\/jats:italic>\u2009=\u200919) and the evening at 8 p.m. (in a subsample of <jats:italic>n<\/jats:italic>\u2009=\u200912). We used western blot analysis to determine insulin signaling (using the pAKT\/tAKT ratio). Furthermore, RNAseq analyses were performed to better understand the metabolic pathways involved in the effect of melatonin on insulin signaling. As expected, insulin treatment (I) increased the pAKT\/tAKT ratio compared with control (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001). Furthermore, the addition of melatonin (I\u2009+\u2009M) resulted in a decrease in insulin signaling as compared with insulin alone (I); this effect was significant only during the evening time (not in the morning time). Further, RNAseq analyses in visceral AT during the evening condition (at 8 p.m.) showed that melatonin resulted in a prompt transcriptome response (around 1\u2009h after melatonin addition), particularly by downregulating the insulin signaling pathway. Our results show that melatonin reduces insulin sensitivity in human AT during the evening. These results may partly explain the previous studies showing a decrease in glucose tolerance after oral melatonin administration in the evening or when eating late when endogenous melatonin is present.<\/jats:p>","DOI":"10.1111\/jpi.12965","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T10:32:29Z","timestamp":1718101949000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Melatonin decreases human adipose tissue insulin sensitivity"],"prefix":"10.1111","volume":"76","author":[{"given":"Carolina","family":"Zambrano","sequence":"first","affiliation":[{"name":"Department of Physiology, Regional Campus of International Excellence University of Murcia Murcia Spain"},{"name":"Research Biomedical Institute of Murcia (IMIB)\u2010Arrixaca Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireia Tena","family":"Garitaonaindia","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology II, Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), Ibs Granada, Instituto de Nutrici\u00f3n y Tecnolog\u00eda de los Alimentos (INYTA) Jos\u00e9 Mataix University of Granada Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Salmer\u00f3n","sequence":"additional","affiliation":[{"name":"Research Biomedical Institute of Murcia (IMIB)\u2010Arrixaca Murcia Spain"},{"name":"Health and Social Sciences Department University of Murcia Murcia Spain"},{"name":"Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP) Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"P\u00e9rez\u2010Sanz","sequence":"additional","affiliation":[{"name":"Research Biomedical Institute of Murcia (IMIB)\u2010Arrixaca Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Tchio","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Massachusetts General Hospital Cambridge Massachusetts USA"},{"name":"Department of Anesthesia, Critical Care and Pain Medicine Massachusetts General Hospital and Harvard Medical School Boston Massachusetts USA"},{"name":"Department of Medical and Population Genetics Broad Institute of MIT and Harvard Cambridge Massachusetts USA"},{"name":"Cardiovascular Research Institute, Morehouse School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Cecilia","family":"Picinato","sequence":"additional","affiliation":[{"name":"University Federal do Oeste da Bahia Barreiras Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferm\u00edn S\u00e1nchez","family":"de Medina","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), Ibs Granada Universidad de Granada Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Luj\u00e1n","sequence":"additional","affiliation":[{"name":"General Surgery Service, Hospital Quir\u00f3nsalud Murcia Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank A. 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