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Melatonin decreases human adipose tissue insulin sensitivity

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dc.contributor.authorZambrano, Carolina
dc.contributor.authorTena Garitaonaindia, Mireia
dc.contributor.authorSalmerón, Diego
dc.contributor.authorPérez‐Sanz, Fernando
dc.contributor.authorTchio, Cynthia
dc.contributor.authorPicinato, María Cecilia
dc.contributor.authorSánchez de Medina, Fermín
dc.contributor.authorLuján, Juan
dc.contributor.authorScheer, Frank A. J. L.
dc.contributor.authorSaxena, Richa
dc.contributor.authorMartínez‐Augustin, Olga
dc.contributor.authorGaraulet, Marta
dc.contributor.departmentCiencias Sociosanitarias
dc.date.accessioned2024-06-14T10:50:33Z
dc.date.available2024-06-14T10:50:33Z
dc.date.issued2024-06
dc.description© 2024 The Author(s). This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/. This document is the Published version of a Published Work that appeared in final form in Journal of Pineal Research. To access the final edited and published work see https://doi.org/10.1111/jpi.12965es
dc.description.abstractMelatonin is a pineal hormone that modulates the circadian system and exerts soporific and phase‐shifting 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 ± 12.48 years; body mass index: 43.14 ± 8.26 kg/m2 ) who underwent a laparoscopic gastric bypass. AT biopsies were exposed to four different treatments: control (C), insulin alone (I) (10 nM), melatonin alone (M) (5000 pg/mL), and insulin plus melatonin combined (I + M). All four conditions were repeated in both subcutaneous and visceral AT, and all were performed in the morning at 8 a.m. (n = 19) and the evening at 8 p.m. (in a subsample of n = 12). 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 (p < .0001). Furthermore, the addition of melatonin (I + M) 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 h 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.es
dc.formatapplication/pdfes
dc.format.extent11es
dc.identifier.citationJournal of Pineal Research, 2024;76:e12965
dc.identifier.doihttps://doi.org/10.1111/jpi.12965
dc.identifier.eissnElectronic: 1600-079X
dc.identifier.issnPrint: 0742-3098
dc.identifier.urihttp://hdl.handle.net/10201/142277
dc.languageenges
dc.publisherWileyes
dc.relationThis work has partly been supported by Grant PID2020‐112768RB‐I00 funded by MCIN/AEI/10.13039/ 501100011033 to Marta Garaulet. Supported in part by The Spanish Government of Investigation, Development and Innovation (PID2020‐120140RB‐I00 OMA) including FEDER co‐funding; Fondo de Investigaciones sanitarias, Instituto de Salud Carlos III, Spain (PI21/00952), co‐funded by European Regional Development Fund/European Social Fund; the Autonomous Community Junta de Andalucía [A‐AGR‐468‐UGR20 and P20‐00695, CTS235, CTS164] to Olga Martínez‐Augustin and Fermín Sánchezde Medina, and NIDDK R01DK105072 to Marta Garaulet. Frank A. J. L. Scheer was supported in part by NIDDK R01DK105072 and NHLBI R01HL140574. Mireia Tena Garitaonaindia were supported by the Ministry of Education [Spain]. CIBERehd is funded by Instituto de Salud Carlos III.es
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectAdipose tissuees
dc.subjectExplantses
dc.subjectInsulin sensitivityes
dc.subjectMelatonines
dc.subjectObesityes
dc.titleMelatonin decreases human adipose tissue insulin sensitivityes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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