Publication: Melatonin decreases human adipose tissue insulin sensitivity
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Date
2024-06
Authors
Zambrano, Carolina ; Tena Garitaonaindia, Mireia ; Salmerón, Diego ; Pérez‐Sanz, Fernando ; Tchio, Cynthia ; Picinato, María Cecilia ; Sánchez de Medina, Fermín ; Luján, Juan ; Scheer, Frank A. J. L. ; Saxena, Richa ; Martínez‐Augustin, Olga ; Garaulet, Marta
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Publisher
Wiley
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DOI
https://doi.org/10.1111/jpi.12965
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info:eu-repo/semantics/article
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.12965
Abstract
Melatonin 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.
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Citation
Journal of Pineal Research, 2024;76:e12965
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