Melatonin decreases human adipose tissue insulin sensitivity

IF 8.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Journal of Pineal Research Pub Date : 2024-06-11 DOI:10.1111/jpi.12965
Carolina Zambrano, Mireia Tena Garitaonaindia, Diego Salmerón, Fernando Pérez-Sanz, Cynthia Tchio, María Cecilia Picinato, Fermín Sánchez de Medina, Juan Luján, Frank A. J. L. Scheer, Richa Saxena, Olga Martínez-Augustin, Marta Garaulet
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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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褪黑素会降低人体脂肪组织对胰岛素的敏感性。
褪黑素是一种松果体激素,它能调节昼夜节律系统,并具有催眠和移相作用。它还参与许多其他生理过程,例如与心血管、内分泌、免疫和新陈代谢功能有关的过程。然而,褪黑激素在葡萄糖代谢中的作用仍然存在矛盾,而且它对人体脂肪组织(AT)外植体的作用尚未得到证实。我们的目的是评估褪黑素(药理剂量)是否会影响人体脂肪组织的胰岛素敏感性。这将有助于更好地了解褪黑素对糖代谢的影响。我们从19名接受腹腔镜胃旁路手术的重度肥胖症患者(年龄:42.84 ± 12.48岁;体重指数:43.14 ± 8.26 kg/m2)身上采集了腹部AT(皮下和内脏)活检组织。腹腔镜胃旁路术活检组织接受了四种不同的治疗:对照组(C)、单用胰岛素组(I)(10 nM)、单用褪黑素组(M)(5000 pg/mL)和胰岛素加褪黑素组(I + M)。所有四种情况都在皮下和内脏 AT 中重复进行,并且都在早上 8 点(n = 19)和晚上 8 点(n = 12 的子样本)进行。我们使用 Western 印迹分析来确定胰岛素信号转导(使用 pAKT/tAKT 比值)。此外,我们还进行了 RNAseq 分析,以更好地了解褪黑激素对胰岛素信号转导的影响所涉及的代谢途径。不出所料,与对照组相比,胰岛素处理(I)增加了 pAKT/tAKT 比率(p
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来源期刊
Journal of Pineal Research
Journal of Pineal Research 医学-内分泌学与代谢
CiteScore
17.70
自引率
4.90%
发文量
66
审稿时长
1 months
期刊介绍: The Journal of Pineal Research welcomes original scientific research on the pineal gland and melatonin in vertebrates, as well as the biological functions of melatonin in non-vertebrates, plants, and microorganisms. Criteria for publication include scientific importance, novelty, timeliness, and clarity of presentation. The journal considers experimental data that challenge current thinking and welcomes case reports contributing to understanding the pineal gland and melatonin research. Its aim is to serve researchers in all disciplines related to the pineal gland and melatonin.
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