Department of Pharmacology and Neurosciences Institute, School of Medicine & Biomedical Research Center, University of Granada, 18016 Granada, Spain.
Department of Pediatrics, School of Medicine, University of Granada (Spain). Unit of Pediatric Neurology and Neurodevelopment, Clínico San Cecilio University Hospital, the Andalusian Health Service, Granada, Spain.
Food Funct. 2022 Mar 21;13(6):3760-3775. doi: 10.1039/d1fo04360a.
The role of melatonin in obesity control is extensively accepted, but its mechanism of action is still unclear. Previously we demonstrated that chronic oral melatonin acts as a brown-fat inducer, driving subcutaneous white adipose tissue (sWAT) into a brown-fat-like function (beige) in obese diabetic rats. However, immunofluorescence characterization of beige depots in sWAT and whether melatonin is a beige-fat inducer by differentiation and/or transdifferentiation of white adipocytes are still undefined. Lean (ZL) and diabetic fatty (ZDF) Zücker rats were subdivided into two groups, control (C) and oral melatonin-supplemented (M, 10 mg kg day) for 6 weeks. Mesenchymal stem cells (MSCs) were isolated from both rat inguinal fat and human lipoaspirates followed by adipogenesis assays with or without melatonin (50 nM for 12 h in a 24 h period, 12 h+/12 h-) mimicking the light/dark cycle. Immunofluorescence and western-blot assays showed the partial transdifferentiation of white adipocytes in both ZL and ZDF rats, with increasing thermogenic and beige markers, UCP1 and CITED1 and decreasing white adipocyte marker ASC-1 expression. In addition, melatonin increased UCP1, CITED1, and PGC1-α expression in differentiated adipocytes in both rats and humans. These results demonstrate that melatonin increases brown fat in obese diabetic rats by both adipocyte transdifferentiation and differentiation. Furthermore, it promotes beige MSC adipogenesis in humans. This may contribute to the control of body weight attributed to melatonin and its metabolic benefits in human diabesity.
褪黑素在肥胖控制中的作用已被广泛接受，但它的作用机制仍不清楚。我们之前的研究表明，慢性口服褪黑素可作为棕色脂肪诱导剂，使肥胖糖尿病大鼠的皮下白色脂肪组织（sWAT）向棕色脂肪样功能（米色）转变。然而，sWAT 中米色脂肪的免疫荧光特征，以及褪黑素是否通过白色脂肪细胞的分化和/或转分化诱导米色脂肪，仍然不明确。瘦鼠（ZL）和糖尿病肥胖鼠（ZDF）被分为两组，对照组（C）和口服褪黑素补充组（M，10mg/kg/天），共 6 周。从大鼠腹股沟脂肪和人脂肪抽吸物中分离间充质干细胞（MSCs），然后进行脂肪生成实验，有或没有褪黑素（50 nM，24 小时内 12 小时/12 小时），模拟光/暗周期。免疫荧光和 Western blot 检测显示，ZL 和 ZDF 大鼠的白色脂肪细胞发生部分转分化，增加了产热和米色标记物 UCP1 和 CITED1，减少了白色脂肪细胞标记物 ASC-1 的表达。此外，褪黑素增加了两种大鼠和人类分化脂肪细胞中 UCP1、CITED1 和 PGC1-α 的表达。这些结果表明，褪黑素通过脂肪细胞转分化和分化增加肥胖糖尿病大鼠的棕色脂肪。此外，它还促进了人类米色 MSC 脂肪生成。这可能有助于控制归因于褪黑素的体重，并在人类肥胖症中带来代谢益处。
