Seron-Ferre Maria, Reynolds Henry, Mendez Natalia Andrea, Mondaca Mauricio, Valenzuela Francisco, Ebensperger Renato, Valenzuela Guillermo J, Herrera Emilio A, Llanos Anibal J, Torres-Farfan Claudia
Facultad de Medicina, Laboratorio de Cronobiología, Instituto de Ciencias Biomédicas (ICBM), Universidad de Chile , Santiago , Chile ; Programa de Fisiopatología, Facultad de Medicina, Instituto de Ciencias Biomédicas (ICBM), Universidad de Chile , Santiago , Chile.
Facultad de Medicina, Laboratorio de Cronobiología del Desarrollo, Universidad Austral de Chile , Valdivia , Chile.
Front Endocrinol (Lausanne). 2015 Jan 6;5:232. doi: 10.3389/fendo.2014.00232. eCollection 2014.
In human and sheep newborns, brown adipose tissue (BAT) accrued during fetal development is used for newborn thermogenesis. Here, we explored the role of maternal melatonin during gestation on the amount and functionality of BAT in the neonate. We studied BAT from six lambs gestated by ewes exposed to constant light from 63% gestation until delivery to suppress melatonin (LL), six lambs gestated by ewes exposed to LL but receiving daily oral melatonin (12 mg at 1700 h, LL + Mel) and another six control lambs gestated by ewes maintained in 12 h light:12 h dark (LD). Lambs were instrumented at 2 days of age. At 4-6 days of age, they were exposed to 24°C (thermal neutrality conditions) for 1 h, 4°C for 1 h, and 24°C for 1 h. Afterward, lambs were euthanized and BAT was dissected for mRNA measurement, histology, and ex vivo experiments. LL newborns had lower central BAT and skin temperature under thermal neutrality and at 4°C, and higher plasma norepinephrine concentration than LD newborns. In response to 4°C, they had a pronounced decrease in skin temperature and did not increase plasma glycerol. BAT weight in LL newborns was about half of that of LD newborns. Ex vivo, BAT from LL newborns showed increased basal lipolysis and did not respond to NE. In addition, expression of adipogenic/thermogenic genes (UCP1, ADBR3, PPARγ, PPARα, PGC1α, C/EBPβ, and perilipin) and of the clock genes Bmal1, Clock, and Per2 was increased. Remarkably, the effects observed in LL newborns were absent in LL + Mel newborns. Thus, our results support that maternal melatonin during gestation is important in determining amount and normal functionality of BAT in the neonate.
在人类和绵羊新生儿中，胎儿发育期间积累的棕色脂肪组织（BAT）用于新生儿产热。在此，我们探讨了孕期母体褪黑素对新生儿BAT数量和功能的作用。我们研究了6只母羊从妊娠63%期至分娩期间持续光照以抑制褪黑素（LL）所产羔羊的BAT，6只母羊暴露于持续光照但每日口服褪黑素（1700时12毫克，LL + Mel）所产羔羊的BAT，以及另外6只母羊维持12小时光照：12小时黑暗（LD）条件下所产对照羔羊的BAT。羔羊在2日龄时进行仪器植入。在4 - 6日龄时，将它们暴露于24°C（热中性条件）1小时、4°C 1小时、24°C 1小时。之后，对羔羊实施安乐死并解剖BAT用于mRNA测量、组织学和离体实验。LL组新生儿在热中性和4°C条件下的中央BAT和皮肤温度较低，且血浆去甲肾上腺素浓度高于LD组新生儿。对4°C刺激的反应中，他们的皮肤温度显著下降且血浆甘油未增加。LL组新生儿的BAT重量约为LD组新生儿的一半。在离体实验中，LL组新生儿的BAT基础脂解增加且对去甲肾上腺素无反应。此外，脂肪生成/产热基因（UCP1、ADBR3、PPARγ、PPARα、PGC1α、C/EBPβ和围脂滴蛋白）以及生物钟基因Bmal1、Clock和Per2的表达增加。值得注意的是，LL + Mel组新生儿未出现LL组新生儿中观察到的效应。因此，我们的结果支持孕期母体褪黑素对决定新生儿BAT的数量和正常功能很重要。
