title: Impact of Maternal Melatonin Suppression on Amount and Functionality of Brown Adipose Tissue (BAT) in the Newborn Sheep.
abstract: 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.
authors.affiliation: 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.
authors.forename: Maria
authors.initials: M
authors.lastname: Seron-Ferre
authors.affiliation: 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.
authors.forename: Henry
authors.initials: H
authors.lastname: Reynolds
authors.affiliation: Facultad de Medicina, Laboratorio de Cronobiología del Desarrollo, Universidad Austral de Chile , Valdivia , Chile.
authors.forename: Natalia Andrea
authors.initials: NA
authors.lastname: Mendez
authors.affiliation: 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.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Mondaca
authors.affiliation: 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.
authors.forename: Francisco
authors.initials: F
authors.lastname: Valenzuela
authors.affiliation: 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.
authors.forename: Renato
authors.initials: R
authors.lastname: Ebensperger
authors.affiliation: Department of Women's Health, Arrowhead Regional Medical Center , San Bernardino, CA , USA.
authors.forename: Guillermo J
authors.initials: GJ
authors.lastname: Valenzuela
authors.affiliation: Programa de Fisiopatología, Facultad de Medicina, Instituto de Ciencias Biomédicas (ICBM), Universidad de Chile , Santiago , Chile.
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Herrera
authors.affiliation: Programa de Fisiopatología, Facultad de Medicina, Instituto de Ciencias Biomédicas (ICBM), Universidad de Chile , Santiago , Chile.
authors.forename: Anibal J
authors.initials: AJ
authors.lastname: Llanos
authors.affiliation: Facultad de Medicina, Laboratorio de Cronobiología del Desarrollo, Universidad Austral de Chile , Valdivia , Chile.
authors.forename: Claudia
authors.initials: C
authors.lastname: Torres-Farfan
keywords: SCN; circadian; constant light; development; newborn; thermoregulation