Early Life Research Unit, Division of Child Health, Obstetrics & Gynaecology, University of Nottingham, Nottingham, UK.
Nottingham Digestive Disease Centre and Biomedical Research Centre, School of Medicine, University of Nottingham, Nottingham, UK.
J Endocrinol. 2021 Jan;248(1):R19-R28. doi: 10.1530/JOE-20-0075.
Adipose tissue is usually laid down in small amounts in the foetus and is characterised as possessing small amounts of the brown adipose tissue-specific mitochondrial uncoupling protein (UCP)1. In adults, a primary factor determining the abundance and function of UCP1 is ambient temperature. Cold exposure causes activation and the rapid generation of heat through the free flow of protons across the mitochondria with no requirement to convert ADP to ATP. In rodents, housing at an ambient temperature below thermoneutrality promotes the appearance of beige like adipocytes. These arise as discrete regions of UCP1 containing cells in white fat depots. There is increasing evidence to show that to gain credible translational results on brown and beige fat function in rodent models that they should be housed at thermoneutrality. This not only reflects the type of environment in which humans spend a majority of their time, but is in accord with the rise of global temperature caused by industrialisation and the uncontrolled burning of fossil fuels. There is now good evidence in adult humans, that stimulating brown fat can improve glucose homeostasis which can be achieved either by nutritional or pharmacological interventions. The challenge, therefore, is to establish credible developmental models in animals maintained at thermoneutrality which will elucidate the true impact of nutrition. The primary focus should fall specifically on the components of breast milk and how these modulate long term effects on brown or beige fat development and function.
脂肪组织通常在胎儿期少量沉积,并具有少量棕色脂肪组织特异性解偶联蛋白 (UCP)1。在成年人中,决定 UCP1 丰度和功能的主要因素是环境温度。寒冷暴露会导致激活,质子通过线粒体自由流动产生热量,而无需将 ADP 转化为 ATP。在啮齿动物中,在环境温度低于热中性的环境中饲养会促进米色脂肪细胞的出现。这些细胞出现在白色脂肪储存器中含有 UCP1 的细胞的离散区域中。越来越多的证据表明,为了在啮齿动物模型中获得关于棕色和米色脂肪功能的可信转化结果,它们应该在热中性温度下饲养。这不仅反映了人类大部分时间所处的环境类型,而且与工业化和不受控制的化石燃料燃烧导致的全球温度上升相一致。现在有充分的证据表明,刺激棕色脂肪可以改善葡萄糖稳态,可以通过营养或药物干预来实现。因此,挑战在于在保持热中性的动物中建立可靠的发育模型,这将阐明营养的真正影响。重点应特别放在母乳的成分上,以及这些成分如何调节对棕色或米色脂肪发育和功能的长期影响。