Early Life Nutrition Research Unit, Academic Division of Child Health, School of Medicine, University Hospital, The University of Nottingham, Nottingham, UK.
Acta Physiol (Oxf). 2014 Jan;210(1):20-30. doi: 10.1111/apha.12053. Epub 2013 Jan 28.
Hypothermia induced by cold exposure at birth is prevented in sheep by the rapid onset of non-shivering thermogenesis in brown adipose tissue (BAT). Changes in adipose tissue composition in early life are therefore essential for survival but also influence adiposity in later life and were thus examined in detail during early development.
Changes in adipose composition were investigated by immunohistochemistry and qRT-PCR between the period from the first appearance of adipose in the mid gestation foetus, through birth and up to 1 month of age.
We identified four distinct phases of development, each associated with pronounced changes in tissue histology and in distribution of the BAT specific uncoupling protein (UCP)1. At mid gestation, perirenal adipose tissue exhibited a dense proliferative, structure marked by high expression of KI-67 but with no UCP1 or visible lipid droplets. By late gestation large quantities of UCP1 were present, lipid storage was evident and expression of BAT-related genes were abundant (e.g. prolactin and β3 receptors). Subsequently, within 12 h of birth, the depot was largely depleted of lipid and expression of genes such as UCP1, PGC1α, CIDEA peaked. By 30 days UCP1 was undetectable and the depot contained large lipid droplets; however, genes characteristic of BAT (e.g. PRDM16 and BMP7) and most characteristic of white adipose tissue (e.g. leptin and RIP140) were still abundant.
Adipose tissue undergoes profound compositional changes in early life, of which an increased understanding could offer potential interventions to retain BAT in later life.
在绵羊中,通过棕色脂肪组织(BAT)中不颤抖产热的快速启动,可以防止出生时因暴露于寒冷而导致的体温过低。因此,生命早期脂肪组织组成的变化对于生存至关重要,但也会影响后期的肥胖,因此在早期发育过程中对其进行了详细研究。
通过免疫组织化学和 qRT-PCR,在从中孕期胎儿首次出现脂肪到出生和 1 个月龄期间,研究脂肪组成的变化。
我们确定了四个不同的发育阶段,每个阶段都与组织学和 BAT 特异性解偶联蛋白(UCP)1 的分布的显著变化相关。在中孕期,肾周脂肪组织表现出密集的增殖结构,其特征是高表达 KI-67,但没有 UCP1 或可见的脂质滴。到了晚孕期,大量的 UCP1 存在,脂质储存明显,与 BAT 相关的基因表达丰富(例如,催乳素和β3 受体)。随后,在出生后 12 小时内,该储存库几乎耗尽了脂质,UCP1 等基因的表达达到峰值,PGC1α、CIDEA 等基因的表达达到峰值。到 30 天时,UCP1 无法检测到,储存库中含有大量的脂质滴;然而,BAT 特有的基因(例如,PRDM16 和 BMP7)和最典型的白色脂肪组织基因(例如,瘦素和 RIP140)仍然丰富。
脂肪组织在生命早期经历了深刻的组成变化,对其深入了解可能为以后保留 BAT 提供潜在的干预措施。