Lomax Michael A, Sadiq Fouzia, Karamanlidis Georgios, Karamitri Angeliki, Trayhurn Paul, Hazlerigg David G
Division of Biomedical Science, Imperial College, Ashford, Kent TN25 5AH, UK.
Endocrinology. 2007 Jan;148(1):461-8. doi: 10.1210/en.2006-0918. Epub 2006 Oct 5.
In ruminants and other large animals, expression of uncoupling protein-1 (UCP1) in brown adipose tissue (BAT) is confined to the perinatal period when it plays a key role in nonshivering thermogenesis. This study determined whether loss of expression of the BAT phenotype was due to reduced response to a beta-agonist, isoprenaline, and expression of the peroxisome proliferator-activated receptor (PPAR) family [PPARalpha, PPARgamma, PPAR coactivator 1alpha (PGC-1alpha)], which regulates UCP1 gene expression. Perirenal adipose tissue (PAT) was sampled from ovine fetuses, newborn lambs, and lambs on d 1, 5, 7, and 21 of life. UCP1 mRNA and protein in PAT increased from d 123 of fetal life to reach a maximum at birth followed by a rapid decrease over the first 5 d of life. Expression of the coactivator, PGC-1alpha and PPAR alpha, peaked between fetal day 123 and birth, and then declined to undetectable levels in the first days of life. In vivo administration of isoprenaline was able to induce expression of UCP1, PGC-1alpha, and PPARalpha in BAT up to 5 d of age but thereafter was ineffective. In vitro addition of beta-receptor, PPARalpha, and PPARgamma agonists were unable to overcome the suppression of UCP1, PPARalpha, and PPARgamma expression observed in differentiated adipocytes prepared from 30-d-old compared with 1-d-old lambs. These data are consistent with a model in which postnatal loss of UCP1 expression and beta-adrenergic induction of the brown adipocyte phenotype is due to loss of expression of PGC-1alpha and PPARalpha.
在反刍动物和其他大型动物中，棕色脂肪组织（BAT）中解偶联蛋白-1（UCP1）的表达仅限于围产期，此时它在非颤抖性产热中起关键作用。本研究确定BAT表型表达的丧失是否是由于对β-激动剂异丙肾上腺素的反应降低，以及过氧化物酶体增殖物激活受体（PPAR）家族[PPARα、PPARγ、PPAR共激活因子1α（PGC-1α）]的表达降低，该家族调节UCP1基因的表达。从绵羊胎儿、新生羔羊以及出生后第1、5、7和21天的羔羊采集肾周脂肪组织（PAT）。PAT中UCP1的mRNA和蛋白从胎儿期第123天开始增加，在出生时达到最大值，随后在出生后的前5天迅速下降。共激活因子PGC-1α和PPARα的表达在胎儿期第123天至出生之间达到峰值，然后在出生后的头几天降至无法检测的水平。在出生后5天龄以内，体内给予异丙肾上腺素能够诱导BAT中UCP1、PGC-1α和PPARα的表达，但此后无效。与1日龄羔羊相比，体外添加β受体、PPARα和PPARγ激动剂无法克服在30日龄羔羊分化脂肪细胞中观察到的UCP1、PPARα和PPARγ表达的抑制。这些数据与一个模型一致，即出生后UCP1表达的丧失和棕色脂肪细胞表型的β-肾上腺素能诱导是由于PGC-1α和PPARα表达的丧失。
