Gnanalingham M G, Mostyn A, Webb R, Keisler D H, Raver N, Alves-Guerra M C, Pecqueur C, Miroux B, Symonds M E, Stephenson T
Centre for Reproduction and Early Life, Institute of Clinical Research, University of Nottingham, Nottingham NG7 2UH, UK.
Am J Physiol Endocrinol Metab. 2005 Dec;289(6):E1093-100. doi: 10.1152/ajpendo.00228.2005. Epub 2005 Aug 9.
In the neonate, adipose tissue and the lung both undergo a rapid transition after birth, which results in dramatic changes in uncoupling protein abundance and glucocorticoid action. Leptin potentially mediates some of these adaptations and is known to promote the loss of uncoupling protein (UCP)1, but its effects on other mitochondrial proteins or glucocorticoid action are not known. We therefore determined the effects of acute and chronic administration of ovine recombinant leptin on brown adipose tissue (BAT) and/or lung in neonatal sheep. For the acute study, eight pairs of 1-day-old lambs received, sequentially, 10, 100, and 100 mug of leptin or vehicle before tissue sampling 4 h from the start of the study, whereas in the chronic study, nine pairs of 1-day-old lambs received 100 mug of leptin or vehicle daily for 6 days before tissue sampling on day 7. Acute leptin decreased the abundance of UCP2, glucocorticoid receptor, and 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 mRNA and increased 11beta-HSD type 2 mRNA abundance in BAT, a pattern that was reversed with chronic leptin administration, which also diminished lung UCP2 protein abundance. In BAT, UCP2 mRNA abundance was positively correlated to plasma leptin and nonesterified fatty acids and negatively correlated to mean colonic temperature in the leptin group at 7 days. In conclusion, leptin administration to the neonatal lambs causes differential effects on UCP2 abundance in BAT and lung. These effects may be important in the development of these tissues, thereby optimizing lung function and fat growth.
在新生儿中，脂肪组织和肺在出生后都会经历快速转变，这导致解偶联蛋白丰度和糖皮质激素作用发生显著变化。瘦素可能介导了其中一些适应性变化，并且已知其会促进解偶联蛋白（UCP）1的减少，但其对其他线粒体蛋白或糖皮质激素作用的影响尚不清楚。因此，我们确定了急性和慢性给予绵羊重组瘦素对新生绵羊棕色脂肪组织（BAT）和/或肺的影响。在急性研究中，八对1日龄羔羊在研究开始后4小时进行组织采样前，依次接受10、100和100微克的瘦素或载体，而在慢性研究中，九对1日龄羔羊在第7天进行组织采样前，连续6天每天接受100微克的瘦素或载体。急性给予瘦素会降低BAT中UCP2、糖皮质激素受体和1型11β-羟基类固醇脱氢酶（11β-HSD）mRNA的丰度，并增加2型11β-HSD mRNA的丰度，这种模式在慢性给予瘦素后会逆转，慢性给予瘦素还会降低肺UCP2蛋白的丰度。在BAT中，UCP2 mRNA丰度与瘦素组第7天的血浆瘦素和非酯化脂肪酸呈正相关，与平均结肠温度呈负相关。总之，给新生羔羊注射瘦素会对BAT和肺中的UCP2丰度产生不同影响。这些影响可能对这些组织的发育很重要，从而优化肺功能和脂肪生长。
