Gnanalingham M G, Mostyn A, Wang J, Webb R, Keisler D H, Raver N, Alves-Guerra M C, Pecqueur C, Miroux B, Stephenson T, Symonds M E
Centre for Reproduction and Early Life, Institute of Clinical Research, University of Nottingham, Nottingham NG7 2UH, UK.
J Endocrinol. 2005 Oct;187(1):81-8. doi: 10.1677/joe.1.06251.
Many tissues undergo a rapid transition after birth, accompanied by dramatic changes in mitochondrial protein function. In particular, uncoupling protein (UCP) abundance increases at birth in the lung and adipose tissue, to then gradually decline, an adaptation that is important in enabling normal tissue function. Leptin potentially mediates some of these changes and is known to promote the loss of UCP1 from brown fat but its effects on UCP2 and related mitochondrial proteins (i.e. voltage-dependent anion channel (VDAC) and cytochrome c) in other tissues are unknown. We therefore determined the effects of once-daily jugular venous administration of ovine recombinant leptin on mitochondrial protein abundance as determined by immunoblotting in tissues that do (i.e. the brain and pancreas) and do not (i.e. liver and skeletal muscle) express UCP2. Eight pairs of 1-day-old lambs received either 100 mug leptin or vehicle daily for 6 days, before tissue sampling on day 7. Administration of leptin diminished UCP2 abundance in the pancreas, but not the brain. Leptin administration had no affect on the abundance of VDAC or cytochrome c in any tissue examined. In leptin-administered animals, but not controls, UCP2 abundance in the pancreas was positively correlated with VDAC and cytochrome c content, and UCP2 abundance in the brain with colonic temperature. In conclusion, leptin administration to neonatal lambs causes a tissue-specific loss of UCP2 from the pancreas. These effects may be important in the regulation of neonatal tissue development and potentially for optimising metabolic control mechanisms in later life.
许多组织在出生后会经历快速转变，同时线粒体蛋白功能也会发生显著变化。特别是，解偶联蛋白（UCP）在出生时肺和脂肪组织中的丰度增加，随后逐渐下降，这种适应性变化对正常组织功能的实现很重要。瘦素可能介导了其中一些变化，已知它会促进棕色脂肪中UCP1的丢失，但其对其他组织中UCP2及相关线粒体蛋白（即电压依赖性阴离子通道（VDAC）和细胞色素c）的影响尚不清楚。因此，我们通过免疫印迹法测定了每天经颈静脉注射一次绵羊重组瘦素对表达UCP2的组织（即脑和胰腺）以及不表达UCP2的组织（即肝脏和骨骼肌）中线粒体蛋白丰度的影响。八对1日龄羔羊每天接受100微克瘦素或载体注射，持续6天，然后在第7天进行组织采样。注射瘦素可降低胰腺中UCP2的丰度，但对脑无影响。注射瘦素对所检测的任何组织中VDAC或细胞色素c的丰度均无影响。在注射瘦素的动物中，而非对照组中，胰腺中UCP2的丰度与VDAC和细胞色素c的含量呈正相关，而脑中UCP2的丰度与结肠温度呈正相关。总之，给新生羔羊注射瘦素会导致胰腺中UCP2出现组织特异性丢失。这些影响可能对新生儿组织发育的调节很重要，并且可能有助于优化后期生活中的代谢控制机制。
