哺乳动物的繁殖是一个昂贵的生理过程，母体需要花费很大的能量代价。繁殖过程中，动物的体温调节和能量代谢等生理学过程都会发生较大的变化。中国科学院动物研究所王德华研究组以内蒙古草原的野生布氏田鼠为研究对象，近几年集中研究了繁殖期的产热和能量代谢特征及其机理，最近有较大进展。
在妊娠期和哺乳期，布氏田鼠都表现出摄食量增加和适应性产热受到抑制的现象，然而1994年发现的由脂肪组织分泌的调节体重的激素－瘦素(leptin)，其对母体产热和能量代谢的生理功能在两个时期是不同的。妊娠期瘦素水平较高，但并没有抑止动物的摄食，失去了“饱食信号”的作用，暗示可能发生了瘦素抵抗现象。在哺乳期，血清瘦素水平较低，此期动物的摄食量也增加，说明瘦素可能充当了“饥饿信号”的作用。进一步研究发现，在妊娠期瘦素抵抗的形成与下丘脑瘦素的长型受体（Ob-Rb）的表达降低和控制瘦素作用敏感性的细胞因子信号抑制子-3（suppressor-of-cytokine-signaling-3，SOCS-3）的表达升高有关。下丘脑抑止摄食的神经肽POMC（proopiomelanocortin）的表达下调可能是导致妊娠布氏田鼠摄食增加的原因之一。通过施加外源瘦素处理实验进一步证明，哺乳期低水平的瘦素水平可以增加下丘脑的两种促进摄食的神经肽NPY （neuropeptide Y）和AgRP （agouti-related protein）的表达量，降低POMC的表达，来促进动物的摄食量和抑制动物的产热能力。无论是妊娠期还是哺乳期，当动物受到低温刺激时，血清瘦素的浓度没有发生明显变化，但能量摄入和褐色脂肪组织线粒体内膜上的解偶联蛋白－1(uncoupling protein 1，UCP1)的表达却显著增加，表明布氏田鼠能够通过提高产热能力和增加摄食量来应对寒冷和繁殖的双重压力，瘦素在寒冷环境条件下对能量代谢的调控作用与常温条件下不同。一些与冷有关的应激激素如去甲肾上腺素、皮质酮等可能也参与了对动物摄食和产热的调节，同时这些激素与瘦素之间可能存在互作作用。
相关研究成果发表在《实验生物学杂志》（Journal of Experimental Biology）(2007，210: 512-521) 、《比较生物化学与生理学C》（Comparative Biochemistry and Physiology C）（2008，148 : 390–400.）和《神经内分泌学杂志》（Journal of Neuroendocrinology）(2008，20:1038-44)等刊物上。（生物谷Bioon.com）
生物谷推荐原始出处：
Journal of Neuroendocrinology，Volume 20 Issue 9, Pages 1038 - 1044，G.-B. Tang，D.-H. Wang
Hypothalamic Suppressor-of-Cytokine-Signalling 3 mRNA is Elevated and Pro-Opiomelanocortin mRNA is Reduced During Pregnancy in Brandt's Voles (Lasiopodomys brandtii )
G.-B. Tang*?, J.-G. Cui*? and D.-H. Wang*
1State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Datun Lu, Chaoyang, Beijing, China.
2Graduate School of the Chinese Academy of Sciences, Yuquan Lu, Beijing, China.
ABSTRACT
Leptin acts within the hypothalamus to diminish food intake. In Brandt's voles (Lasiopodomys brandtii), both circulating leptin levels and food intake are elevated during pregnancy, suggesting an ineffectiveness of leptin to reduce food intake. Diminished hypothalamic leptin receptors and impaired leptin signal transduction are characteristic of central leptin resistance. The present study aimed to determine whether these characteristic modulations of leptin sensitivity occurred in pregnant Brandt's voles. The mRNA expression of the long form of the leptin receptor (Ob-Rb), suppressor-of-cytokine-signalling 3 (SOCS3), neuropeptide Y (NPY), agouti-related protein (AgRP), pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) in the hypothalamus were examined on dioestrous, day 5, day 10 and day 18 of pregnancy. Compared to controls, there was no significant change in hypothalamic Ob-Rb mRNA during the pregnancy. SOCS3 mRNA was increased significantly by 68% on day 10% and 93% on day 18 of pregnancy compared to controls. Despite elevated leptin levels, POMC mRNA was decreased significantly by 60% on day 18 of pregnancy, whereas no differences were found in the mRNA expression of NPY, AgRP and CART in pregnant voles compared to controls. The elevation of SOCS3 mRNA together with disrupted leptin regulation of neuropeptides in the hypothalamus suggests that leptin resistance may develop in pregnant Brandt's voles.
