面临寒冷环境的胁迫，动物从生理和行为上进行一系列调整以应对由于产热能力增加而导致能量需求的增加。在此过程中，作为能量平衡的两个重要方面——摄食和产热均呈现复杂而精细的调控。中国科学院动物研究所动物生理生态学研究组以栖息在内蒙古草原的野生布氏田鼠为研究对象，以在能量代谢调控中发挥关键作用的瘦素(leptin)为切入点，对其在冷适应中的作用机制进行了研究。

布氏田鼠（Lasiopodomys brandtii）是栖息在内蒙古高原上的一种植食性啮齿动物，其分布区冬季严寒而漫长，年温差和昼夜温差都较大，冬季最低温可达负40摄氏度，这对一种体型只有50克左右的小型恒温动物是一个严酷的挑战。布氏田鼠有许多对策适应严冬，如群居，储存食物，群聚效应。冬季非颤抖性产热（一种不需要收缩肌肉就产生热能的有效方式）增加，食物摄入增加，还动用身体脂肪存积。体重也具有明显的季节变化，一般模式是冬季体重趋向于降低，减少总的能量需求。这个过程伴随着血液瘦素水平的变化。但是，瘦素浓度冬季（寒冷季节降低）的生理地位是什么呢？一直不是很清楚。本研究中的工作假设是：低浓度的瘦素对于食物摄入增加和BAT产热能力增加是有贡献的，并且可能是通过调整下丘脑的神经肽的变化来进行调节作用的。

将成年的布氏田鼠从温暖环境(23摄氏度)转入寒冷环境（5摄氏度）中，驯化4周，结果发现：在冷驯化过程中，伴随着瘦素水平的降低，下丘脑增食类神经肽AgRP （agouti-related protein）的表达显著增加，而瘦素的长型受体（Ob-Rb）、细胞信号抑制因子SOCS3 （suppressor-of-cytokine-signaling 3）、增食类神经肽NPY （neuropeptide Y）、厌食类神经肽POMC （proopiomelanocortin）和CART （cocaine- and amphetamine-regulated peptide)）的表达均没有显著变化。当将冷环境中驯化的田鼠转回到温暖环境中中时，动物的体重、食物摄入，血清瘦素水平和AgRP mRNA表达等都会恢复到对照组的水平。

为了验证这一发现，对布氏田鼠进行施加外源瘦素。用微渗透泵定量控制瘦素的分泌速率。经外源瘦素处理后，在冷驯化条件下布氏田鼠的摄食量明显减少，下丘脑AgRP和褐色脂肪组织BAT线粒体内膜上的解偶联蛋白1（uncoupling protein 1, UCP1）的表达也明显降低，统计发现AgRP和摄食量呈现显著的相关关系。在整个瘦素信号作用通路上的其它分子如Ob-Rb、SOCS3、NPY、POMC和CART 的表达则没有受到外源瘦素处理的影响。这些结果表明，与常温条件下相比，在寒冷环境中瘦素水平对动物的摄食水平和产热能力的调控机制发生了改变，根据分析认为，神经肽AgRP在这个调节过程中可能扮演了重要角色。当然，这还需要进一步的实验验证。

原始出处：

Am J Physiol Regul Integr Comp Physiol 297: R1293-R1301, 2009. First published September 2, 2009; doi:10.1152/ajpregu.00185.2009

Role of hypoleptinemia during cold adaptation in Brandt's voles (Lasiopodomys brandtii)

Gang-Bin Tang,1,2 Jian-Guo Cui,1,2 and De-Hua Wang1

1State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Chaoyang, Beijing; and 2Graduate School of the Chinese Academy of Sciences, Yuquan Lu, Beijing, China

Brandt's voles Lasiopodomys brandtii exhibit large increases in nonshivering thermogenesis to cope with chronic cold exposure, resulting in compensatory hyperphagia and fat mobilization. These physiological events are accompanied by a remarkable reduction in serum leptin levels. However, the role of hypoleptinemia in cold adaptation in this species is still unknown. In the present study, we tested the hypothesis that hypoleptinemia contributes to increases in food intake and brown adipose tissue (BAT) thermogenesis by modifying hypothalamic neuropeptides in cold-exposed Brandt's voles. Adult male voles were transferred to 5°C for 28 days. Accompanied by a decrease in serum leptin levels, hypothalamic agouti-related protein (AgRP) mRNA levels were significantly increased, but there were no changes in the long form of leptin receptor (Ob-Rb), suppressor of cytokine signaling 3 (SOCS3), neuropeptide Y (NPY) mRNA, proopiomelanocortin (POMC), and cocaine- and amphetamine-regulated peptide (CART) mRNA levels in the hypothalamus. When cold-exposed voles were returned to warm (23°C) for 28 days, body mass, food intake, serum leptin, and AgRP mRNA were restored to control levels. Leptin administration in cold-exposed voles decreased food intake as well as hypothalamic AgRP mRNA levels. There were no significant effects of leptin administration on hypothalamic Ob-Rb, SOCS3, NPY, POMC, CART mRNA, and uncoupling protein 1 levels under cold conditions. These results suggest that hypoleptinemia partially contributes to cold-induced hyperphagia, which might involve the elevation of hypothalamic AgRP gene expression.