面臨寒冷環(huán)境的脅迫,，動(dòng)物從生理和行為上進(jìn)行一系列調(diào)整以應(yīng)對(duì)由于產(chǎn)熱能力增加而導(dǎo)致能量需求的增加,。在此過(guò)程中,，作為能量平衡的兩個(gè)重要方面——攝食和產(chǎn)熱均呈現(xiàn)復(fù)雜而精細(xì)的調(diào)控,。中國(guó)科學(xué)院動(dòng)物研究所動(dòng)物生理生態(tài)學(xué)研究組以棲息在內(nèi)蒙古草原的野生布氏田鼠為研究對(duì)象,，以在能量代謝調(diào)控中發(fā)揮關(guān)鍵作用的瘦素(leptin)為切入點(diǎn),，對(duì)其在冷適應(yīng)中的作用機(jī)制進(jìn)行了研究,。
布氏田鼠（Lasiopodomys brandtii）是棲息在內(nèi)蒙古高原上的一種植食性嚙齒動(dòng)物，其分布區(qū)冬季嚴(yán)寒而漫長(zhǎng),，年溫差和晝夜溫差都較大,，冬季最低溫可達(dá)負(fù)40攝氏度，這對(duì)一種體型只有50克左右的小型恒溫動(dòng)物是一個(gè)嚴(yán)酷的挑戰(zhàn),。布氏田鼠有許多對(duì)策適應(yīng)嚴(yán)冬,，如群居，儲(chǔ)存食物,，群聚效應(yīng),。冬季非顫抖性產(chǎn)熱（一種不需要收縮肌肉就產(chǎn)生熱能的有效方式）增加，食物攝入增加,，還動(dòng)用身體脂肪存積,。體重也具有明顯的季節(jié)變化，一般模式是冬季體重趨向于降低,，減少總的能量需求,。這個(gè)過(guò)程伴隨著血液瘦素水平的變化,。但是,，瘦素濃度冬季（寒冷季節(jié)降低）的生理地位是什么呢？一直不是很清楚,。本研究中的工作假設(shè)是：低濃度的瘦素對(duì)于食物攝入增加和BAT產(chǎn)熱能力增加是有貢獻(xiàn)的,，并且可能是通過(guò)調(diào)整下丘腦的神經(jīng)肽的變化來(lái)進(jìn)行調(diào)節(jié)作用的。
將成年的布氏田鼠從溫暖環(huán)境(23攝氏度)轉(zhuǎn)入寒冷環(huán)境（5攝氏度）中,，馴化4周,，結(jié)果發(fā)現(xiàn)：在冷馴化過(guò)程中，伴隨著瘦素水平的降低,，下丘腦增食類神經(jīng)肽AgRP （agouti-related protein）的表達(dá)顯著增加,，而瘦素的長(zhǎng)型受體（Ob-Rb）、細(xì)胞信號(hào)抑制因子SOCS3 （suppressor-of-cytokine-signaling 3）,、增食類神經(jīng)肽NPY （neuropeptide Y）,、厭食類神經(jīng)肽POMC （proopiomelanocortin）和CART （cocaine- and amphetamine-regulated peptide)）的表達(dá)均沒有顯著變化。當(dāng)將冷環(huán)境中馴化的田鼠轉(zhuǎn)回到溫暖環(huán)境中中時(shí),，動(dòng)物的體重,、食物攝入，血清瘦素水平和AgRP mRNA表達(dá)等都會(huì)恢復(fù)到對(duì)照組的水平,。
為了驗(yàn)證這一發(fā)現(xiàn),，對(duì)布氏田鼠進(jìn)行施加外源瘦素,。用微滲透泵定量控制瘦素的分泌速率。經(jīng)外源瘦素處理后,，在冷馴化條件下布氏田鼠的攝食量明顯減少,，下丘腦AgRP和褐色脂肪組織BAT線粒體內(nèi)膜上的解偶聯(lián)蛋白1（uncoupling protein 1, UCP1）的表達(dá)也明顯降低，統(tǒng)計(jì)發(fā)現(xiàn)AgRP和攝食量呈現(xiàn)顯著的相關(guān)關(guān)系,。在整個(gè)瘦素信號(hào)作用通路上的其它分子如Ob-Rb,、SOCS3、NPY,、POMC和CART 的表達(dá)則沒有受到外源瘦素處理的影響,。這些結(jié)果表明，與常溫條件下相比,，在寒冷環(huán)境中瘦素水平對(duì)動(dòng)物的攝食水平和產(chǎn)熱能力的調(diào)控機(jī)制發(fā)生了改變,，根據(jù)分析認(rèn)為，神經(jīng)肽AgRP在這個(gè)調(diào)節(jié)過(guò)程中可能扮演了重要角色,。當(dāng)然,，這還需要進(jìn)一步的實(shí)驗(yàn)驗(yàn)證。（生物谷Bioon.com）
J.Neuroendocrinology：哺乳動(dòng)物繁殖期產(chǎn)熱和能量代謝研究
生物谷推薦原始出處：
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.
