Tang Gang-Bin, Cui Jian-Guo, Wang De-Hua
State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Chaoyang, Beijing.
Am J Physiol Regul Integr Comp Physiol. 2009 Nov;297(5):R1293-301. doi: 10.1152/ajpregu.00185.2009. Epub 2009 Sep 2.
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 degrees 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 degrees 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.
布氏田鼠（Lasiopodomys brandtii）会通过大幅增加非颤抖性产热来应对长期寒冷暴露，从而导致代偿性摄食过量和脂肪动员。这些生理过程伴随着血清瘦素水平的显著降低。然而，低瘦素血症在该物种冷适应中的作用仍不清楚。在本研究中，我们检验了这样一个假设，即低瘦素血症通过改变冷暴露布氏田鼠下丘脑神经肽来促进食物摄入量增加和棕色脂肪组织（BAT）产热。成年雄性田鼠被转移到5摄氏度环境中28天。伴随着血清瘦素水平下降，下丘脑刺鼠相关蛋白（AgRP）mRNA水平显著升高，但下丘脑瘦素受体长型（Ob-Rb）、细胞因子信号抑制因子3（SOCS3）、神经肽Y（NPY）mRNA、阿黑皮素原（POMC）以及可卡因和苯丙胺调节肽（CART）mRNA水平没有变化。当冷暴露田鼠回到温暖环境（23摄氏度）28天后，体重、食物摄入量、血清瘦素和AgRP mRNA恢复到对照水平。给冷暴露田鼠注射瘦素会降低食物摄入量以及下丘脑AgRP mRNA水平。在寒冷条件下，注射瘦素对下丘脑Ob-Rb、SOCS3、NPY、POMC、CART mRNA以及解偶联蛋白1水平没有显著影响。这些结果表明，低瘦素血症部分促成了寒冷诱导的摄食过量，这可能涉及下丘脑AgRP基因表达的升高。
