黑线仓鼠应对环境的能量收支策略：体重和脂肪累积的“调定点”及其能量学机理研究

The adaptive regulations of energy metabolism and the plasticity of body mass and fat accumulation are important biological characters in variety of animals, which is of great significance to increase the opportunities in response to extreme environment. In small mammals, body mass and fat accumulation are increased under some situations but are decreased in other conditions, indicating there may be a “set-point”. However, it is unknown how the “set-point” works, which environmental factors affect it, or how the mechanisms of energy metabolism run. In the present study, the effects of temperature (gradient decrease in temperature and warm), food availability (food shortage and plenty) and predation pressure (the existence or non-existence of predators) on energy metabolism in striped hamsters. The model and energetic characters of the “set-point” have been studied based on integrative measurements of whole organism (energy intake and expenditure), organs and tissues (histology morphology and activity of digestive enzyme), cell (rate of mitochondria respiratory), hormones (serum leptin and corticosterone), molecular (mRNA expression and protein expression of uncoupling protein and neuropeptide) and transcriptomics (RNASeq analysis of different genes expression). We aim to explore the trade-off strategy between the up-regulation and down-regulation of plasticity of body mass and fat accumulation. Further, the mechanisms of energetics, regulation network and molecular mechanisms underlining the plasticity will be elucidated. Finally, the data from this study will help to understand the characters of life history, as well as the survival strategy and adaptive mechanisms in response to environmental changes in small mammals.

能量代谢的适应性调节，以及体重和脂肪累积的可塑性变化是许多动物的重要生物学特征，对其应对极端环境，提高生存机会具有重要意义。在不同环境下小型哺乳动物体重和脂肪累积呈现“上调”和“下调”，暗示“调定点”的存在，然而该“调定点”的模式、影响因素和能量学机制尚不清楚。本项目拟研究温度（梯度低温和暖温）、食物资源（食物短缺和丰富）和捕食压力（被捕食风险存在与否）对黑线仓鼠能量代谢影响，从整体(能量收支等)、器官组织(组织学形态和消化酶活性等)、细胞(线粒体呼吸率等)、激素(血清瘦素和皮质酮水平等)、分子(解偶联蛋白和神经肽基因或蛋白表达等)和转录组学（基因差异表达分析）各个层次整合研究“调定点”模式及能量学特征，旨在阐明动物在体重和脂肪累积可塑性“上调”和“下调”之间的权衡策略，揭示其可塑性变化的能量学机理、调控网络和分子机制，进一步理解动物的生活史特征，及其应对环境变化的生存策略和适应机理。

在不同环境下小型哺乳动物体重和脂肪累积呈现“上调”和“下调”，暗示“调定点”的存在，这对其应对极端环境，提高生存机会具有重要意义。然而该“调定点”的模式、影响因素和能量学机制尚不清楚。本项目以黑线仓鼠为研究对象，测定了连续梯度低温-复温、暖温、高脂食物、限食/禁食，以及捕食风险对体重、脂肪累积、摄食量、代谢率，以及下丘脑神经肽表达等的影响，分析了“上、下调定点”白色脂肪组织差异表达基因和相关的脂代谢通路。结果发现1）随环境温度降低，黑线仓鼠代谢产热显著增强，体脂含量显著降低，接近下临界点水平，恢复至室温后脂肪累积显著增加，接近上临界点。2）暖温下饲喂高脂食物的黑线仓鼠，代谢产热显著降低，但脂肪累积显著增加，达到上临界点。3）限食和禁食使黑线仓鼠体重显著降低，身体脂肪动员增加，下丘脑NPY表达上调， POMC、CART、ObRb基因表达显著下调，血清瘦素水平和脂肪含量显著降低，达到下临界点，重喂食高脂食物后体重和脂肪累积反弹，达到上临界点。4）捕食风险使静息代谢率（RMR）增加了24.5%。脂肪重量降低了30.1%，血清瘦素水平显著降低、血清皮质醇水平显著升高。5)限食使脂肪组织403个基因表达显著上调，309个基因表达下调。捕食风险使216个基因表达显著上调，34个基因表达下调。在差异表达基因中，涉及11条脂代谢通路。研究结果表明，代谢产热的能量支出在诱导脂肪水平在“上、下临界点”波动过程中发挥关键作用，瘦素抵抗可能是脂肪累积的主要原因，是诱导上临界点的内在机制。黑线仓鼠通过增强脂肪酸的β氧化，促进脂肪酸降解，以应对食物资源短缺的环境，是诱导下临界点的重要脂质代谢机制之一。捕食风险促进甘油酯代谢，增强甘油分解代谢以促进能量释放及转化，从而为动物应对捕食风险应激提供能量，这可能是动物应对捕食风险、提高生存几率的重要能量学策略和脂质代谢机制。