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| 线粒体膜脂参与长爪沙鼠(Meriones unguiculatus)能量代谢调节机制的研究 | |
| 其他题名 | Mitochondrial membrane remodeling during thermoregulation of Mongolian gerbils (Meriones unguiculatus) |
| 潘茜 | |
| 出版年 | 2014 |
| 学位类型 | 博士 |
| 导师 | 王德华 |
| 学位授予单位 | 中国科学院大学 |
| 中文摘要 | 环境温度固有的波动一直是对动物进行自然选择的重要进化压力之一。广泛分布于我国北部荒漠与半荒漠草原的长爪沙鼠(Meriones unguiculatus)长期面临剧烈的昼夜温度波动和季节性温度波动，具有较强的生理可塑性，主要表现为具有较宽的热中性区且在体重等表型特征对季节性温度变化、尤其是夏季高温的不敏感，是研究短期温度变化和长期温度驯化的优良动物模型。线粒体是动物消耗氧气、产生ATP的唯一场所，线粒体膜脂成分的变化响应快、耗能小，直接影响膜脂蛋白活性以及膜的质子漏通透性，是变温动物和冬眠动物能量代谢的重要调节方式之一，但在非冬眠内温动物中尚未有针对性研究。本论文假设线粒体膜脂重塑是长爪沙鼠能量调节的重要方式，实验在对长爪沙鼠能量代谢特征进行全面分析后，结合各项能量学生理和生化指标，采用脂质组学分析方法，对长爪沙鼠线粒体膜脂在能量代谢调节过程中的作用进行了探索，获得的主要结果和结论如下： 1、为了确定室内饲养长爪沙鼠的生理可塑性，实验用新型开放式代谢仪对长爪沙鼠的热中性区（TNZ）、基础代谢率（BMR）、非颤抖性产热（NST）和最大代谢率（MMR）进行了精确测定。结果表明，长爪沙鼠的TNZ为（26.5~28.9℃），BMR为87.0±8.0 mlO2/h，NST为350.4±12.5 mlO2/h，MMR为497.5±22.5 mlO2/h。实验证实室内饲养长爪沙鼠确实具有较宽的热中性区和很高的热中性区上限，这一热中性区上限是目前已有热中性区记录哺乳动物的最高值。长爪沙鼠在高体温下仍可保持较低代谢率，具有较强代谢调节能力，该物种可能存在独特的能量代谢调节机制。 2、为了研究线粒体膜脂参与长爪沙鼠短期能量代谢调节的机制。实验比较了热中性区以内38℃和27℃之间、热中性区以下27℃和16℃之间长爪沙鼠的各项能量学指标和线粒体膜脂的脂质组学成分变化。与热中性区下限附近温度(27℃)短期处理相比，实验表明38℃和16℃温度处理都可以使动物出现显著的线粒体膜脂重塑，线粒体膜脂质组学成分变化明显与短期能量代谢调节有关，可能在热中性区上限抑制了长爪沙鼠的代谢，在热中性区以下迅速提高了沙鼠的产热能力。其余生理指标无显著能量代谢调节相关变化。结果表明线粒体膜脂在长爪沙鼠短期温度变化中对调节细胞功能、维持产热与散热的平衡可能起到了重要作用。 3、为了研究线粒体膜脂在夏季高温驯化长爪沙鼠能量代谢调节机制中的作用。我们比较了30℃两个月高温驯化长爪沙鼠与对照组（23℃）之间包括线粒体膜脂成分在内的各项能量代谢生理差异。结果表明高温驯化使长爪沙鼠的基础代谢率降低、但适应性产热没变，更多的活性甲状腺素被转化成了稳定的甲状腺素储备，以线粒体膜脂重塑作为重要的能量代谢调节方式。这些都使长爪沙鼠在高温驯化中保留了适应昼夜温差和季节性温度变化的调节能力。沙鼠在高温下BAT体积的增加和BAT线粒体偶联呼吸活性的增强，可能在维持颤抖性产热的前提下增加了BAT组织的散热面积，提高了BAT线粒体的呼吸效率。这些特点可能都是长爪沙鼠适应我国北温带夏季剧烈的昼夜温度波动和强烈的季节性波动的主要原因，暗示了长爪沙鼠地理分布相对较广的生理原因。 总之，我们的结果进一步阐明了我们的研究首次探索了膜脂重塑在非冬眠内温动物中的能量代谢调节作用，线粒体膜脂参与下长爪沙鼠的能量代谢调节机制暗示了膜脂调节机制在大多数哺乳动物甚至人类应对温度波动，尤其是短期温度波动中的潜在作用。 |
| 英文摘要 | The inherent variability in climate represents one of the greatest selection pressures during animal evolution. Widely distributed in desert and semi-desert areas in the north of China, Monglian gerbils (Meriones unguiculatus) have been adapted to the large seasonal and daily temperature fluctuations in their habitat and have great physiological flexibility. This rodent have a very wide thermoneutral zone and is phenotypically insensitive to seasonal temperature changes, especially to the high temperature in summer, therefore, is a good animal modern to study animal thermoregulation during other short-term temperature changes and long term temperature acclimation. Mitochondria are the only site that oxygen is consumed for energy production. Mitochondrial membrane remodeling is considered fast and relatively inexpensive, and can interact directly with respiration related membrane protein, which leads to adjustment on protein activity and membrane proton leak. Numerous studies have found that mitochondrial membrane remodeling plays an important role in thermoregulation in ectotherms and hibernator, but such mechanism has never been explored in non-hibernating endotherms. This thesis hypothesizes that mitochondrial membrane remodeling may also participate importantly in thermoregulation of Mongolian gerbils. Novel lipidomic technique was introduced into my study to examine the detailed changes in membrane phospholipids during thermoregulation. Other energetic parameters were also measured for a fully observation during thermoregulation of gerbils. The main results and conclusions of this thesis are as follows: 1. In order to confirm the physiological flexibility of indoor bred Mongolian gerbils used in my study, open-circuit respirometer was used to measure gerbils’ thermoneutral zone (TNZ), basal metabolic rate (BMR), non-shivering thermogenisis (NST) and maximum metabolic rate (MMR). The results showed that the gerbils I used for my thesis has a TNZ ranges from 26.5oC to 38.9oC. Their BMR was 87.0±8.0 mlO2/h, NST was 350.4±12.5 mlO2/h, MMR was 497.5±22.5. This result was consistent with precious observations where gerbils had a wide TNZ and very high upper critical temperature, and confirmed the physiological flexibility we were going to study on. It is indicated in our result that gerbils might posses a good ability of thermoregulation, for they can maintain their metabolic rate in the basal level even when body temperatures were elevated significantly. 2. In order to study the role of mitochondrial membrane remodeling during acute thermoregulation of gerbils, I examined changes in the membrane phospholipids environment and free fatty acids (FFA) production in mitochondria between 38oC and 27oC (in the TNZ), and between 27oC and 16oC (below the TNZ). At 38oC, acute heat stress elicited distinct remodeling in mitochondrial membrane lipidome which related to a potential decrease in mitochondrial respiration and membrane fluidity compared to 27oC. At 16oC, a sharply decreased unsaturation index and increased chain lengths were detected in mitochondrial FFA production both in muscle and BAT. Our results suggest that mitochondrial membrane lipid remodeling may stabilize membrane function and activity of respiration related membrane protein to maintain a stable metabolic rate at upper critical temperature, and improve heat production under acute cold exposure. These data therefore imply an important role of membrane remodeling during acute thermoregulation in a non-hibernating endotherm. 3. In order to study the role of mitochondrial membrane remodeling during warm acclimation of Mongolian gerbils. Gerbils were acclimated to 30oC for two months. Compared to the control group, warm acclimated gerbils demonstrated lower BMRs but unchanged adaptive thermogenisis. Biological active thyroid hormone was transformed temporarily into inactive state. Mitochondrial membrane remodeling was the major change related to thermoregulation in |
| 中文关键词 | 长爪沙鼠 ; 线粒体 ; 膜脂 ; 能量代谢调节 ; 脂质组学 |
| 英文关键词 | Mongolian gerbils mitochondria membrane lipid thermoregulation lipidomics |
| 语种 | 中文 |
| 国家 | 中国 |
| 来源学科分类 | 生态学 |
| 来源机构 | 中国科学院动物研究所 |
| 资源类型 | 学位论文 |
| 条目标识符 | http://119.78.100.177/qdio/handle/2XILL650/287374 |
| 推荐引用方式 GB/T 7714 | 潘茜. 线粒体膜脂参与长爪沙鼠(Meriones unguiculatus)能量代谢调节机制的研究[D]. 中国科学院大学,2014. |
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