Molecular mechanisms linking energy metabolism and thermoregulation

对于变温动物来说，行为在体温调节中起着重要的作用，各种各样的动物都能感知环境温度并向热舒适区移动。虽然大多数变温动物不使用代谢产生的热量来调节体温，但我们发现果蝇的体温调节行为高度依赖于能量代谢水平;线粒体氧化磷酸化的增加诱导了对低温的偏好（Science 323：1740-1743，2009），而通过抑制胰岛素信号传导抑制能量代谢引起了寻温的体温调节行为。在鉴定参与能量稳态控制的分子的过程中，我们发现在脂肪体（相当于哺乳动物肝脏和脂肪组织的组织）中表达的δ-9脂肪酸去饱和酶（desat 1）在控制能量代谢以及体温调节行为中起关键作用。desat 1的表达缺陷抑制线粒体氧化磷酸化，导致身体大小和趋温表型显着减少。相反，诱导表达的δ-12脂肪酸去饱和酶（秀丽隐杆线虫脂肪-2），产生亚油酸引起的身体大小的增加和低温偏好。这些观察结果表明，脂质去饱和的变化协调调节线粒体能量代谢和体温调节行为。

For ectothermic animals, behavior plays a major role in thermoregulation; a wide variety of animals sense the environmental temperature and move towards to thermally comfortable zone. Although most ectothermic animals do not use metabolically produced heat to regulate body temperature, we found that thermoregulatory behavior of Drosophila is highly dependent on the level of energy metabolism; the increase in mitochondrial oxidative phosphorylation induced preference for the low temperature (Science 323:1740-1743, 2009), while the suppression of energy metabolism by inhibiting insulin signaling caused a warm-seeking thermoregulatory behavior. During the course of identifying molecules involved in the control of energy homeostasis, we found that delta-9 fatty acid desaturase (desat1) expressed in the fat body, a tissue equivalent to mammalian liver and adipose tissue, played a pivotal role in the control of energy metabolism as well as thermoregulatory behavior. Defective expression of desat1 suppressed mitochondrial oxidative phosphorylation, causing a significant decrease in body size and warm-seeking phenotype. In contrast, induced expression of delta-12 fatty acid desaturase (Caenorhabditis elegansFat-2) that produces linoleic acid caused the increase in body size and the low-temperature preference. These observations suggest that the changes in lipid desaturation coordinately regulate mitochondrial energy metabolism and thermoregulatory behavior.