State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14687-92. doi: 10.1073/pnas.1212879109. Epub 2012 Aug 21.
Developmental arrest, a critical component of the life cycle in animals as diverse as nematodes (dauer state), insects (diapause), and vertebrates (hibernation), results in dramatic depression of the metabolic rate and a profound extension in longevity. Although many details of the hormonal systems controlling developmental arrest are well-known, we know little about the interactions between metabolic events and the hormones controlling the arrested state. Here, we show that diapause is regulated by an interplay between blood-borne metabolites and regulatory centers within the brain. Gene expression in the fat body, the insect equivalent of the liver, is strongly suppressed during diapause, resulting in low levels of tricarboxylic acid (TCA) intermediates circulating within the blood, and at diapause termination, the fat body becomes activated, releasing an abundance of TCA intermediates that act on the brain to stimulate synthesis of regulatory peptides that prompt production of the insect growth hormone ecdysone. This model is supported by our success in breaking diapause by injecting a mixture of TCA intermediates and upstream metabolites. The results underscore the importance of cross-talk between the brain and fat body as a regulator of diapause and suggest that the TCA cycle may be a checkpoint for regulating different forms of animal dormancy.
发育阻滞是动物生命周期中的一个关键组成部分，存在于线虫（ dauer 状态）、昆虫（休眠）和脊椎动物（冬眠）等多种生物中，其结果是代谢率显著降低，寿命显著延长。尽管控制发育阻滞的激素系统的许多细节已经众所周知，但我们对代谢事件与控制阻滞状态的激素之间的相互作用知之甚少。在这里，我们表明休眠是由血液传播的代谢物和大脑内的调节中心之间的相互作用调节的。在休眠期间，脂肪体（昆虫肝脏的对应物）中的基因表达受到强烈抑制，导致血液中三羧酸 (TCA) 中间产物水平降低，在休眠结束时，脂肪体被激活，释放大量 TCA 中间产物，作用于大脑，刺激调节肽的合成，促使昆虫生长激素蜕皮激素的产生。我们通过注射 TCA 中间产物和上游代谢物的混合物来打破休眠，这一结果支持了这一模型。这些结果强调了大脑和脂肪体之间相互作用作为休眠调节剂的重要性，并表明 TCA 循环可能是调节不同形式动物休眠的一个检查点。
