Expression data from synchronized L4 C. elegans during starvation

The endoplasmic reticulum (ER) is an organelle associated with lipid metabolism. However, the involvement of the ER in nutritional status-dependent energy homeostasis is largely unknown. The results of this study demonstrate that IRE-1, an ER protein known to be involved in the unfolded protein response, and HSP-4, an ER chaperone, regulate expression of the novel fasting-induced lipases FIL-1 and FIL-2, which induce fat granule hydrolysis upon fasting in C. elegans. RNAi and ectopic expression experiments demostrated that FIL-1 and FIL-2 are both necessary and sufficient for fasting-induced fat granule breakdown. Failure of ire-1 and hsp-4 mutant animals to hydrolyze fat granules during starvation impaired their motility, which was rescued by glucose supplementation of their media, implicating the importance of ire-1/hsp-4-dependent lipolysis for energy supply from stored fat during fasting. Taken together, these data suggest that the ER-resident proteins IRE-1 and HSP-4 are key nutritional sensors that modulate expression of inducible lipases to maintain whole-body energy homeostasis in C. elegans.内质网（ER）是一类与脂质代谢相关的细胞器。然而，内质网在营养状态依赖性能量稳态中的参与机制仍未被完全阐明。本研究结果显示，参与未折叠蛋白反应（unfolded protein response）的内质网蛋白IRE-1，以及内质网分子伴侣HSP-4，可调控新型禁食诱导脂肪酶FIL-1与FIL-2的表达；这两种脂肪酶可在秀丽隐杆线虫（C. elegans）禁食状态下介导脂肪颗粒水解。RNA干扰（RNAi）与异位表达（ectopic expression）实验证实，FIL-1与FIL-2对于禁食诱导的脂肪颗粒分解既是必需的，也是充分的。ire-1与hsp-4基因突变体动物在饥饿状态下无法完成脂肪颗粒水解，这会损害其运动能力；向其培养基中添加葡萄糖可挽救该表型，这表明依赖ire-1/hsp-4的脂肪分解过程，对于禁食期间依靠储存脂肪供能具有关键意义。综上，上述数据表明，内质网驻留蛋白IRE-1与HSP-4是关键营养感受器，可通过调控诱导型脂肪酶的表达，维持秀丽隐杆线虫的全身能量稳态。