The Coordination of Lipid Synthesis and Breakdown in Metabolism and Aging

项目名称：代谢和衰老中脂质合成和降解的协调 摘要/总结 脂质失衡是肥胖的特征，也是许多与年龄有关的疾病的特征， 人类的生殖疾病然而，脂质代谢、衰老和生殖之间的关系 仍然研究得很少。我们建议使用线虫C.来描述这种关系。在 特别是，我们建议研究脂质合成和分解之间的平衡如何影响 生物体的衰老速度和健康状况。 In C. elegans，消除生殖细胞延长寿命.除了生育能力丧失，生殖细胞的去除是一个 这是对脂质代谢的一个重大挑战，因为动物需要阻止脂肪沉积到鸡蛋中， 它的脂质分布。因此，无生殖系蠕虫提供了一个独特的平台，以了解脂质平衡是如何 在复杂的多细胞动物的细胞和组织中建立，这些动物面临着主要的生理学问题， 变化我们发现，脂肪的产生和降解似乎同时增加， 对蠕虫生殖细胞丧失的反应。我们最近证明，在无生殖系的成年人中， 转录因子NHR-49上调脂肪酸β-氧化和去饱和过程， 脂质分解和积聚。独立地，我们还发现，这两个，以及许多 其它参与脂质合成和降解的过程，在生殖细胞去除后升高， 保守的转录因子TcR-16和TcR-1。这些数据使我们假设， 脂质合成和分解的协调增强通过以下方式促进对生殖细胞损失的适应： 确保脂质体内平衡。我们建议通过使用分子遗传学，显微镜和 生物化学方法。从这些研究中获得的知识很可能揭示基本的见解 脂质代谢与生殖和衰老的关系。 这些研究与人类健康和疾病有关，因为它们涉及主要的公共卫生问题。 比如衰老和肥胖。通过这些实验所取得的发现可以导致 针对与年龄有关的疾病和代谢疾病的治疗干预。

Project Title: The coordination of lipid synthesis and degradation in metabolism and aging ABSTRACT/SUMMARY Lipid imbalances are characteristic of obesity and a feature of many age-related ailments and reproductive pathologies in humans. Yet, the relationship between lipid metabolism, aging and reproduction remains poorly studied. We propose to use the nematode C. elegans to characterize this relationship. In particular, we propose to investigate how the balance between lipid synthesis and breakdown influences an organism's rate of aging and health. In C. elegans, eliminating the germline extends lifespan. Besides fertility loss, germline removal is a major challenge to lipid metabolism because the animal needs to stop fat deposition into eggs and reorganize its lipid profile. Thus, germline-less worms provide a unique platform to understand how lipid balance is established in the cells and tissues of complex multicellular animals that are facing major physiological changes. We have discovered that fat production and degradation appear to be increased simultaneously in response to germline loss in worms. We recently demonstrated that in germline-less adults a conserved transcription factor, NHR-49, upregulate fatty-acid β-oxidation and desaturation- processes that contribute to lipid breakdown and build-up, respectively. Independently, we have also discovered that these two, and many other processes involved in lipid synthesis and degradation, are elevated in response to germline removal by the conserved transcription factors, DAF-16 and TCER-1. These data have led us to hypothesize that the coordinated enhancement of lipid synthesis and breakdown facilitates the adaptation to germline loss by ensuring lipid homeostasis. We propose to test this hypothesis by using molecular genetics, microscopy and biochemical approaches. The knowledge obtained from these studies is likely to reveal fundamental insights into the relationship of lipid metabolism, reproduction and aging. These studies are of relevance to human health and disease because they address major public health issues such as aging and obesity. The discoveries made through these experiments can lead to the discovery of therapeutic interventions targeting age-related ailments and metabolic diseases.