Division of Science, Pennsylvania State University, Berks Campus, Reading, PA 19610, USA.
Med Sci (Basel). 2022 Dec 26;11(1):5. doi: 10.3390/medsci11010005.
Defects in how excess nutrients are stored as triglycerides can result in several diseases including obesity, heart disease, and diabetes. Understanding the genes responsible for normal lipid homeostasis will help understand the pathogenesis of these diseases. RNAi screens performed in cells identified genes involved in vesicle formation and protein sorting as important for the formation of lipid droplets; however, all of the vesicular trafficking proteins that regulate lipid storage are unknown. Here, we characterize the function of the Charged multivesicular protein 1 () gene in regulating fat storage. is a member of the ESCRT-III complex that targets membrane localized signaling receptors to intralumenal vesicles in the multivesicular body of the endosome and then ultimately to the lysosome for degradation. When levels are decreased specifically in the fly fat body, triglyceride accumulates while fat-body-specific overexpression decreases triglycerides. controls triglyceride storage by regulating the number and size of fat body cells produced and not by altering food consumption or lipid metabolic enzyme gene expression. Together, these data uncover a novel function for in controlling lipid storage in and supports the role of the endomembrane system in regulating metabolic homeostasis.
过量营养物质作为甘油三酯储存方式的缺陷可导致多种疾病，包括肥胖、心脏病和糖尿病。了解正常脂质稳态相关的基因有助于理解这些疾病的发病机制。在 细胞中进行的 RNAi 筛选鉴定了参与囊泡形成和蛋白质分拣的基因，这些基因对脂滴的形成很重要；然而，调节脂质储存的所有囊泡运输蛋白尚不清楚。在这里，我们研究了 Charged multivesicular protein 1 ( )基因在调节脂肪储存中的功能。 是 ESCRT-III 复合物的成员，可将膜定位的信号受体靶向到内涵体多泡体的腔内小泡中，然后最终靶向到溶酶体进行降解。当 蛋白在果蝇脂肪体中的水平特异性降低时，甘油三酯会积累，而脂肪体特异性过表达 则会降低甘油三酯。 通过调节脂肪体细胞的数量和大小来控制甘油三酯的储存，而不是通过改变食物消耗或脂质代谢酶基因的表达。总之，这些数据揭示了 在控制 中脂质储存的新功能，并支持了内膜系统在调节代谢稳态中的作用。
