Lipid droplets (LDs) serve as crucial hubs for lipid trafficking and metabolic regulation through their numerous interactions with various organelles. While the interplay between LDs and the Golgi apparatus has been recognized, their roles and underlying mechanisms remain poorly understood. Here, we reveal the role of Ras-related protein Rab-2A (Rab2A) in mediating LD-Golgi interactions, thereby contributing to very-low-density lipoprotein (VLDL) lipidation and secretion in hepatocytes. Mechanistically, our findings identify a selective interaction between Golgi-localized Rab2A and 17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13) protein residing on LDs. This complex facilitates dynamic organelle communication between the Golgi apparatus and LDs, thus contributing to lipid transfer from LDs to the Golgi apparatus for VLDL2 lipidation and secretion. Attenuation of Rab2A activity via AMP-activated protein kinase (AMPK) suppresses the Rab2A-HSD17B13 complex formation, impairing LD-Golgi interactions and subsequent VLDL secretion. Furthermore, genetic inhibition of Rab2A and HSD17B13 in the liver reduces the serum triglyceride and cholesterol levels. Collectively, this study provides a new perspective on the interactions between the Golgi apparatus and LDs.

中文翻译：

---

Rab2A 介导的高尔基体-脂滴相互作用支持肝细胞中极低密度的脂蛋白分泌。


脂滴 （LDs） 通过与各种细胞器的多次相互作用，成为脂质运输和代谢调节的重要枢纽。虽然 LDs 和高尔基体之间的相互作用已经得到认可，但它们的作用和潜在机制仍然知之甚少。在这里，我们揭示了 Ras 相关蛋白 Rab-2A （Rab2A） 在介导 LD-高尔基体相互作用中的作用，从而有助于肝细胞中极低密度脂蛋白 （VLDL） 的脂质化和分泌。从机制上讲，我们的研究结果确定了高尔基体定位的 Rab2A 与驻留在 LD 上的 17-β-羟基类固醇脱氢酶 13 （HSD17B13） 蛋白之间的选择性相互作用。这种复合物促进高尔基体和 LD 之间的动态细胞器通讯，从而有助于脂质从 LD 转移到高尔基体以进行 VLDL2 脂质化和分泌。通过 AMP 活化蛋白激酶 （AMPK） 减弱 Rab2A 活性会抑制 Rab2A-HSD17B13 复合物的形成，从而损害 LD-高尔基体相互作用和随后的 VLDL 分泌。此外，肝脏中 Rab2A 和 HSD17B13 的遗传抑制可降低血清甘油三酯和胆固醇水平。总的来说，本研究为高尔基体和 LDs 之间的相互作用提供了新的视角。