Regulation of Adipose-Lymphatic Cross-talk

摘要 脂肪组织结构复杂，细胞种类繁多 除了脂肪细胞。这包括淋巴管，其返回组织间液、溶质和 免疫细胞回到血液循环中有一个很好的记录，但无法解释的双向 脂肪细胞和淋巴管之间的关系，例如淋巴功能差导致 肥胖症增加。相反，肥胖导致淋巴流动受损。分子 这些相互作用的基础是未知的。我们从小鼠和小鼠中获得的单细胞RNA测序数据， 人脂肪组织显示淋巴管内皮细胞表达神经肽 神经降压素（NTS）。我们表明，NTS是一种有效的抗产热剂，其表达是 被寒冷的温度所抑制。在这里，我们将描述调节NTS的机制 表达和处理，我们将利用最先进的技术来记录效果 失去淋巴管中的NTS或脂肪细胞上的受体。这些研究将有助于解释 脂肪和淋巴系统之间令人费解的关系，也将导致新的见解 通过神经肽控制脂肪生理和代谢。

ABSTRACT Adipose tissue is complex and heterogenous, containing numerous structures and cell types besides adipocytes. This includes lymphatic vessels, which return interstitial fluid, solutes, and immune cells back to circulation. There is a well-documented but unexplained bidirectional relationship between adipocytes and lymphatic vessels, such that poor lymphatic function leads to increased adiposity. Conversely, obesity results in impaired lymphatic flow. The molecular basis for these interactions is unknown. Our single cell RNA sequencing data from mouse and human adipose tissue revealed that lymphatic endothelial cells express the neuropeptide neurotensin (NTS). We show that NTS is a potent anti-thermogenic agent, and its expression is suppressed by cold temperatures. Here we will characterize the mechanisms regulating NTS expression and processing, and we will utilize state of the art techniques to document the effects of losing NTS in lymphatic vessels or its receptor on adipocytes. These studies will help explain the puzzling relationship between fat and the lymphatic system, and will also lead to new insights into control of adipose physiology and metabolism by neuropeptides.