Regulation of Adipose-Lymphatic Cross-talk

摘要 脂肪组织是复杂和异质的，包含许多结构和细胞类型 除了脂肪细胞。这包括淋巴管，它返回间质液体、溶质和 免疫细胞恢复循环。有一种有据可查但无法解释的双向 脂肪细胞与淋巴管的关系，导致淋巴功能低下 导致肥胖症增加。相反，肥胖会导致淋巴流动受损。分子 这些相互作用的基础尚不清楚。我们的单细胞RNA测序数据来自小鼠和 人体脂肪组织发现淋巴管内皮细胞表达神经肽 神经降压素(NTS)。我们发现NTS是一种有效的抗生热剂，它的表达是 被寒冷的温度所抑制。在这里，我们将描述调控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 淋巴管或脂肪细胞上NTS受体的缺失。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，也将带来新的见解 通过神经肽控制脂肪的生理和代谢。

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.