Regulation of Adipose-Lymphatic Cross-talk

脂肪淋巴串扰的调节

基本信息

批准号：
10451587
负责人：
Evan D Rosen
金额：
$ 48.13万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-15 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10451587
关键词：
Adipocytes Adipose tissue Affect Back Biology Blood Blood Circulation Blood Vessels Brain Brown Fat Cells Complex Data Defect Energy Metabolism Enzymes Fatty acid glycerol esters Genes Genetic Models Glucose Goals Health Homeostasis Human Immune Inflammation Intercellular Fluid Knock-out Lead Lipids Lymphatic Lymphatic Endothelial Cells Lymphatic System Lymphatic function Mediating Metabolic Metabolic Diseases Metabolic dysfunction Metabolism Molecular Mus Neuropeptides Neurotensin Neurotensin Receptors Norepinephrine Nutrient Obesity Pathway interactions Peptides Peripheral Phenotype Physiological Physiology Process Production Regulation Rodent Role Series Signal Transduction Structure Sympathetic Nervous System Techniques Temperature Testing Text Thermogenesis adipocyte biology blood glucose regulation cell type cold temperature effective therapy energy balance hormonal signals improved in vitro Model in vivo insight knock-down lymph flow lymphatic development lymphatic dysfunction lymphatic vasculature lymphatic vessel metabolic abnormality assessment novel obesity treatment paracrine peptide hormone proneurotensin receptor single-cell RNA sequencing small molecule inhibitor solute

项目摘要

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.

抽象的脂肪组织是复杂且异型的，包含许多结构和细胞类型除了脂肪细胞。这包括淋巴血管，这些血管返回间质液，溶质和免疫细胞回到循环。有一个有据可查但无法解释的双向脂肪细胞与淋巴管之间的关系，使淋巴功能不良导致增加肥胖。相反，肥胖会导致淋巴流量受损。分子这些相互作用的基础是未知的。我们的单细胞RNA测序数据来自小鼠和人脂肪组织表明淋巴内皮细胞表达神经肽神经素（NTS）。我们表明NTS是一种有效的抗热剂，其表达是被寒冷的温度抑制。在这里，我们将表征调节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在淋巴管中失去NT或在脂肪细胞上的受体。这些研究将有助于解释脂肪与淋巴系统之间的困惑关系，也将带来新的见解控制神经肽对脂肪生理和代谢。