Regulation of Adipose-Lymphatic Cross-talk

脂肪淋巴串扰的调节

• 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
• 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

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 脂肪组织复杂且异质，包含多种结构和细胞类型 除了脂肪细胞。这包括淋巴管，其返回间质液、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 脂肪细胞和淋巴管之间的关系，导致淋巴功能差 增加肥胖。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 人类脂肪组织显示淋巴内皮细胞表达神经肽 神经降压素（NTS）。我们证明 NTS 是一种有效的抗生热剂，其表达量为 受到寒冷气温的抑制。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 淋巴管中的 NTS 或其脂肪细胞上的受体丢失。这些研究将有助于解释 脂肪与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生理和代谢。