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Interleukin-13 in Central Regulation of Metabolism

Interleukin-13 在代谢中枢调节中的作用

基本信息

批准号：
10669632
负责人：
Mayer Marc Chalom
金额：
$ 4.33万
依托单位：
TUFTS UNIVERSITY BOSTON
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：
2021-08-16 至 2026-08-15
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10669632
关键词：
Adipocytes Adipose tissue Affect Biogenesis Body mass index Brain Brain region Cell Nucleus Cells Cues Cytokine Signaling Data Dopamine Eating Energy Metabolism Enzymes Exhibits Fasting Fatty acid glycerol esters Food Energy Gene Deletion Gene Expression Genetic Models Genetic study Glucose Intolerance Helper-Inducer T-Lymphocyte Hemorrhage Homeostasis Hormones Human Hyperphagia Hypothalamic structure IL13RA1 gene Immune Immune signaling Immune system Immunity Infiltration Inflammation Mediators Inflammatory Insulin Resistance Interleukin-1 beta Interleukin-13 Interleukin-4 Knock-out Knowledge LacZ Genes Lead Leptin Lesion Link Liver Lymphoid Macrophage Mediating Membrane Metabolic Metabolic dysfunction Metabolism Midbrain structure Modeling Molecular Mus Muscle NFKB Signaling Pathway Nervous System Neurons Non-Insulin-Dependent Diabetes Mellitus Nutritional Obesity Organ Overnutrition Pathologic Pathway interactions Peripheral Pharmaceutical Preparations Phenotype Population Production Receptor Gene Regulation Reporting Role Signal Pathway Signal Transduction Signaling Protein Site Stains Substantia nigra structure TNF gene Testing Thermogenesis Tissues Tyrosine 3-Monooxygenase Ventral Tegmental Area Weight Gain blood glucose regulation combat cytokine diabetes management dopaminergic neuron energy balance food consumption gain of function genomic locus glucose metabolism insulin sensitivity loss of function metabolic phenotype novel pandemic disease receptor response

项目摘要

PROJECT SUMMARY The immune system is an important and dynamic regulator of metabolism. In peripheral tissues, over-nutrition and obesity lead to marked changes in immune cell population, causing associated shifts in signaling and tissue function. While type I immunity is associated with the release of pro-inflammatory cytokines and insulin resistance, type II immunity has been shown to promote beige fat biogenesis, glucose homeostasis, and energy balance. In the brain, activation of the pro-inflammatory NF-kB signaling pathway can lead to hyperphagia and metabolic dysfunction. Whether activation of type II immune signaling pathways can restore energy balance and protect against obesity has not yet been investigated. IL-13 is a Th2 cytokine that signals through its cellular receptor IL-13R1. Whole body deletion of Il13ra1 causes obesity and loss of blood glucose homeostasis. Il13ra1 is expressed in the subtantia nigra and ventral tegmental area of the brain. Preliminary data show that specific deletion of Il13ra1 from the dopaminergic midbrain at least partially reproduces the metabolic phenotypes of the whole-body knockout. The substantia nigra and ventral tegmental area are the primary producers of dopamine in the CNS. Numerous studies have related central dopamine activity to energy balance. In this study, we will test the hypothesis that central IL-13 signals through its receptor in the dopaminergic midbrain to maintain energy balance. We will investigate the cellular and molecular mechanisms by which it does so. We will use both gain-of-function and loss-of-function genetic models to test our hypothesis. Knowledge from this study is expected to fill major gaps in our understanding of how the immune system interacts with the nervous system to coordinate metabolic regulation, and also to identify novel pathways in the CNS that modulate energy balance.

项目总结