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NNAT in metabolic regulation

NNAT 在代谢调节中的作用

基本信息

批准号：
10521829
负责人：
JOHN C YOON
金额：
$ 40.04万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10521829
关键词：
ATP Hydrolysis Adipocytes Adipose tissue Adrenergic Agents Adrenergic Receptor Affect Alanine Anti-Obesity Agents Area Back Binding Biological Assay Body Composition Body Weight Brown Fat Ca(2+)-Transporting ATPase Chemicals Consumption Creatine Data Desire for food Ectopic Expression Endoplasmic Reticulum Energy Metabolism Exhibits Extravasation Fatty acid glycerol esters Fluorescence Resonance Energy Transfer Future Genes Genetic Polymorphism Health Health Care Costs High Fat Diet Human Indirect Calorimetry Knock-out Knockout Mice Lead Link Lipids Lipolysis Measures Mediating Membrane Proteins Metabolic Modeling Monitor Mus Mutagenesis Obesity Parents Pharmacology Physiological Play Positron-Emission Tomography Process Proteins Pump Reagent Regulation Reporting Resistance Respiration Role Signal Transduction Site Stimulus Temperature Testing Therapeutic Thermogenesis Tissues United States Work base blood glucose regulation combat endoplasmic reticulum stress energy balance fluorodeoxyglucose gain of function improved in vivo inhibitor insight medical complication mouse model novel novel strategies novel therapeutic intervention obesity in children obesity treatment overexpression phospholamban response sarcolipin small molecule trafficking uncoupling protein 1 uptake warm temperature wasting

项目摘要

PROJECT SUMMARY/ABSTRACT Obesity is associated with serious medical complications and responsible for a rising percentage of health care costs in the United States. While most anti-obesity drugs in the market work by suppressing appetite, increasing energy expenditure by stimulating thermogenesis is an alternative strategy. Humans and mice both possess constitutively active and inducible thermogenic fat, commonly called brown and beige fat. While Uncoupling Protein 1 (UCP1) has long been considered essential for non-shivering thermogenesis in adipose tissues, recent studies have demonstrated UCP1-independent thermogenic mechanisms, and they may be especially important in beige fat. We recently identified the endoplasmic reticulum (ER) membrane protein Nnat as a novel inhibitor of adipocyte thermogenesis and have shown that its effects on thermogenesis are UCP1-independent. We hypothesize that Nnat in adipose tissue plays a key role in controlling thermogenesis and glucose homeostasis. In Aim 1, we will characterize the regulation of systemic energy metabolism by adipose tissue Nnat. In Aim 2, we will investigate the mechanistic basis of Nnat action and will examine its interactions with the ER calcium pump SERCA and other possible ways that Nnat can impact thermogenesis. These studies will produce new insights into the control of adipose tissue thermogenesis and potentially lead to new strategies for anti-obesity therapy.

项目总结/摘要肥胖与严重的医疗并发症有关，并导致医疗保健的比例上升在美国的成本。虽然市场上大多数减肥药都是通过抑制食欲来起作用的，通过刺激产热来增加能量消耗是一种替代策略。人类和老鼠具有组成性活性和诱导产热脂肪，通常称为棕色和米色脂肪。而解偶联蛋白1（UCP 1）长期以来被认为是脂肪组织非颤抖性产热的必需蛋白。组织，最近的研究表明，UCP 1独立的产热机制，他们可能是尤其是米色脂肪。我们最近发现了内质网（ER）膜蛋白 NNAT作为一种新的脂肪细胞产热抑制剂， UCP 1-独立。我们假设脂肪组织中的Nnat在控制产热中起关键作用和葡萄糖稳态。在目标1中，我们将通过以下方式描述全身能量代谢的调节：脂肪组织在目标2中，我们将研究Nnat作用的机制基础，并将研究其与ER钙泵SERCA的相互作用以及Nnat可以影响产热的其他可能方式。这些研究将对脂肪组织产热的控制产生新的见解，并可能导致抗肥胖治疗的新策略。