Function and regulation of Letmd1 in metabolic signaling

Letmd1在代谢信号中的功能和调节

基本信息

批准号：
10553356
负责人：
JOHN C YOON
金额：
$ 15.91万
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：
2022-05-19 至 2024-05-18
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10553356
关键词：
ATF2 gene Adipocytes Adipose tissue Adrenergic Agents Agonist Alanine Binding Proteins Biological Assay Body Composition Body Weight Brown Fat Cells Cellular Metabolic Process Clinical Research Coronary Arteriosclerosis Cues Cyclic AMP Cyclic AMP Response Element Cyclic AMP-Dependent Protein Kinases Cyclic AMP-Responsive DNA-Binding Protein Data Defect Development Diet Dyslipidemias Energy Metabolism Exhibits Fatty Acids Fatty acid glycerol esters Gene Expression Genes Genetic Transcription Health Heart Diseases High Fat Diet Human Hypothalamic structure Impairment Indirect Calorimetry Inner mitochondrial membrane Intervention Knock-out Knockout Mice Knowledge Lead Link Lipid Mobilization Liver LoxP-flanked allele Mass Spectrum Analysis Mediating Mediator of activation protein Metabolic Mitochondria Mitochondrial Proteins Modeling Monitor Morphology Mus Nature Non-Insulin-Dependent Diabetes Mellitus Obesity Operative Surgical Procedures Pharmacology Phenotype Phosphorylation Phosphorylation Site Phosphotransferases Physiological Positioning Attribute Positron-Emission Tomography Predisposition Process Proteins Proteomics Proton-Translocating ATPases Reagent Regulation Research Role Serine Signal Pathway Signal Transduction Site Stimulus Structure Temperature Testing Therapeutic Thermogenesis Tissues Work adiponectin bariatric surgery base blood glucose regulation cardiometabolism cell type cold stress combat diabetes risk diet-induced obesity energy balance fibroblast growth factor 21 fluorodeoxyglucose glucose disposal glucose metabolism glucose tolerance glucose uptake human subject improved in vivo insight insulin sensitivity insulin tolerance lipid metabolism loss of function mutant novel promoter recruit response subcutaneous transcription factor transcriptome uptake

项目摘要

Modified Project Summary/Abstract Section This short-term award is to support the collection of preliminary data for submission of a conventional research grant that focuses on the role of Letmd1 in metabolic regulation. Thermogenic brown adipose tissue (BAT) has been associated with cardiometabolic health in humans. It is important to understand how BAT thermogenesis is controlled because enhancing BAT thermogenesis could lead to new therapeutic interventions with tangible health benefits. We recently demonstrated that Letmd1 is selectively enriched in BAT and that global Letmd1 knockout (KO) mice exhibit severe impairment of cold-induced thermogenesis. In Aim 1, we will perform respirometry with global KO mouse tissues to determine the effect on OXPHOS respiration. In Aim 2, we will determine if the expression of Letmd1 is altered in a mouse bariatric surgery model. In Aim 3, we will test if changes in Letmd1 protein phosphorylation can be detected. In Aim 4, we will generate a fat-specific Letmd1 KO mouse model. These Aims will establish feasibility for the conventional research grant application to be submitted.

修改后的项目摘要/摘要部分该短期奖项旨在支持收集初步数据，以提交常规研究资助，重点关注 Letmd1 在代谢调节中的作用。产热棕色脂肪组织（BAT）与人类心脏代谢健康有关。了解如何控制 BAT 生热作用非常重要，因为增强 BAT 生热作用可能会带来具有切实健康益处的新治疗干预措施。我们最近证明，Letmd1 在 BAT 中选择性富集，并且全局 Letmd1 敲除 (KO) 小鼠表现出寒冷诱导的生热作用的严重受损。在目标 1 中，我们将使用全局 KO 小鼠组织进行呼吸测量，以确定对 OXPHOS 呼吸的影响。在目标 2 中，我们将确定 Letmd1 的表达在小鼠减肥手术模型中是否发生改变。在目标 3 中，我们将测试是否可以检测到 Letmd1 蛋白磷酸化的变化。在目标 4 中，我们将生成脂肪特异性 Letmd1 KO 小鼠模型。这些目标将为提交传统研究资助申请建立可行性。