Function and regulation of Letmd1 in metabolic signaling

Letmd1在代谢信号中的功能和调节

• 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
• 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

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.

修改项目摘要/摘要部分 这个短期奖项是为了支持收集初步数据，以提交一项传统的研究资助，重点是Letmd 1在代谢调节中的作用。 产热棕色脂肪组织（BAT）与人类的心脏代谢健康有关。 重要的是要了解BAT产热是如何控制的，因为增强BAT产热可能会导致新的治疗干预措施，带来切实的健康益处。 我们最近证明，Letmd 1是选择性富集BAT和全球Letmd 1敲除（KO）小鼠表现出严重损害冷诱导产热。 在目标1中，我们将使用整体KO小鼠组织进行呼吸测定，以确定对OXPHOS呼吸的影响。在目标2中，我们将确定Letmd 1的表达是否在小鼠减肥手术模型中改变。 在目标3中，我们将测试是否可以检测到Letmd 1蛋白磷酸化的变化。 在目标4中，我们将生成脂肪特异性Letmd 1 KO小鼠模型。 这些目标将为提交的传统研究资助申请建立可行性。

项目成果

CFTR regulates brown adipocyte thermogenesis via the cAMP/PKA signaling pathway.

• DOI: 10.1016/j.jcf.2022.08.012
• 发表时间: 2023-01
• 期刊: JOURNAL OF CYSTIC FIBROSIS
• 影响因子: 5.2
• 作者: Choi, Kyung-Mi;Cho, Sung-Hee;Kim, Jung Hak;Kim, Ae-Rhee Lilian;Kong, Xiangmudong;Yoon, John C.
• 通讯作者: Yoon, John C.