Gap Junction Dependent and Independent Roles of Connexin43 in Metabolic Tissues

Connexin43 在代谢组织中的间隙连接依赖性和独立作用

• 批准号: 10301010
• 负责人: Yi Zhu
• 金额: $ 23.93万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10301010
• 关键词: Academic Training; Acclimatization; Acute; Adipocytes; Adipose tissue; Affect; Binding; Biology; Blood Glucose; Cardiac Myocytes; Cell membrane; Cells; Cellular Metabolic Process; Connexin 43; Connexins; Coupling; Data; Dependovirus; Diabetes Mellitus; Dyes; Evolution; Exposure to; Fasting; Gap Junctions; Genes; Genetic Transcription; Glucagon; Goals; Hepatic; Hepatocyte; High Fat Diet; Hormones; International; Knowledge; Life; Liver; Mass Spectrum Analysis; Measures; Mediating; Medical center; Medicine; Mentors; Mentorship; Metabolic; Metabolic Diseases; Metabolic syndrome; Metabolism; Mitochondria; Mus; Neurons; Obesity; Organ; Organism; Output; Oxygen Consumption; Pathway interactions; Permeability; Pharmaceutical Preparations; Pharmacology; Physiology; Positioning Attribute; Proteins; Proteomics; Protons; Publishing; Regulation; Research; Research Personnel; Research Proposals; Respiration; Role; Signal Pathway; Signal Transduction; Societies; Subcellular Fractions; Testing; Texas; Tissues; Training; Transcript; Universities; adipocyte differentiation; blood glucose regulation; career; clinical development; combat; experimental study; feeding; fibroblast growth factor 21; gap junction channel; glucose tolerance; improved; in vivo; insight; luciferin; novel; novel therapeutics; obesity treatment; overexpression; response

Project Summary/Abstract This proposal outlines an integrated training and research plan for Dr. Yi Zhu to complete further academic training under the mentorship of Dr. Philipp E. Scherer and transition to an independent investigator specializing in the research field of Connexin43 (Cx43) biology in metabolic adaptation. The overall objective of the research proposal is to understand the multifaceted roles of Connexin43 in the regulation of hepatic FGF21 secretion during fasting as well as its role in adipose tissue “beiging” during cold exposure. Obesity and diabetes remain a great burden to our society, and current medicines for obesity and diabetes have fell short of achieving treatment goals. So it is important to discover novel pathways that can be leveraged in combating obesity and diabetes. Recently, I have identified that Cx43 channels are implicated in the propagation of sympathetic neuronal outputs from cold exposure in adipose tissue. Systemic Cx43 overexpression in several metabolic tissues improves glucose tolerance and elevates circulating FGF21 levels in mice, a hormone with pleiotropic metabolic actions and holds great potential to be developed into a medication. So I generated several new mouse lines to further study the crosstalk between Connexin43 and FGF21, focusing on metabolic consequences of Connexin43 in liver and adipose tissues in vivo: Aim 1 investigates the role of Connexin43 gap junction channel in glucagon-stimulated hepatic FGF21 secretion during fasting, and also explore the mechanism by which Connexin43 regulates FGF21 expression. Aim 2 follows up on a new observation that Connexin43 translocates into beige adipocyte mitochondria during cold exposure, and tests the hypothesis that mitochondrial translocated Cx43 mediates UCP1-independent uncoupling in beige adipocytes. These proposed studies will expand our knowledge on Connexin43 in liver and adipose tissue, and guide us in pharmacologically targeting Cx43 for metabolic diseases, at the channel, the hemichannel, or simply the transcription levels. Under the auspices of the University of Texas Southwestern Medical Center, I will be mentored by internationally recognized leaders in the metabolism field, which will aid the transition of my research career toward an independent investigator position.

项目概述/摘要本提案概述了一项针对Yi Zhu博士的综合培训和研究计划

项目成果

Maternal Adipocyte Connexin43 Gap Junctions Affect Breastmilk Lactose Levels and Neonate Growth in Mice.

• DOI: 10.3390/biology11071023
• 发表时间: 2022-07-07
• 期刊: BIOLOGY-BASEL
• 影响因子: 4.2
• 作者: Huang, Mingyang;Song, Anying;Chen, Xi;Ishtiaq, Sarah;Wang, Chunmei;Hadsell, Darryl L.;Wang, Qiong A.;Zhu, Yi
• 通讯作者: Zhu, Yi