Endothelin-1 in Obesity and Insulin Resistance

内皮素 1 在肥胖和胰岛素抵抗中的作用

• 批准号: 10799222
• 负责人: Joshua S Speed
• 金额: $ 6.03万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-09 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10799222
• 关键词: Adipocytes; Adipose tissue; Administrative Supplement; Affect; Attenuated; Black American; Cardiovascular Diseases; Cells; Clinical Research; Data; Development; Diabetes Mellitus; Dyslipidemias; Endothelin-1; Epidemic; Fatty acid glycerol esters; Functional disorder; Glucose; Homeostasis; Insulin Resistance; Knock-out; Lipids; Metabolic syndrome; Molecular; Mus; Non-Insulin-Dependent Diabetes Mellitus; Nuclear RNA; Obese Mice; Obesity; Pathway interactions; Peptides; Population; Risk; Risk Factors; Tissue Expansion; Tissue Sample; Tissues; United States; Visceral; antagonist; career development; caucasian American; experimental study; high risk; improved; obese patients; pre-clinical; receptor; transcriptome sequencing

Project Summary Obesity is an epidemic that affects over 40% of the United States and leads to a high risk of development of diabetes. As adipose tissue expands, several cellular and molecular pathways are altered leading to adipocyte dysfunction and insulin resistance. Black Americans are at an even greater risk of developing cardiovascular disease and type 2 diabetes compared to white counterparts; however, the mechanisms are not understood. Our lab has shown that the peptide endothelin-1 (ET-1) is elevated in obesity and treatment with ET-1 antagonists improve glucose and lipid homeostasis in obese mice. Adipocyte specific knockout of the ET-1 type B receptor attenuates obesity induced dyslipidemia and insulin resistance in mice. Interestingly, black Americans have higher circulating ET-1 compared to white Americans suggesting a potential mechanism and target to improve metabolic syndrome in black Americans. This administrative supplement will support the career development of Ms. Haley Murphy as she aims to determine the intracellular pathways by which ET-1 causes adipocyte dysfunction in obese mice in pre-clinical experiments. Second, she will establish a pathway to clinical research by performing single nuclear RNA sequencing on de-identified visceral adipose tissue samples to determine differences in the cellular makeup of adipose tissue from obese black and white Americans.

项目概要 肥胖是一种流行病，影响了美国 40% 以上的地区，并导致高风险 糖尿病的发展。随着脂肪组织的扩张，一些细胞和分子 途径改变导致脂肪细胞功能障碍和胰岛素抵抗。黑色的 美国人患心血管疾病和 2 型疾病的风险更大 与白人相比患有糖尿病；然而，其机制尚不清楚。 我们的实验室表明，肽内皮素-1 (ET-1) 在肥胖和肥胖人群中升高。 ET-1 拮抗剂治疗可改善肥胖小鼠的葡萄糖和脂质稳态。 脂肪细胞特异性敲除 ET-1 B 型受体可减轻肥胖引起的症状 小鼠血脂异常和胰岛素抵抗。有趣的是，美国黑人拥有更高的 循环 ET-1 与美国白人的比较表明了潜在的机制 目标是改善美国黑人的代谢综合症。本次行政 补充品将支持 Haley Murphy 女士的职业发展，因为她的目标是 确定 ET-1 导致脂肪细胞功能障碍的细胞内途径 临床前实验中的肥胖小鼠。其次，她将建立一条临床途径 对未鉴定的内脏脂肪进行单核 RNA 测序的研究 组织样本以确定脂肪组织细胞组成的差异 肥胖的美国黑人和白人。