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.

项目摘要 肥胖是一种影响美国40％以上的流行病，并导致高风险 糖尿病的发展。随着脂肪组织的扩展，几个细胞和分子 途径会改变导致脂肪细胞功能障碍和胰岛素抵抗。黑色的 美国人面临患心血管疾病和2型的更大风险 糖尿病与白人对应物相比；但是，这些机制尚不清楚。 我们的实验室表明，肥胖症和 用ET-1拮抗剂治疗肥胖小鼠的葡萄糖和脂质稳态。 ET-1型B受体的脂肪细胞特异性敲除可减轻肥胖的诱导 小鼠血脂异常和胰岛素抵抗。有趣的是，黑人美国人有更高 与美国白人相比，循环ET-1提出了潜在的机制和 改善黑人美国人代谢综合征的目标。这个行政 补充剂将支持Haley Murphy女士的职业发展，她的目标是 确定ET-1在中引起脂肪细胞功能障碍的细胞内途径 肥胖小鼠进行临床前实验。其次，她将建立通往临床的途径 通过对去识别的内脏脂肪进行单个核RNA测序的研究 组织样品确定脂肪组织细胞构成的差异 肥胖的黑人和白人美国人。