Regulation of beige adipocyte maintenance and its impact on metabolic outcomes

米色脂肪细胞维持的调节及其对代谢结果的影响

• 批准号: 10420996
• 负责人: Yuwei Jiang
• 金额: $ 51.92万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-15 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10420996
• 关键词: Adipocytes; Adipose tissue; Age; Aging; Autophagocytosis; Biological Markers; CDKN2A gene; Cell Cycle; Cells; Chronic; Consumption; Cyclin-Dependent Kinases; Data; Development; Diabetes Mellitus; Disease; Energy Metabolism; Epidemic; Excision; Fatty acid glycerol esters; Genetic; Genetic study; Glucose; Goals; Health; Insulin Resistance; Laboratories; Lipids; Longevity; Maintenance; Measures; Metabolic; Metabolic Diseases; Metabolic dysfunction; Molecular; Mus; Nature; Non obese; Obesity; Outcome; Pathologic; Pathway interactions; Pharmacology; Phenocopy; Phenotype; Physiological; Process; Proteins; Regulation; Role; Signal Transduction; Stimulus; System; TP53 gene; Testing; Therapeutic; Work; adipocyte biology; arm; cell type; combat; design; diet-induced obesity; experimental study; improved; in vivo; inhibitor; insight; insulin sensitivity; metabolic fitness; metabolic phenotype; mouse genetics; mouse model; new therapeutic target; novel; novel strategies; p19ARF; preservation; prevent; programs; recruit; response; senescence; therapeutic target; transcriptomics; uncoupling protein 1

Title: Regulation of beige adipocyte maintenance and its impact on metabolic outcomes Project Summary/Abstract A potential therapeutic target to curb the global obesity and diabetes epidemic is thermogenic beige fat within white adipose tissue (WAT). Unlike white adipocyte which stores fat, beige adipocytes are stimulated thermogenic fat cells in WAT that robustly consume lipid and glucose. However, Beige adipocytes quickly disappear upon the removal of stimuli, a process further accelerated by age and obesity. This creates a key challenge to explore beige adipocytes as a sustainable therapy for chronic metabolic diseases. A long-term goal of my laboratory is to understand the development and maintenance of beige adipocytes, and the metabolic outcomes. In our preliminary studies using unique mouse models, we demonstrate that beige adipocytes can be induced and maintained by pharmacological and genetical measures. Further, our preliminary results suggest that these induced beige adipocytes are maintained in the older mice, even without continuous stimulation. These exciting findings, although preliminary in nature, suggest novel measures to use beige adipocyte as potential therapeutics to treat obesity, diabetes, and other metabolic diseases. In this application, we will investigate whether the sustained beige adipocytes can improve the metabolic fitness under both health and disease conditions, thereby achieving anti-obesity and anti-diabetes effects. Furthermore, we will elucidate the critical molecular mechanisms by which beige adipocyte identity is preserved. In addition, we will employ cell- type selective transcriptomic approach to comprehensively characterize the molecular components involved in beige adipocyte maintenance.

米色脂肪细胞维持的调节及其对代谢结果的影响 项目摘要/摘要 抑制全球肥胖和糖尿病流行的一个潜在治疗目标是体内产热的米色脂肪 白色脂肪组织(Wat)。与储存脂肪的白色脂肪细胞不同，米色脂肪细胞受到刺激 Wat中大量消耗脂肪和葡萄糖的生热脂肪细胞。然而，米色脂肪细胞很快 在去除刺激后消失，这个过程因年龄和肥胖而进一步加速。这将创建一个密钥 探索米色脂肪细胞作为慢性代谢性疾病的可持续疗法的挑战。长期目标 我实验室的目的是了解米色脂肪细胞的发育和维持，以及代谢 结果。在我们使用独特的小鼠模型进行的初步研究中，我们证明了米色脂肪细胞可以 由药理学和遗传学措施诱导和维持的。此外，我们的初步结果表明 这些诱导的米色脂肪细胞在老年小鼠中保持不变，即使没有持续的刺激。 这些令人兴奋的发现，虽然在性质上是初步的，但提出了将米色脂肪细胞用作 治疗肥胖、糖尿病和其他代谢性疾病的潜在疗法。在此应用程序中，我们将 探讨持续米色脂肪细胞能否改善健康和健康状态下的代谢适合性 病情，从而达到抗肥胖和抗糖尿病的效果。此外，我们将澄清 米色脂肪细胞特性被保存的关键分子机制。此外，我们还将使用手机- 类型选择性转录法全面鉴定参与的分子组成 米色脂肪细胞保养。