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: 10621893
• 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/10621893
• 关键词: Acceleration; 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; 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; 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; pharmacologic; 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.

标题：米色脂肪细胞维持的调节及其对代谢结果的影响 项目总结/摘要 一个潜在的治疗目标，以遏制全球肥胖和糖尿病的流行是产热米色脂肪内 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中的产热脂肪细胞强烈消耗脂质和葡萄糖。然而，米色脂肪细胞很快 一旦刺激消失，年龄和肥胖会进一步加速这一过程。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。一个长期目标 我的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的初步研究中，我们证明了米色脂肪细胞可以被 通过药理学和遗传学手段诱导和维持。此外，我们的初步结果表明， 即使没有持续刺激，这些诱导的米色脂肪细胞也能在老年小鼠中维持。 这些令人兴奋的发现，虽然在性质上是初步的，但提出了使用米色脂肪细胞作为 治疗肥胖症、糖尿病和其它代谢疾病的潜在治疗剂。在这个应用程序中，我们将 研究持续的米色脂肪细胞是否可以改善健康和 疾病状况，从而达到抗肥胖和抗糖尿病的效果。此外，我们将阐明 米色脂肪细胞身份得以保留的关键分子机制。此外，我们将采用细胞- 类型选择性转录组学方法，以全面表征参与的分子组分 米色脂肪细胞维持。