Ucp1-independent functions in brown and beige adipocytes

棕色和米色脂肪细胞中独立于 Ucp1 的功能

• 批准号: 10532159
• 负责人: Biao Wang
• 金额: $ 57.71万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10532159
• 关键词: Abbreviations; Ablation; Acids; Acute; Adipocytes; Adipose tissue; Aging; Brown Fat; Cell Nucleus; Cells; Defect; Diet; Dietary Proteins; Diphtheria Toxin; Energy Metabolism; Etiology; Exhibits; Family; Future; Genetic; Health; High Fat Diet; Homeostasis; Human; In Vitro; Investigation; Knock-out; Knockout Mice; Leigh Disease; Leucine; Lipids; Mass Spectrum Analysis; Mediating; Metabolic; Metabolic Diseases; Metabolic dysfunction; Metabolism; Mitochondria; Mitochondrial DNA; Molecular; Mus; Mutation; Physiologic Thermoregulation; Physiological; Process; Protein-Restricted Diet; Proteins; Proteome; RNA; Receptor Signaling; Regulation; Respiration; Role; Side; Stress Tests; Temperature; Therapeutic; Thermogenesis; Variant; Visualization; Work; beta-adrenergic receptor; cold stress; complex IV; conditional knockout; cytochrome c oxidase; energy balance; feeding; improved; in vivo; metabolic fitness; mouse model; novel; novel therapeutic intervention; obesity treatment; overexpression; programs; response; uncoupling protein 1; uptake

ABSTRACT Uncoupling protein 1/Ucp1-mediated adaptive thermogenesis in brown adipose tissue/BAT is essential for thermoregulation and energy balance. Increasing adaptive thermogenesis in human brown fat has been considered as an alternative strategy to increase energy expenditure, and ultimately to improve metabolic health, since brown fat activity gradually declines with aging and metabolic diseases. Our previous work identified a unique phenomenon that brown adipocyte-specific Lrpprc knockout mice can trade off mitochondria-fueled Ucp1-dependent thermogenesis in BAT for systemic metabolic fitness. This proposal will use this new mouse model to investigate Ucp1-independent functions. Aim 1 will investigate the underlying mechanisms of the ATF4-driven thermogenesis in brown adipocytes. Aim 2 will determine the physiological regulation of this process. Aim 3 will address its metabolic contributions to systemic metabolism. Collectively, this proposal will reveal novel functions of brown (and/or beige) adipocytes beyond Ucp1-dependent thermogenesis.

摘要 解偶联蛋白1/Ucp 1介导的棕色脂肪组织适应性产热/BAT是 体温调节和能量平衡。增加人类棕色脂肪中的适应性产热已经被证明是一种有效的方法。 被认为是增加能量消耗并最终改善代谢健康的替代策略， 因为棕色脂肪活性随着衰老和代谢疾病而逐渐下降。 我们之前的工作发现了一个独特的现象，棕色脂肪细胞特异性Lrpprc敲除小鼠可以 在BAT中权衡以Ucp 1为燃料的Ucp 1依赖性产热作用，以获得系统代谢适应性。这 该提案将使用这种新的小鼠模型来研究Ucp 1独立功能。目标1将调查 棕色脂肪细胞中ATF 4驱动产热的潜在机制。目标2将决定 这一过程的生理调控。目标3将阐述其对全身代谢的代谢贡献。 总的来说，这个提议将揭示棕色（和/或米色）脂肪细胞除了Ucp 1依赖性外的新功能。 产热作用