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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的棕色脂肪组织/BAT 中解偶联蛋白 1/Ucp1 介导的适应性产热对于体温调节和能量平衡。增加人类棕色脂肪的适应性生热作用被认为是增加能量消耗并最终改善代谢健康的替代策略，因为棕色脂肪的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种独特的现象，棕色脂肪细胞特异性 Lrpprc 敲除小鼠可以权衡 BAT 中线粒体驱动的 Ucp1 依赖性生热作用与全身代谢适应性。这提案将使用这种新的小鼠模型来研究 Ucp1 独立功能。目标 1 将调查棕色脂肪细胞中 ATF4 驱动的生热作用的潜在机制。目标 2 将确定这一过程的生理调节。目标 3 将解决其代谢对全身代谢的贡献。总的来说，该提案将揭示棕色（和/或米色）脂肪细胞超越 Ucp1 依赖性的新功能生热作用。