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Molecular control of beige fat heterogeneity

米色脂肪异质性的分子控制

基本信息

批准号：
10645161
负责人：
Shingo Kajimura
金额：
$ 48.13万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-20 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10645161
关键词：
Acclimatization Adipocytes Adipose tissue Adrenergic Receptor Adult Agonist Biogenesis Biological Biological Process Brown Fat CD81 gene CRISPR interference Cell Differentiation process Cells Chronic Crista ampullaris Cues Data Development Exercise Fatty acid glycerol esters Fibrosis Genetic Genetic Transcription Glucose Glucose Intolerance Health Heterogeneity Homeostasis Hormonal Inflammation Insulin Resistance Intermittent fasting Label Lipids Mediator Metabolic Mitochondria Molecular Mus Nature Pathologic Pathway interactions Physiological Play Population Proteins RNA analysis Regulation Reporter Repression Research Role Signal Pathway Signal Transduction Stimulus Technology Testing Thermogenesis Tissues adipocyte differentiation angiogenesis autocrine barrier to testing improved in vivo insulin sensitivity lipid biosynthesis nerve supply oxidation paracrine progenitor recruit stem stem cell proliferation stem cells tissue injury tissue repair tool

项目摘要

PROJECT SUMMARY Emerging evidence illuminates the biological significance of beige fat, an inducible form of thermogenic fat cells, in the regulation of metabolic health. The best-known stimulus of beige fat biogenesis is cold acclimation and subsequent activation of the β3-adrenoceptor (β3-AR) signaling pathway; however, recent studies identified a variety of external stimuli, such as tissue injury and intermittent fasting, that stimulate beige fat biogenesis through β3-AR independent pathways. Furthermore, our recent study identified a previously uncharacterized population of beige fat, referred to as glycolytic beige adipocytes (or g-beige fat), whose developmental regulation and origin are distinct from β3-AR-induced beige fat. These results lead us to hypothesize that beige fat is composed of developmentally diverse cell populations, and that each population plays unique biological roles depending on the nature of external cues (e.g., cold vs. tissue injury). A technical hurdle to test the hypothesis, however, is the lack of genetic tools that enable us to target particular adipocyte progenitor populations. Thus, we employed single-cell RNA (scRNA) analysis and identified two distinct adipocyte progenitor cells (APCs) that give rise to cold-induced beige adipocytes (CD81+ APCs) and g-beige fat from a myogenic lineage (MyoD+ APCs). Accordingly, this proposal aims to test the above hypothesis by determining the developmental regulation, molecular mechanisms, and biological function of beige adipocytes stem from CD81+ APCs and MyoD+ APCs. Our contribution in this proposal is to provide a fundamental understanding as to how heterogeneous beige adipocyte populations are regulated by physiological and pathological cues, and how they contribute to the regulation of metabolic tissue homeostasis, such as fuel oxidation, angiogenesis, innervation, tissue fibrosis, and inflammation.

项目摘要新出现的证据阐明了米色脂肪的生物学意义，米色脂肪是产热脂肪细胞的一种诱导形式，代谢健康的调节。米色脂肪生物合成的最著名的刺激是冷驯化，随后激活β3-肾上腺素受体（β3-AR）信号通路;然而，最近的研究发现，各种外部刺激，如组织损伤和间歇性禁食，刺激米色脂肪生物合成通过β3-AR非依赖性途径。此外，我们最近的研究发现了一种以前没有特征的一群米色脂肪，称为糖酵解米色脂肪细胞（或g-米色脂肪），其发育调节和起源与β3-AR诱导的米色脂肪不同。这些结果使我们假设米色脂肪是由发育不同的细胞群组成的，每个种群根据外部线索的性质发挥独特的生物学作用（例如，冷与组织伤害）。然而，测试这一假设的一个技术障碍是缺乏使我们能够靶向特定的脂肪细胞祖细胞群。因此，我们采用单细胞RNA（scRNA）分析并鉴定了两种不同的脂肪细胞祖细胞（APC），产生冷诱导的米色脂肪细胞（CD 81 + APC），来自肌源性谱系的g-米色脂肪（MyoD+ APC）。因此，本提案旨在检验上述假设通过确定米色脂肪细胞的发育调节、分子机制和生物学功能，来源于CD 81 + APC和MyoD+ APC。我们在这一建议中的贡献是提供一个基本的了解异源米色脂肪细胞群是如何被生理和病理线索，以及它们如何有助于调节代谢组织稳态，如燃料氧化、血管生成、神经支配、组织纤维化和炎症。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection.

DOI：
10.1038/s41467-023-42918-8
发表时间：
2023-11-03
期刊：
NATURE COMMUNICATIONS
影响因子：
16.6
作者：
Sinton, Matthew C.;Chandrasegaran, Praveena R. G.;Capewell, Paul;Cooper, Anneli;Girard, Alex;Ogunsola, John;Perona-Wright, Georgia;Ngoyi, Dieudonne;Kuispond, Nono;Bucheton, Bruno;Camara, Mamadou;Kajimura, Shingo;Benezech, Cecile;Mabbott, Neil A.;Macleod, Annette;Quintana, Juan F.
通讯作者：
Quintana, Juan F.

A new way to ignite thermogenesis in human adipose tissue.

一种点燃人体脂肪组织生热作用的新方法。