Molecular responses and physiological implications to systemic stimuli in adipocyte progenitor cells

脂肪组织对新陈代谢和一般健康有重要影响。现在公认的是，脂肪不像人们曾经认为的那样，是一种被动的能量储存组织，它是一种动态组织，对不断变化的生理需求和全身信号做出反应，并分泌各种具有新陈代谢影响的强大激素。脂肪组织中的主要细胞类型是脂肪细胞，最近的研究表明，脂肪细胞的类型存在异质性，包括不同的功能特性。用细胞能量学对脂肪细胞进行分类可以分为两大类：储存能量的脂肪细胞(白色脂肪细胞)和分散能量的脂肪细胞(棕色脂肪细胞)。也许最有趣的是，在一个脂肪储存库中可以存在不止一种类型的脂肪细胞；特别是在啮齿类动物的皮下脂肪储存库中，主要是白色的，也有一些脂肪细胞具有棕色脂肪细胞的特性，被称为白褐色脂肪细胞或米色脂肪细胞。此外，这些脂肪细胞的数量是动态的，对系统信号和环境的变化做出反应。随着肥胖症患者数量的持续增加，脂肪细胞分散能量的潜在影响激发了人们对详细阐明这一生物学的热情，期望这一知识将为开发新的治疗方法提供基础，此外还将促进我们对细胞和分子生物学的总体理解。然而，在我们对指导这一重要过程的分子机制的理解上存在着知识差距。在我们对生理系统信号如何汇聚在这些机械路径上的理解中，还有一个额外的知识缺口。利用条件缺失小鼠模型，我们发现KLF15是米色脂肪细胞生成的有效调节因子。我们将使用最先进的分子和细胞生物学方法来揭示klf15调节这一过程的机制。

Adipose tissue has important implications for metabolism and general health. It is now well established that, rather than being a passive tissue for energy storage, as it was once perceived, adipose is a dynamic tissue that responds to changing physiological needs and systemic signals as well as secretes a variety of potent hormones with metabolic implications. The primary cell type within adipose tissue is the adipocyte and more recent advances have elucidated that there is heterogeneity in types of adipocytes, including divergent functional properties. Using cellular energetics to classify types of adipocytes defines two broad categories: adipocytes that store energy (‘white’ adipocytes) and adipocytes that disperse energy (‘brown’ adipocytes). Perhaps most intriguingly, more than one type of adipocyte can reside within a single adipose depot; in particular, within subcutaneous adipose depots in rodents, which are primarily white, there are also adipocytes that have properties of brown adipocytes, referred to as brown-in-white (‘brite’) or ‘beige’ adipocytes. Furthermore, the number of these adipocytes is dynamic, responding to changes in the systemic signals and environments. As the number of individuals with obesity continues to rise, the potential implications of adipocytes that disperse energy has generated enthusiasm for elucidating this biology in detail with the expectation that this knowledge will provide a foundation for the development of novel therapeutic approaches, in addition to advancing our understanding of cell and molecular biology in general. Yet, there is a knowledge gap in our understanding of the molecular mechanisms that direct this important process. There is an additional knowledge gap in our understanding of how physiological systemic signals converge on these mechanistic pathways. Using a conditional deletion mouse model, we identified Klf15 as a potent regulator of the generation of beige adipocytes. We will use state-of-the-art molecular and cell biology approaches to expose the mechanisms by which Klf15 regulates this process