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

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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