Novel Regulators of Adipogenesis

In adipose tissue research, "adipogenesis" is commonly used to refer to the process of adipocyte formation, spanning from stem cell commitment to the development of mature, functional adipocytes. Although, this term should encompass a wide range of processes beyond commitment and differentiation, to also include other stages of adipose tissue development such as hypertrophy, hyperplasia, angiogenesis, macrophage infiltration, polarization, etc... collectively, referred to herein as the adipogenic cycle. The term “differentiation”, conversely, should only be used to refer to the process by which committed stem cells progress through distinct phases of subsequent differentiation. Recognizing this distinction is essential for accurately interpreting research findings on the mechanisms and stages of adipose tissue development and function. Furthermore, adipogenesis is regulated by a wide range of both positive and negative factors, two of which–PKM2 and IRX3–have been recently characterized by the Bettaieb lab. Briefly, our results demonstrated that the deficiency of PKM2, a key rate-limiting glycolytic enzyme, enhances the development and maintenance of brown adipose tissue (BAT), as evidenced by increased markers of brown fat differentiation and function. In our second investigation, IRX3 overexpression in white adipocyte precursor cells led to the increased expression of various differentiation markers as well as brown-fat specific proteins. The latter suggests that IRX3 plays a critical role in regulating adipocyte fate and ultimately, function. Collectively, our findings indicate that both PKM2 and IRX3 play integral roles in regulating the complex process of adipogenesis.