Abstract 605: Bone Morphogenetic Protein Inhibitors Play Important Roles in Brown and White Adipogenesis
Adipose tissue is intimately connected to the development of metabolic syndrome, type 2 diabetes and cardiovascular disease. The near pandemic increase in incidence and prevalence of obesity makes it necessary to understand adipose regulation in order to develop strategies against obesity and its comorbidities. Adipose tissue performs a variety of functions. White adipose tissue (WAT) is responsible for energy storage, hormone production and organ protection, whereas brown adipose tissue (BAT) has a key role in thermogenesis. Previous studies have shown the importance of Bone Morphogenetic Proteins (BMPs) in the differentiation of brown and white adipocytes. BMP4 has been linked to both brown and white adipogenesis and BMP7 is essential for brown adipogenesis. Nevertheless, the role of the BMP inhibitors, which modulate the actions of BMPs, has not yet been elucidated. Our hypothesis is that the BMP inhibitors play important roles in the adipogenic process. Using two different mice models -Matrix Gla Protein (Mgp) KO and Noggin fat-specific KO- we found that the absence of Mgp resulted in dramatic adipose changes, suggesting a critical role in the separation of white and brown adipocytes. Adipocyte-specific deletion of Noggin, however, suggested a role in modulating the size and lipid accumulation in fully differentiated adipocytes. The absence of Mgp led to a reduction in body fat and body weight (3-12 animals per group and time point) whereas the absence of Noggin caused an increase in body fat and body weight (4-18 animals per time point and body weight). Tissue culture experiments using white and brown adipocyte progenitor cells showed specific temporal patterns of the BMPs and BMP-inhibitors that were consistent with the mouse findings. In conclusion, BMP inhibitors are essential in distinguishing brown and white adipogenic differentiation. We hypothesize that MGP is critical in the initial separation, whereas Noggin regulates cell size and lipid accumulation.