UCLA

Bone morphogenetic protein (BMP) signaling is intricately involved in adipose tissue development. BMP7 together with BMP4 have been implicated in brown adipocyte differentiation but their roles during adipose development have been difficult to fully specify. Matrix Gla protein (MGP) is an effective inhibitor of both BMP4 and BMP7, and is expressed in adipose endothelial and progenitor cells. Global and cell-specific Mgp gene deletion in combination with RNA analysis, immunostaining, thermogenic activity, and in vitro studies revealed that MGP directs brown adipose tissue development at two essential steps. Endothelial-derived MGP limits the triggering of white adipogenic differentiation in the perivascular region of brown adipose tissue (BAT), whereas MGP derived from adipose cells supports the transition of CD142-expressing progenitor cells to brown adipogenic maturity. Both steps were important to optimize the thermogenic function of BAT. In addition, MGP derived from the respective locations impacted the adipose vascular growth. The reduction of MGP in either endothelial or adipose cells expanded the endothelial cell population, suggesting that MGP is a factor in the overall plasticity of adipose tissue. Thus, MGP models a dual and cell-specific function in BAT, essentially creating a "cellular shuttle" that drives the brown adipogenic differentiation in coordination with vascular growth during development.