3-D adipocyte differentiation and peri-adipocyte collagen turnover

Peri-adipocyte extracellular matrix (ECM) remodeling is a key biological process observed during adipose tissue development and expansion. The genetic loss of a pericellular collagenase, MMP14 (also known as MT1-MMP), renders mice lipodystrophic with the accumulation of undigested collagen fibers in adipose tissues. MMP14 is not necessary for adipocyte differentiation (adipogenesis) per se under a conventional two-dimensional (2-D) culture condition; however, MMP14 plays a critical role in adipogenesis in vivo. The role of MMP14 in adipogenesis and adipocyte gene expression was uncovered in vitro only when tested within a three-dimensional (3-D) collagen gel, which recapitulated the in vivo ECM-rich environment. Studying adipogenesis in 3-D may serve as an effective experimental approach to bridge gaps in our understanding of in vivo adipocyte biology. Moreover, by assessing the content of collagen family members and their rate of degradation in adipose tissues, we should be able to better define the role of dynamic ECM remodeling in the pathogenesis of obesity and diabetes.