Mural Cell Zfp423 in Control of Adipose Remodeling in Obesity

Ut Southwestern Medical Center, Dallas TX

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Abstract

Project Summary The manner by which adipose tissue remodels during obesity is a key determinant of metabolic health. Expansion through the formation of new adipocytes (hyperplasia) is more metabolically favorable than through the enlargement of existing adipocytes (hypertrophy). Moreover, individuals that store excess adipose tissue preferentially in the subcutaneous region (typically females) have a lower risk of developing metabolic syndrome than those that store adipose tissue predominately in the visceral region (typically males). Our lab has recently identified cells of mural origin that contribute to adipogenesis in the gonadal depot of the male mouse during high fat diet feeding. However, the contribution of these cells to other adipose depots in male mice, as well as in female mice, has not been explored. In this proposal, we aim to characterize mural cell adipogenesis in subcutaneous and gonadal adipose depots in male as well as female mice. This will shed insight into the differential regulation of adipogenesis in a sex- and depot-dependent manner. Mural preadipocyte cells can be identified by the expression of Zfp423. Zfp423 is a transcription factor that regulates Ppar?, the master regulator of adipogenesis. Using novel inducible gain- and loss-of-function mouse models, we propose to investigate the functional role of Zfp423 in mural cell adipogenesis in adult mice. We hypothesize that Zfp423 is necessary and sufficient to stimulate healthy adipocyte hyperplasia during high fat diet feeding. The experiments in this proposal will explore the unique metabolic outcomes of manipulating adipose tissue remodeling during obesity. Moreover, these studies will uncover new insight into the regulation of adipogenesis in the adult.