De novo adipocyte differentiation from Pdgfrβ + preadipocytes protects against pathologic visceral adipose expansion in obesity

Pathologic expansion of white adipose tissue (WAT) in obesity is characterized by adipocyte hypertrophy, inflammation, and fibrosis; however, factors triggering this maladaptive remodeling are largely unknown. Here, we test the hypothesis that the potential to recruit new adipocytes from Pdgfrβ + preadipocytes determines visceral WAT health in obesity. We manipulate levels of Pparg , the master regulator of adipogenesis, in Pdgfrβ + precursors of adult mice. Increasing the adipogenic capacity of Pdgfrβ + precursors through Pparg overexpression results in healthy visceral WAT expansion in obesity and adiponectin-dependent improvements in glucose homeostasis. Loss of mural cell Pparg triggers pathologic visceral WAT expansion upon high-fat diet feeding. Moreover, the ability of the TZD class of anti-diabetic drugs to promote healthy visceral WAT remodeling is dependent on mural cell Pparg . These data highlight the protective effects of de novo visceral adipocyte differentiation in these settings, and suggest Pdgfrβ + adipocyte precursors as targets for therapeutic intervention in diabetes.