Nat Commun-De novo adipocyte differentiation from Pdgfrβ+ preadipocytes protects against pathologic visceral adipose expansion in obesity.pdf

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 antidiabetic
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.