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

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