10.25376/hra.7800743.v1 Mengle Shao Mengle Shao Lavanya Vishvanath Lavanya Vishvanath Napoleon Busbuso Napoleon Busbuso Chelsea Hepler Chelsea Hepler Bo Shan Bo Shan Ankit Sharma Ankit Sharma Shiuhwei Chen Shiuhwei Chen Xinxin Yu Xinxin Yu Yu An Yu An Yi Zhu Yi Zhu William Holland William Holland Rana Gupta Rana Gupta Nat Commun-De novo adipocyte differentiation from Pdgfrβ+ preadipocytes protects against pathologic visceral adipose expansion in obesity.pdf Health Research Alliance 2019 Adipose tissue hyperplasia Adipose tissue remodeling Preadipocyte Adipose mural cell Metabolic Medicine 2019-03-04 22:01:42 Journal contribution https://hra.figshare.com/articles/journal_contribution/Nat_Commun-De_novo_adipocyte_differentiation_from_Pdgfr_preadipocytes_protects_against_pathologic_visceral_adipose_expansion_in_obesity_pdf/7800743 <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>