TY - JOUR
T1 - De novo adipocyte differentiation from Pdgfrβ+ preadipocytes protects against pathologic visceral adipose expansion in obesity
AU - Shao, Mengle
AU - Vishvanath, Lavanya
AU - Busbuso, Napoleon C.
AU - Hepler, Chelsea
AU - Shan, Bo
AU - Sharma, Ankit X.
AU - Chen, Shiuhwei
AU - Yu, Xinxin
AU - An, Yu A.
AU - Zhu, Yi
AU - Holland, William L
AU - Gupta, Rana K
N1 - Funding Information:
The authors are grateful to the members of the UTSW Touchstone Diabetes Center for useful discussions, and Drs. P. Scherer and C. Kusminski for critical reading of the manuscript. The authors thank the UTSW Animal Resource Center, Metabolic Phenotyping Core, Transgenic Core, Pathology Core, Live Cell Imaging Core, and Flow Cytometry Core for excellent guidance and assistance with experiments performed here. This study was supported by the Searle Scholars Program (Chicago, IL), American Heart Association (AHA) 15BGIA22460021, American Diabetes Association 1-17-IBS-181, and NIDDK R01 DK104789 to R.K.G., NIDDK R00-DK094973 and JDRF Award 5-CDA-2014-185-A-N to W.L.H., AHA postdoctoral fellowship 16POST26420136 to M.S., NIH NIGMS training grant T32 GM008203 and NIDDK F31 DK113696-01 to C.H., and NIDDK K99 DK114498 to Y.Z.
Publisher Copyright:
© The Author(s) 2018.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-018-03196-x
DO - 10.1038/s41467-018-03196-x
M3 - Article
C2 - 29497032
AN - SCOPUS:85042871505
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 890
ER -