title: Fetal development of subcutaneous white adipose tissue is dependent on Zfp423.
abstract: Zfp423is a multi zinc-finger transcription factor expressed in preadipocytes and mature adipocytesin vivo. Our recent work has revealed a critical role forZfp423in maintaining the fate of white adipocytes in adult mice through suppression of the beige cell thermogenic gene program; loss ofZfp423in mature adipocytes of adult mice results in a white-to-beige phenotypic switch. However, the exact requirements ofZfp423in the fetal stages of early adipose developmentin vivohave not been clarified.
  
  
  
  Here, we utilize two models that confer adipose-specificZfp423inactivation during fetal adipose development (Adiponectin-Cre;Zfp423loxP/loxPandAdiponectin-rtTA; TRE-Cre;Zfp423loxP/loxP). We assess the impact of fetal adiposeZfp423deletion on the initial formation of adipose tissue and evaluate the metabolic consequences of challenging these animals with high-fat diet feeding.
  
  
  
  Deletion ofZfp423during fetal adipose development results in a different phenotype than is observed when deletingZfp423in adipocytes of adult mice. Inactivation of Zfp423 during fetal adipose development results in arrested differentiation, specifically of inguinal white adipocytes, rather than a white-to-beige phenotypic switch that occurs whenZfp423is inactivated in adult mice. This is likely explained by the observation thatadiponectindriven Cre expression is active at an earlier stage of the adipocyte life cycle during fetal subcutaneous adipose development than in adult mice. Upon high-fat diet feeding, obese adiposeZfp423-deficient animals undergo a pathological adipose tissue expansion, associated with ectopic lipid deposition and systemic insulin resistance.
  
  
  
  Our results reveal thatZfp423is essential for the terminal differentiation of subcutaneous white adipocytes during fetal adipose tissue development. Moreover, our data highlight the striking adverse effects of pathological subcutaneous adipose tissue remodeling on visceral adipose function and systemic nutrient homeostasis in obesity. Importantly, these data reveal the distinct phenotypes that can occur whenadiponectindriven transgenes are activated in fetal vs. adult adipose tissue.
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Mengle
authors.initials: M
authors.lastname: Shao
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Hepler
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Lavanya
authors.initials: L
authors.lastname: Vishvanath
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Karen A
authors.initials: KA
authors.lastname: MacPherson
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Napoleon C
authors.initials: NC
authors.lastname: Busbuso
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: Rana.Gupta@UTSouthwestern.edu.
authors.forename: Rana K
authors.initials: RK
authors.lastname: Gupta
mesh_terms: D052438:Adipocytes, White / Q000378:metabolism; D050156:Adipogenesis; D000273:Adipose Tissue / Q000166:cytology; D000069796:Adipose Tissue, Beige / Q000378:metabolism / Q000502:physiology; D052436:Adipose Tissue, White / Q000378:metabolism / Q000502:physiology; D050154:Adiposity; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology*; D059305:Diet, High-Fat; D047109:Fetal Development / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology; D051379:Mice / Q000196:embryology; D008822:Mice, Transgenic; D009765:Obesity / Q000378:metabolism; D050151:Subcutaneous Fat / Q000196:embryology* / Q000378:metabolism; D022722:Thermogenesis; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; C484557:Ebfaz protein, mouse; D014157:Transcription Factors
keywords: Adipogenesis; Insulin resistance; Obesity; Pparg; Preadipocytes; Subcutaneous adipocytes; Zfp423