Mol Metab-Fetal development of subcutaneous white adipose tissue is dependent on Zfp423.pdf Mengle Shao Chelsea Hepler Lavanya Vishvanath Karen A. MacPherson Napoleon Busbuso Rana Gupta 10.25376/hra.7800737.v1 https://hra.figshare.com/articles/journal_contribution/Mol_Metab-Fetal_development_of_subcutaneous_white_adipose_tissue_is_dependent_on_Zfp423_pdf/7800737 <div>Zfp423 is a multi zinc-finger transcription factor expressed in preadipocytes and mature adipocytes in vivo. Our recent work has</div><div>revealed a critical role for Zfp423 in maintaining the fate of white adipocytes in adult mice through suppression of the beige cell thermogenic gene</div><div>program; loss of Zfp423 in mature adipocytes of adult mice results in a white-to-beige phenotypic switch. However, the exact requirements of</div><div>Zfp423 in the fetal stages of early adipose development in vivo have not been clarified.Here, we utilize two models that confer adipose-specific Zfp423 inactivation during fetal adipose development (Adiponectin-Cre;</div><div>Zfp423loxP/loxP and Adiponectin-rtTA; TRE-Cre; Zfp423loxP/loxP). We assess the impact of fetal adipose Zfp423 deletion on the initial formation of</div><div>adipose tissue and evaluate the metabolic consequences of challenging these animals with high-fat diet feeding.Deletion of Zfp423 during fetal adipose development results in a different phenotype than is observed when deleting Zfp423 in adipocytes</div><div>of adult mice. Inactivation of Zfp423 during fetal adipose development results in arrested differentiation, specifically of inguinal white</div><div>adipocytes, rather than a white-to-beige phenotypic switch that occurs when Zfp423 is inactivated in adult mice. This is likely explained by the</div><div>observation that adiponectin driven Cre expression is active at an earlier stage of the adipocyte life cycle during fetal subcutaneous adipose</div><div>development than in adult mice. Upon high-fat diet feeding, obese adipose Zfp423-deficient animals undergo a pathological adipose tissue</div><div>expansion, associated with ectopic lipid deposition and systemic insulin resistance.Our results reveal that Zfp423 is essential for the terminal differentiation of subcutaneous white adipocytes during fetal adipose</div><div>tissue development. Moreover, our data highlight the striking adverse effects of pathological subcutaneous adipose tissue remodeling on visceral</div><div>adipose function and systemic nutrient homeostasis in obesity. Importantly, these data reveal the distinct phenotypes that can occur when</div><div>adiponectin driven transgenes are activated in fetal vs. adult adipose tissue.</div> 2019-03-04 22:01:42 Zfp423 PPAR γ Adipose tissue development Cell Biology