Adipose tissue from β-3 agonist-treated mice

We previously established the transcription factor Zfp423 is critical for maintaining white adipocyte identity through suppression of the thermogenic gene program. The loss of Zfp423 in mature adipocytes triggers the rapid conversion of energy-storing white adipocytes into thermogenic beige adipocytes in subcutaneous WAT. In contrast to subcutaneous WAT, visceral WAT is relatively resistant to browning. However, visceral adipocytes lacing Zfp423 are capable of inducing the thermogenic gene program upon β-3 adrenergic stimulus. Here, we generated mice lacking Zfp423 in visceral adipose by breeding transgenic mice expressing Cre recombinase under the control of the Wilms Tumor 1 locus (Wt1-Cre) to animals carrying the floxed Zfp423 alleles (Zfp423loxP/loxP) (“Vis-KO” mice). Inactivation of Zfp423 in visceral WAT gives rise to thermogenic adipocytes that share properties of subcutaneous beige adipocytes and classic brown adipocytes. In order to address whether deletion of Zfp423 in visceral adipose converts the white visceral adipocytes into bona fide subcutaneous beige adipocytes, we obtained and compared global gene expression profiles of adipose depots from control and Vis-KO animals through RNA sequencing. We treated the mice with vehicle (PBS) or β-3 adrenergic agonism (1 mg/kg CL316,243) daily for 3 days at thermoneutrality (30°C). RNA-sequencing was performed on mRNA libraries prepared from brown, gonadal, and inguinal adipose tissues from control mice (Cre negative), as well as from gonadal adipose tissue of Vis-KO animals