Accumulation of visceral fat leads to insulin resistance and diabetes. Therefore, it is important to elucidate the mechanism by which adipose progenitor cells (APCs) are maintained and how they differentiate. The bHLH transcription factor 21 (Tcf21) is expressed in visceral, but not in subcutaneous fat, and used as a marker for white adipose tissues. Although Tcf21 promotes IL6 expression in APCs in vitro, little is known about its role in vivo. Therefore, we aimed to clarify the role of Tcf21 in visceral fat using mouse models. Tcf21 was deleted after birth using inducible Cre-LoxP system to circumvent the lethality due to cardiac malformation (iTcf21 KO). The mice were fed high fat diet (HFD) from 6 to 24 weeks of age. Weight gain, blood glucose level, epididymal fat weight, and APC count (0.8x104/g fat for iKO and 2.9x104/g fat for wild type (WT)) of epididymal fat were all low in iTcf21KO compared to WT mice. Insulin sensitivity was increased in iTcf21KO mice. Staining of epididymal fat from Tcf21lacZ/+ mice using X-Gal revealed that Tcf21 was localized in the vascular mural cells. Isolation of Sca1+ Lin- APCs using magnetic activated cell sorting revealed that Tcf21 mRNA was expressed in the APCs, along with Pdgfrb and Periostin. In contrast, Tcf21 expression was attenuated in the adipose tissue of WT mice after HFD, and in adipocyte culture that was differentiated from the vascular stromal fraction (SVF). In addition, Tcf21 expression suppressed by HFD was upregulated in adipocytes undergoing de-differentiation by ceiling culture. Adipocyte induction from SVF resulted in no differences between WT and iTcf21KO mice assessed by oil red O staining. However, adipocyte differentiation and expression of Pparg and Cebpb were suppressed in 3T3-L1 cells in which Tcf21 was overexpressed. These findings suggest that Tcf21 is expressed in the APCs of vascular mural cells, controls the number of APCs, and potentially contributes to the maintenance of their progenitor state through suppression of adipocyte differentiation.


T. Minamizuka: None. Y. Maezawa: None. H. Udagawa: None. Y. Baba: None. M. Koshizaka: None. Y. Endo: None. K. Yasuda: None. K. Yokote: Research Support; Self; Astellas Pharma Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi K.K., Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited. Speaker’s Bureau; Self; Abbott, Astellas Amgen, AstraZeneca K.K., Bayer Inc., FUJIFILM Pharmaceuticals U.S.A., Inc., Kaken Pharmaceutical Co., Ltd., Sanwa Kagaku Kenkyusho.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at