TY - JOUR
T1 - Zfp238 Regulates the Thermogenic Program in Cooperation with Foxo1
AU - Kita, Motoko
AU - Nakae, Jun
AU - Kawano, Yoshinaga
AU - Asahara, Hiroshi
AU - Takemori, Hiroshi
AU - Okado, Haruo
AU - Itoh, Hiroshi
N1 - Funding Information:
This work was supported by a grant for the 21 st Century COE Program “Center of Excellence for Signal Transduction Disease: Diabetes Mellitus as a Model” from the Ministry of Education, Culture, Sports, Science and Technology of Japan; Grants-in-Aid for Scientific Research for Priority Areas No. 18052013 from the Ministry of Education, Science, Sports, and Culture in Japan to J.N.; by Scientific Research on Innovative Areas; aMEXTGrant-in-Aid Project “Crosstalk between transcriptional control and energy pathways, mediated by hub metabolites” grant numbers 26116724 to J.N.; by IUHW Research Grants to J.N.; and by grants from Nippon Boehringer Ingelheim Co. Ltd. , Ono Pharmaceutical Co. Ltd. , and Kowa Co. Ltd. to H.I.
Publisher Copyright:
© 2019 The Author(s)
PY - 2019/2/22
Y1 - 2019/2/22
N2 - Obesity has become an explicit public health concern because of its relevance to metabolic syndrome. Evidence points to the significance of beige adipocytes in regulating energy expenditure. Here, using yeast two-hybrid screening, we show that Zfp238 is a Foxo1 co-repressor and that adipose-tissue-specific ablation of Zfp238 (Adipo-Zfp238KO)in mice leads to obesity, decreased energy expenditure, and insulin resistance under normal chow diet. Adipo-Zfp238KO inhibits induction of Ucp1 expression in subcutaneous adipose tissue upon cold exposure or CL316243, but not in brown adipose tissue. Furthermore, knockdown of Zfp238 in 3T3-L1 cells decreases Ucp1 expression in response to cool incubation or forskolin significantly compared with control cells. In contrast, overexpression of Zfp238 in 3T3-L1 cells significantly increases Ucp1 expression in response to forskolin. Finally, double knockdown of both Zfp238 and Foxo1 normalizes Ucp1 induction. These data suggest that Zfp238 in adipose tissue regulates the thermogenic program in cooperation with Foxo1.
AB - Obesity has become an explicit public health concern because of its relevance to metabolic syndrome. Evidence points to the significance of beige adipocytes in regulating energy expenditure. Here, using yeast two-hybrid screening, we show that Zfp238 is a Foxo1 co-repressor and that adipose-tissue-specific ablation of Zfp238 (Adipo-Zfp238KO)in mice leads to obesity, decreased energy expenditure, and insulin resistance under normal chow diet. Adipo-Zfp238KO inhibits induction of Ucp1 expression in subcutaneous adipose tissue upon cold exposure or CL316243, but not in brown adipose tissue. Furthermore, knockdown of Zfp238 in 3T3-L1 cells decreases Ucp1 expression in response to cool incubation or forskolin significantly compared with control cells. In contrast, overexpression of Zfp238 in 3T3-L1 cells significantly increases Ucp1 expression in response to forskolin. Finally, double knockdown of both Zfp238 and Foxo1 normalizes Ucp1 induction. These data suggest that Zfp238 in adipose tissue regulates the thermogenic program in cooperation with Foxo1.
KW - Diabetology
KW - Molecular Interaction
KW - Molecular Mechanism of Behavior
KW - Specialized Functions of Cells
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U2 - 10.1016/j.isci.2019.01.005
DO - 10.1016/j.isci.2019.01.005
M3 - Article
AN - SCOPUS:85066277311
SN - 2589-0042
VL - 12
SP - 87
EP - 101
JO - iScience
JF - iScience
ER -
