TY - JOUR
T1 - The CCR4–not deadenylase complex maintains adipocyte identity
AU - Takahashi, Akinori
AU - Takaoka, Shohei
AU - Kobori, Shungo
AU - Yamaguchi, Tomokazu
AU - Ferwati, Sara
AU - Kuba, Keiji
AU - Yamamoto, Tadashi
AU - Suzuki, Toru
N1 - Funding Information:
Funding: This work was supported by a Grant-in-Aid for Scientific Research (S) (21229006), Scientific Research (C) (17K07292, 18K07079), JSPS Fellows (10J08349), Young Scientists (B) (25860761) from Japan Society for the Promotion of Science, and Scientific Research in Innovative Areas, Research in a proposed research area (25121734, 17H06018) from the Japan Ministry of Education, Culture, Sports, Science and Technology.
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Shortening of poly(A) tails triggers mRNA degradation; hence, mRNA deadenylation regulates many biological events. In the present study, we generated mice lacking the Cnot1 gene, which encodes an essential scaffold subunit of the CCR4–NOT deadenylase complex in adipose tissues (Cnot1-AKO mice) and we examined the role of CCR4–NOT in adipocyte function. Cnot1-AKO mice showed reduced masses of white adipose tissue (WAT) and brown adipose tissue (BAT), indicating abnormal organization and function of those tissues. Indeed, Cnot1-AKO mice showed hyperinsulinemia, hyperglycemia, insulin resistance, and glucose intolerance and they could not maintain a normal body temperature during cold exposure. Muscle-like fibrous material appeared in both WAT and BAT of Cnot1-AKO mice, suggesting the acquisition of non-adipose tissue characteristics. Gene expression analysis using RNA-sequencing (RNA-seq) showed that the levels of adipose tissue-related mRNAs, including those of metabolic genes, decreased, whereas the levels of inflammatory response-related mRNAs increased. These data suggest that the CCR4–NOT complex ensures proper adipose tissue function by maintaining adipocyte-specific mRNAs at appropriate levels and by simultaneously suppressing mRNAs that would impair adipocyte function if overexpressed.
AB - Shortening of poly(A) tails triggers mRNA degradation; hence, mRNA deadenylation regulates many biological events. In the present study, we generated mice lacking the Cnot1 gene, which encodes an essential scaffold subunit of the CCR4–NOT deadenylase complex in adipose tissues (Cnot1-AKO mice) and we examined the role of CCR4–NOT in adipocyte function. Cnot1-AKO mice showed reduced masses of white adipose tissue (WAT) and brown adipose tissue (BAT), indicating abnormal organization and function of those tissues. Indeed, Cnot1-AKO mice showed hyperinsulinemia, hyperglycemia, insulin resistance, and glucose intolerance and they could not maintain a normal body temperature during cold exposure. Muscle-like fibrous material appeared in both WAT and BAT of Cnot1-AKO mice, suggesting the acquisition of non-adipose tissue characteristics. Gene expression analysis using RNA-sequencing (RNA-seq) showed that the levels of adipose tissue-related mRNAs, including those of metabolic genes, decreased, whereas the levels of inflammatory response-related mRNAs increased. These data suggest that the CCR4–NOT complex ensures proper adipose tissue function by maintaining adipocyte-specific mRNAs at appropriate levels and by simultaneously suppressing mRNAs that would impair adipocyte function if overexpressed.
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U2 - 10.3390/ijms20215274
DO - 10.3390/ijms20215274
M3 - Article
C2 - 31652943
AN - SCOPUS:85074177836
SN - 1661-6596
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 21
M1 - 5274
ER -