The transcriptional modulator Ifrd1 controls PGC-1α expression under short-term adrenergic stimulation in brown adipocytes

Gyujin Park, Tetsuhiro Horie, Takashi Kanayama, Kazuya Fukasawa, Takashi Iezaki, Yuki Onishi, Kakeru Ozaki, Yukari Kyumoto, Yukio Yoneda, Takeshi Takarada, Eiichi Hinoi

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Abstract

Sympathetic tone activates the function of classical brown adipocytes, which constitutively exist in the brown adipose tissue (BAT), and inducible brown adipocytes (so-called beige adipocytes), which sporadically reside within the white adipose tissue (WAT). Here we identified the transcriptional modulator interferon-related developmental regulator 1 (Ifrd1) as a negative regulator of thermogenic and mitochondrial gene expression in brown adipocytes. Ifrd1 expression was markedly induced by cold exposure and administration of CL-316243 (a β3 adrenergic agonist) in interscapular brown adipose and inguinal subcutaneous WATs, but not in epididymal visceral WAT, in vivo. Adrenergic stimulation also induced Ifrd1 expression in brown adipocytes in a cAMP responsive element binding protein-dependent manner in vitro. CL-316243 injection markedly elevated thermogenic and mitochondrial gene expression, including peroxisome proliferator-activated receptor γ coactivator 1α (Pgc1a) in the subcutaneous WAT of Ifrd1 knockout mice compared with gene expression in wild-type mice. Pgc1a promoter activity enhanced by the transcription factor specificity protein 1 (Sp1) was markedly repressed by co-introduction of Ifrd1 in brown adipocytes, whereas the repression was markedly prevented by the addition of trichostatin A, a histone deacetylase inhibitor. Moreover, adrenergic stimulation induced complex formation between Ifrd1, Sp1 and mSIN3B, which is a component of the SIN complex containing histone deacetylase, in brown adipocytes. These findings, therefore, suggest that Ifrd1 could be a pivotal negative regulator of sympathetic regulation of thermogenic and mitochondrial gene expression in brown adipocytes by interacting with Sp1 and the mSIN3 complex.

Original languageEnglish
Pages (from-to)784-795
Number of pages12
JournalFEBS Journal
Volume284
Issue number5
DOIs
Publication statusPublished - Mar 1 2017

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Brown Adipocytes
Adrenergic Agents
Interferons
Modulators
Gene expression
White Adipose Tissue
Mitochondrial Genes
Tissue
Gene Expression
trichostatin A
Sp1 Transcription Factor
Adrenergic Agonists
Peroxisome Proliferator-Activated Receptors
Histone Deacetylase Inhibitors
Brown Adipose Tissue
Histone Deacetylases
Intra-Abdominal Fat
Groin
Subcutaneous Fat
Regulator Genes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Park, G., Horie, T., Kanayama, T., Fukasawa, K., Iezaki, T., Onishi, Y., ... Hinoi, E. (2017). The transcriptional modulator Ifrd1 controls PGC-1α expression under short-term adrenergic stimulation in brown adipocytes. FEBS Journal, 284(5), 784-795. https://doi.org/10.1111/febs.14019

The transcriptional modulator Ifrd1 controls PGC-1α expression under short-term adrenergic stimulation in brown adipocytes. / Park, Gyujin; Horie, Tetsuhiro; Kanayama, Takashi; Fukasawa, Kazuya; Iezaki, Takashi; Onishi, Yuki; Ozaki, Kakeru; Kyumoto, Yukari; Yoneda, Yukio; Takarada, Takeshi; Hinoi, Eiichi.

In: FEBS Journal, Vol. 284, No. 5, 01.03.2017, p. 784-795.

Research output: Contribution to journalArticle

Park, G, Horie, T, Kanayama, T, Fukasawa, K, Iezaki, T, Onishi, Y, Ozaki, K, Kyumoto, Y, Yoneda, Y, Takarada, T & Hinoi, E 2017, 'The transcriptional modulator Ifrd1 controls PGC-1α expression under short-term adrenergic stimulation in brown adipocytes', FEBS Journal, vol. 284, no. 5, pp. 784-795. https://doi.org/10.1111/febs.14019
Park, Gyujin ; Horie, Tetsuhiro ; Kanayama, Takashi ; Fukasawa, Kazuya ; Iezaki, Takashi ; Onishi, Yuki ; Ozaki, Kakeru ; Kyumoto, Yukari ; Yoneda, Yukio ; Takarada, Takeshi ; Hinoi, Eiichi. / The transcriptional modulator Ifrd1 controls PGC-1α expression under short-term adrenergic stimulation in brown adipocytes. In: FEBS Journal. 2017 ; Vol. 284, No. 5. pp. 784-795.
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