Positive regulation by GABAbR1 subunit of leptin expression through gene transactivation in adipocytes

Yukari Kyumoto, Eiichi Hinoi, Takeshi Takarada, Yoshifumi Takahata, Tomomi Yamamoto, Hiroyuki Fujita, Saya Takada, Syota Hashizume, Yukio Yoneda

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: The view that γ-aminobutyric acid (GABA) plays a functional role in non-neuronal tissues, in addition to an inhibitory neurotransmitter role in the mammalian central nervous system, is prevailing, while little attention has been paid to GABAergic signaling machineries expressed by adipocytes to date. In this study, we attempted to demonstrate the possible functional expression of GABAergic signaling machineries by adipocytes. Methodology/Principal Findings: GABAB receptor 1 (GABABR1) subunit was constitutively expressed by mouse embryonic fibroblasts differentiated into adipocytes and adipocytic 3T3-L1 cells in culture, as well as mouse white adipose tissue, with no responsiveness to GABABR ligands. However, no prominent expression was seen with mRNA for GABABR2 subunit required for heteromeric orchestration of the functional GABABR by any adipocytic cells and tissues. Leptin mRNA expression was significantly and selectively decreased in adipose tissue and embryonic fibroblasts, along with drastically reduced plasma leptin levels, in GABABR1-null mice than in wild-type mice. Knockdown by siRNA of GABABR1 subunit led to significant decreases in leptin promoter activity and leptin mRNA levels in 3T3-L1 cells. Conclusions/Significance: Our results indicate that GABABR1 subunit is constitutively expressed by adipocytes to primarily regulate leptin expression at the transcriptional level through a mechanism not relevant to the function as a partner of heterodimeric assembly to the functional GABABR.

Original languageEnglish
Article numbere20167
JournalPloS one
Volume6
Issue number5
DOIs
Publication statusPublished - Jun 6 2011
Externally publishedYes

Fingerprint

transcriptional activation
Leptin
leptin
adipocytes
Adipocytes
Transcriptional Activation
Genes
Gene Expression
gene expression
Tissue
3T3-L1 Cells
receptors
mice
Fibroblasts
Messenger RNA
fibroblasts
Aminobutyrates
White Adipose Tissue
white adipose tissue
gamma-aminobutyric acid

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Kyumoto, Y., Hinoi, E., Takarada, T., Takahata, Y., Yamamoto, T., Fujita, H., ... Yoneda, Y. (2011). Positive regulation by GABAbR1 subunit of leptin expression through gene transactivation in adipocytes. PloS one, 6(5), [e20167]. https://doi.org/10.1371/journal.pone.0020167

Positive regulation by GABAbR1 subunit of leptin expression through gene transactivation in adipocytes. / Kyumoto, Yukari; Hinoi, Eiichi; Takarada, Takeshi; Takahata, Yoshifumi; Yamamoto, Tomomi; Fujita, Hiroyuki; Takada, Saya; Hashizume, Syota; Yoneda, Yukio.

In: PloS one, Vol. 6, No. 5, e20167, 06.06.2011.

Research output: Contribution to journalArticle

Kyumoto, Y, Hinoi, E, Takarada, T, Takahata, Y, Yamamoto, T, Fujita, H, Takada, S, Hashizume, S & Yoneda, Y 2011, 'Positive regulation by GABAbR1 subunit of leptin expression through gene transactivation in adipocytes', PloS one, vol. 6, no. 5, e20167. https://doi.org/10.1371/journal.pone.0020167
Kyumoto, Yukari ; Hinoi, Eiichi ; Takarada, Takeshi ; Takahata, Yoshifumi ; Yamamoto, Tomomi ; Fujita, Hiroyuki ; Takada, Saya ; Hashizume, Syota ; Yoneda, Yukio. / Positive regulation by GABAbR1 subunit of leptin expression through gene transactivation in adipocytes. In: PloS one. 2011 ; Vol. 6, No. 5.
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