Positive regulation by GABA(B)R1 subunit of leptin expression through gene transactivation in adipocytes.

<h4>Background</h4>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...

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Autores principales: Yukari Nakamura, Eiichi Hinoi, Takeshi Takarada, Yoshifumi Takahata, Tomomi Yamamoto, Hiroyuki Fujita, Saya Takada, Syota Hashizume, Yukio Yoneda
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Publicado: Public Library of Science (PLoS) 2011
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spelling oai:doaj.org-article:66c1768203bb422fb56cf02bcde1a5ae2021-11-18T06:52:49ZPositive regulation by GABA(B)R1 subunit of leptin expression through gene transactivation in adipocytes.1932-620310.1371/journal.pone.0020167https://doaj.org/article/66c1768203bb422fb56cf02bcde1a5ae2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21655283/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>GABA(B) receptor 1 (GABA(B)R1) 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 GABA(B)R ligands. However, no prominent expression was seen with mRNA for GABA(B)R2 subunit required for heteromeric orchestration of the functional GABA(B)R 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 GABA(B)R1-null mice than in wild-type mice. Knockdown by siRNA of GABA(B)R1 subunit led to significant decreases in leptin promoter activity and leptin mRNA levels in 3T3-L1 cells.<h4>Conclusions/significance</h4>Our results indicate that GABA(B)R1 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 GABA(B)R.Yukari NakamuraEiichi HinoiTakeshi TakaradaYoshifumi TakahataTomomi YamamotoHiroyuki FujitaSaya TakadaSyota HashizumeYukio YonedaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 5, p e20167 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yukari Nakamura
Eiichi Hinoi
Takeshi Takarada
Yoshifumi Takahata
Tomomi Yamamoto
Hiroyuki Fujita
Saya Takada
Syota Hashizume
Yukio Yoneda
Positive regulation by GABA(B)R1 subunit of leptin expression through gene transactivation in adipocytes.
description <h4>Background</h4>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.<h4>Methodology/principal findings</h4>GABA(B) receptor 1 (GABA(B)R1) 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 GABA(B)R ligands. However, no prominent expression was seen with mRNA for GABA(B)R2 subunit required for heteromeric orchestration of the functional GABA(B)R 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 GABA(B)R1-null mice than in wild-type mice. Knockdown by siRNA of GABA(B)R1 subunit led to significant decreases in leptin promoter activity and leptin mRNA levels in 3T3-L1 cells.<h4>Conclusions/significance</h4>Our results indicate that GABA(B)R1 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 GABA(B)R.
format article
author Yukari Nakamura
Eiichi Hinoi
Takeshi Takarada
Yoshifumi Takahata
Tomomi Yamamoto
Hiroyuki Fujita
Saya Takada
Syota Hashizume
Yukio Yoneda
author_facet Yukari Nakamura
Eiichi Hinoi
Takeshi Takarada
Yoshifumi Takahata
Tomomi Yamamoto
Hiroyuki Fujita
Saya Takada
Syota Hashizume
Yukio Yoneda
author_sort Yukari Nakamura
title Positive regulation by GABA(B)R1 subunit of leptin expression through gene transactivation in adipocytes.
title_short Positive regulation by GABA(B)R1 subunit of leptin expression through gene transactivation in adipocytes.
title_full Positive regulation by GABA(B)R1 subunit of leptin expression through gene transactivation in adipocytes.
title_fullStr Positive regulation by GABA(B)R1 subunit of leptin expression through gene transactivation in adipocytes.
title_full_unstemmed Positive regulation by GABA(B)R1 subunit of leptin expression through gene transactivation in adipocytes.
title_sort positive regulation by gaba(b)r1 subunit of leptin expression through gene transactivation in adipocytes.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/66c1768203bb422fb56cf02bcde1a5ae
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