Positive regulation by GABA(B)R1 subunit of leptin expression through gene transactivation in adipocytes.
Positive regulation by GABA(B)R1 subunit of leptin expression through gene transactivation in adipocytes.
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DOI：
10.1371/journal.pone.0020167
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Yoneda Y
中科院分区：
文献类型：
--
作者：
Nakamura Y;Hinoi E;Takarada T;Takahata Y;Yamamoto T;Fujita H;Takada S;Hashizume S;Yoneda Y
γ-氨基丁酸除了在哺乳动物中枢神经系统中发挥抑制性神经递质作用外，还在非神经组织中发挥功能作用，而对脂肪细胞表达的GABA能信号机制迄今关注较少。在这项研究中，我们试图证明GABA能信号机制在脂肪细胞中可能的功能表达。小鼠胚胎成纤维细胞分化为脂肪细胞和脂肪细胞3T3-L1细胞，以及小鼠白色脂肪组织中，GABAB受体1亚基(GABABR1)呈结构性表达，对GABABR配体无反应性。然而，任何脂肪细胞和组织都没有看到GABABR2亚基的显著表达，这是任何脂肪细胞和组织异构体协调功能GABABR所需的。与野生型小鼠相比，GABABR1基因缺失小鼠的脂肪组织和胚胎成纤维细胞中瘦素mRNA的表达显著和选择性地降低，同时血浆瘦素水平显著降低。GABABR1亚单位的siRNA抑制3T3-L1细胞的瘦素启动子活性和瘦素mRNA水平。我们的结果表明，GABABR1亚基是由脂肪细胞结构性表达的，主要是通过一种与作为功能GABABR的异源二聚体组装伙伴的功能无关的机制在转录水平上调节瘦素的表达。
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. 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. 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.
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影响因子：
4.8
作者：
Hollenberg, AN;Susulic, VS;Lowell, BB
通讯作者：
Lowell, BB
DOI：
10.1073/pnas.93.12.5793
发表时间：
1996-06-11
影响因子：
11.1
作者：
Kallen, CB;Lazar, MA
通讯作者：
Lazar, MA
影响因子：
64.8
作者：
Jordan, BA;Devi, LA
通讯作者：
Devi, LA
影响因子：
4.9
作者：
Fuke, T.;Yoshizaki, T.;Maegawa, H.
通讯作者：
Maegawa, H.
影响因子：
64.8
作者：
Kaupmann, K;Huggel, K;Bettler, B
通讯作者：
Bettler, B