| RRC ID |
30757
|
| 著者 |
Hinoi E, Iezaki T, Fujita H, Watanabe T, Odaka Y, Ozaki K, Yoneda Y.
|
| タイトル |
PI3K/Akt is involved in brown adipogenesis mediated by growth differentiation factor-5 in association with activation of the Smad pathway.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
We have previously demonstrated promotion by growth differentiation factor-5 (GDF5) of brown adipogenesis for systemic energy expenditure through a mechanism relevant to activating the bone morphological protein (BMP) receptor/mothers against decapentaplegic homolog (Smad)/peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α) pathway. Here, we show the involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in brown adipogenesis mediated by GDF5. Overexpression of GDF5 in cells expressing adipocyte protein-2 markedly accelerated the phosphorylation of Smad1/5/8 and Akt in white and brown adipose tissues. In brown adipose tissue from heterozygous GDF5(Rgsc451) mutant mice expressing a dominant-negative (DN) GDF5 under obesogenic conditions, the basal phosphorylation of Smad1/5/8 and Akt was significantly attenuated. Exposure to GDF5 not only promoted the phosphorylation of both Smad1/5/8 and Akt in cultured brown pre-adipocytes, but also up-regulated Pgc1a and uncoupling protein-1 expression in a manner sensitive to the PI3K/Akt inhibitor Ly294002 as well as retroviral infection with DN-Akt. GDF5 drastically promoted BMP-responsive luciferase reporter activity in a Ly294002-sensitive fashion. Both Ly294002 and DN-Akt markedly inhibited phosphorylation of Smad5 in the nuclei of brown pre-adipocytes. These results suggest that PI3K/Akt signals play a role in the GDF5-mediated brown adipogenesis through a mechanism related to activation of the Smad pathway.
|
| 巻・号 |
450(1)
|
| ページ |
255-60
|
| 公開日 |
2014-7-18
|
| DOI |
10.1016/j.bbrc.2014.05.108
|
| PII |
S0006-291X(14)00997-8
|
| PMID |
24944017
|
| MeSH |
Adipogenesis / physiology*
Adipose Tissue, Brown / cytology*
Adipose Tissue, Brown / physiology*
Animals
Cell Differentiation / physiology
Cells, Cultured
Growth Differentiation Factor 5 / metabolism*
Mice
Mice, Transgenic
Oncogene Protein v-akt / metabolism*
Phosphatidylinositol 3-Kinases / metabolism*
Signal Transduction / physiology
Smad Proteins / metabolism*
|
| IF |
2.985
|
| 引用数 |
22
|
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| 実験動物マウス |
GSC0080 |
