| 1. |
Hinoi E., Nakamura Y., Takada S., Fujita H., Iezaki T., Hashizume S., Takahashi S., Odaka Y., Watanabe T., Yoneda Y., Growth differentiation factor-5 promotes brown adipogenesis in systemic energy expenditure., Diabetes, 63, 1, 162-175, 2014.01, Although growth differentiation factor-5 (GDF5) has been implicated in skeletal development and joint morphogenesis in mammals, little is known about its functionality in adipogenesis and energy homeostasis. Here, we show a critical role of GDF5 in regulating brown adipogenesis for systemic energy expenditure in mice. GDF5 expression was preferentially upregulated in brown adipose tissues from inborn and acquired obesity mice. Transgenic overexpression of GDF5 in adipose tissues led to a lean phenotype and reduced susceptibility to diet-induced obesity through increased systemic energy expenditure. Overexpression of GDF5 facilitated the development of brown fat-like cells, called brite or beige cells, along with the expression of uncoupling protein-1 in inguinal subcutaneous white adipose tissue. In mutant mice harboring the dominant-negative GDF5, marked impairment in energy expenditure and thermogenesis was seen under obesogenic conditions. Recombinant GDF5 promoted brown adipogenesis through the mothers against decapentaplegic homolog (Smad) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) pathways after activation of bone morphogenetic protein receptor (BMPR). These results suggest that brown adipogenesis and energy homeostasis are both positively regulated by the GDF5/BMPR/Smad/PGC-1α signaling pathway in adipose tissues. Modulation of these pathways might be an effective therapeutic strategy for obesity and type 2 diabetes.. |
| 2. |
Nakamura Y.*, Hinoi E.*, Iezaki T., Takada S., Hashizume S., Takahata Y., Tsuruta E., Takahashi S., Yoneda Y. , Repression of adipogenesis through promotion of Wnt/ß-catenin signaling by TIS7 up-regulated in adipocytes under hypoxia. , BBA Mol. Basis Dis., 1832, 1117-1128, 2013.08. |
| 3. |
Takarada T., Takarada-Iemata M., Takahata Y., Yamada D., Yamamoto T., Nakamura Y., Hinoi E., Yoneda Y. , Osteoclastogenesis is negatively regulated by D-serine produced by osteoblasts. , J. Cell. Physiol., 227, 3477-3487, 2012.10. |
| 4. |
Takahata Y., Hinoi E., Takarada T., Nakamura Y., Ogawa S., Yoneda Y., Positive regulation by GABA(B) receptor subunit-1 of chondrogenesis through acceleration of nuclear translocation of activating transcription factor-4., J. Biol. Chem., 287, 33293-33303, 2012.09. |
| 5. |
Uno K., Takarada T., Takarada-Iemata M., Nakamura Y., Fujita H., Hinoi E., Yoneda Y. , Negative regulation of osteoblastogenesis through downregulation of runt-related transcription factor-2 in osteoblastic MC3T3-E1 cells with stable overexpression of the cystine/glutamate antiporter xCT subunit. , J. Cell. Physiol. , 226, 2953-2964, 2011.11. |
| 6. |
Takahata Y., Takarada T., Hinoi E., Nakamura Y., Fujita H., Yoneda Y. , Osteoblastic GABAB receptors negatively regulate osteoblastogenesis toward disturbance of osteoclastogenesis mediated by receptor activator of nuclear factor-kB ligand in mouse bone. , J. Biol. Chem., 286, 32906-32917, 2011.09. |
| 7. |
Takarada-Iemata M., Takarada T., Nakamura Y. Nakatani E., Hori O., Yoneda Y. , Glutamate preferentially suppresses osteoblastogenesis than adipogenesis through the cystine/glutamate antiporter in mesenchymal stem cells. , J. Cell. Physiol. , 226, 652-665, 2011.03. |
| 8. |
Nakamura Y.*, Hinoi E.*, Takarada T., Takahata Y., Yamamoto T., Fujita H., Takada S., Hashizume S., Yoneda Y., Positive regulation by GABABR1 subunit of leptin expression through gene transactivation in adipocytes., PLoS ONE. , 6, e20167, 2011.03. |
| 9. |
Uno K., Takarada T., Nakamura Y., Fujita H., Hinoi E., Yoneda Y., A negative correlation between expression profiles of runt-related transcription factor-2 and cystine/glutamate antiporter xCT subunit in ovariectomized mouse bone. , J. Pharmacol. Sci. , 115, 309-319, 2011.02. |
| 10. |
Nakamura Y.*, Takarada T.*, Kodama A., Hinoi E., Yoneda Y. , Predominant promotion by tacrolimus of chondrogenic differentiation to proliferating chondrocytes., J. Pharmacol. Sci. , 109, 413-423, 2009.03. |
| 11. |
Takahata Y., Takarada T., Osawa M., Hinoi E., Nakamura Y., Yoneda Y., Differential regulation of cellular maturation in chondrocytes and osteoblasts by glycine. , Cell Tissue Res. , 333, 91-103, 2008.07. |
