The regulation of energy metabolism by brown-adipokine

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Although the growth differentiate factor 5 (GDF5) has been implicated in skeletal development in mammal, little attention has been paid to the functionality in adipogenesis and energy homeostasis. Here, we show a critical role of the GDF5 in regulating both brown adipogenesis and whole-body energy expenditure. Transgenic mice overexpressing GDF5 in adipose tissues not only showed a lean phenotype but protection against high fat diet-induced obesity due to increased energy expenditure. On the contrary, mutant mice harboring dominant-negative form of GDF5 have impaired energy expenditure and thermogenesis on obesogenic condition. GDF5 activated brown adipogenesis through bone morphological protein receptor (BMPR) pathway. Taken together, these findings demonstrate that GDF5/BMPR pathway regulates brown adipogenesis and energy homeostasis and suggest that modulation of this pathway might be a plausible strategy for obesity and metabolic dysfunctions.