Bmp4 Promotes a Brown to White-like Adipocyte Shift

• Bmp4 promotes differentiation of brown pre-adipocytes into white-like adipocytes
• Bmp4 blunts the activity of mature brown adipocytes
• Ectopic expression of Bmp4 in brown adipose tissue reduces energy expenditure
• Obese type 2 diabetic subjects have higher levels of circulating BMP4

SummaryWhile Bmp4 has a well-established role in the commitment of mesenchymal stem cells into the adipogenic lineage, its role in brown adipocyte formation and activity is not well defined. Here, we show that Bmp4 has a dual function in adipogenesis by inducing adipocyte commitment while inhibiting the acquisition of a brown phenotype during terminal differentiation. Selective brown adipose tissue overexpression of Bmp4 in mice induces a shift from a brown to a white-like adipocyte phenotype. This effect is mediated by Smad signaling and might be in part due to suppression of lipolysis, via regulation of hormone sensitive lipase expression linked to reduced Ppar activity. Given that we observed a strong correlation between BMP4 levels and adipocyte size, as well as insulin sensitivity in humans, we propose that Bmp4 is an important factor in the context of obesity and type 2 diabetes.

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