Bmp4 Promotes a Brown to White-like Adipocyte Shift

• Published in: Cell reports (Cambridge) Vol. 16; no. 8; pp. 2243 - 2258
• Main Authors: Modica, Salvatore, Straub, Leon G., Balaz, Miroslav, Sun, Wenfei, Varga, Lukas, Stefanicka, Patrik, Profant, Milan, Simon, Eric, Neubauer, Heike, Ukropcova, Barbara, Ukropec, Jozef, Wolfrum, Christian
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.08.2016; Elsevier
• Subjects: Adipocytes, Brown - cytology; Adipocytes, Brown - drug effects; Adipocytes, Brown - metabolism; Adipocytes, White - cytology; Adipocytes, White - drug effects; Adipocytes, White - metabolism; Adipogenesis - drug effects; Adipogenesis - genetics; Adipose Tissue, Brown - cytology; Adipose Tissue, Brown - drug effects; Adipose Tissue, Brown - metabolism; Adipose Tissue, White - cytology; Adipose Tissue, White - drug effects; Adipose Tissue, White - metabolism; Animals; Bone Morphogenetic Protein 4 - genetics; Bone Morphogenetic Protein 4 - metabolism; Bone Morphogenetic Protein 4 - pharmacology; Cell Differentiation; Cell Line, Transformed; Cyclic AMP - pharmacology; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Gene Expression Regulation; Humans; Insulin Resistance; Male; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; Mice; Mice, Inbred C57BL; Peroxisome Proliferator-Activated Receptors - genetics; Peroxisome Proliferator-Activated Receptors - metabolism; Signal Transduction; Smad Proteins - genetics; Smad Proteins - metabolism; Sterol Esterase - genetics; Sterol Esterase - metabolism; Thiazolidinediones - pharmacology
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.07.048

While 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. [Display omitted] •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 Modica et al. show that upon commitment of mesenchymal stem cells into adipogenic lineage, Bmp4 attenuates the acquisition and maintenance of a brown phenotype by reducing lipolysis and brown fat gene expression via Smad signaling. Consequently, brown adipose tissue function is impaired.