Bmp4 Promotes a Brown to White-like Adipocyte Shift
Salvatore Modica,
Leon G. Straub,
Miroslav Balaz,
Wenfei Sun,
Lukas Varga,
Patrik Stefanicka,
Milan Profant,
Eric Simon,
Heike Neubauer,
Barbara Ukropcova,
Jozef Ukropec,
Christian Wolfrum
Affiliations
Salvatore Modica
Swiss Federal Institute of Technology, Department of Health Science, Institute of Food Nutrition and Health, Laboratory of Translational Nutrition Biology, Schwerzenbach 8603, Switzerland
Leon G. Straub
Swiss Federal Institute of Technology, Department of Health Science, Institute of Food Nutrition and Health, Laboratory of Translational Nutrition Biology, Schwerzenbach 8603, Switzerland
Miroslav Balaz
Swiss Federal Institute of Technology, Department of Health Science, Institute of Food Nutrition and Health, Laboratory of Translational Nutrition Biology, Schwerzenbach 8603, Switzerland
Wenfei Sun
Swiss Federal Institute of Technology, Department of Health Science, Institute of Food Nutrition and Health, Laboratory of Translational Nutrition Biology, Schwerzenbach 8603, Switzerland
Lukas Varga
Obesity section of Diabetes Laboratory, Institute of Experimental Endocrinology, Biomedical Research Center at the Slovak Academy of Sciences, 845 05 Bratislava, Slovakia
Patrik Stefanicka
Department of Otorhinolaryngology–Head and Neck Surgery, Faculty of Medicine and University Hospital, Comenius University, 811 02 Bratislava, Slovakia
Milan Profant
Department of Otorhinolaryngology–Head and Neck Surgery, Faculty of Medicine and University Hospital, Comenius University, 811 02 Bratislava, Slovakia
Obesity section of Diabetes Laboratory, Institute of Experimental Endocrinology, Biomedical Research Center at the Slovak Academy of Sciences, 845 05 Bratislava, Slovakia
Jozef Ukropec
Obesity section of Diabetes Laboratory, Institute of Experimental Endocrinology, Biomedical Research Center at the Slovak Academy of Sciences, 845 05 Bratislava, Slovakia
Christian Wolfrum
Swiss Federal Institute of Technology, Department of Health Science, Institute of Food Nutrition and Health, Laboratory of Translational Nutrition Biology, Schwerzenbach 8603, Switzerland
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.
