title: Bmp4 Promotes a Brown to White-like Adipocyte Shift.
abstract: 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.
authors.affiliation: Swiss Federal Institute of Technology, Department of Health Science, Institute of Food Nutrition and Health, Laboratory of Translational Nutrition Biology, Schwerzenbach 8603, Switzerland.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Modica
authors.affiliation: Swiss Federal Institute of Technology, Department of Health Science, Institute of Food Nutrition and Health, Laboratory of Translational Nutrition Biology, Schwerzenbach 8603, Switzerland.
authors.forename: Leon G
authors.initials: LG
authors.lastname: Straub
authors.affiliation: Swiss Federal Institute of Technology, Department of Health Science, Institute of Food Nutrition and Health, Laboratory of Translational Nutrition Biology, Schwerzenbach 8603, Switzerland.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Balaz
authors.affiliation: Swiss Federal Institute of Technology, Department of Health Science, Institute of Food Nutrition and Health, Laboratory of Translational Nutrition Biology, Schwerzenbach 8603, Switzerland.
authors.forename: Wenfei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Obesity section of Diabetes Laboratory, Institute of Experimental Endocrinology, Biomedical Research Center at the Slovak Academy of Sciences, 845 05 Bratislava, Slovakia; Department of Otorhinolaryngology-Head and Neck Surgery, Faculty of Medicine and University Hospital, Comenius University, 811 02 Bratislava, Slovakia.
authors.forename: Lukas
authors.initials: L
authors.lastname: Varga
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Faculty of Medicine and University Hospital, Comenius University, 811 02 Bratislava, Slovakia.
authors.forename: Patrik
authors.initials: P
authors.lastname: Stefanicka
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Faculty of Medicine and University Hospital, Comenius University, 811 02 Bratislava, Slovakia.
authors.forename: Milan
authors.initials: M
authors.lastname: Profant
authors.affiliation: Target Discovery Research, Boehringer Ingelheim Pharma, 88400 Biberach/Riss, Germany.
authors.forename: Eric
authors.initials: E
authors.lastname: Simon
authors.affiliation: CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma, 88400 Biberach/Riss, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Neubauer
authors.affiliation: Obesity section of Diabetes Laboratory, Institute of Experimental Endocrinology, Biomedical Research Center at the Slovak Academy of Sciences, 845 05 Bratislava, Slovakia; Institute of Pathophysiology, Faculty of Medicine, Comenius University, 811 02 Bratislava, Slovakia.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ukropcova
authors.affiliation: Obesity section of Diabetes Laboratory, Institute of Experimental Endocrinology, Biomedical Research Center at the Slovak Academy of Sciences, 845 05 Bratislava, Slovakia.
authors.forename: Jozef
authors.initials: J
authors.lastname: Ukropec
authors.affiliation: Swiss Federal Institute of Technology, Department of Health Science, Institute of Food Nutrition and Health, Laboratory of Translational Nutrition Biology, Schwerzenbach 8603, Switzerland. Electronic address: christian-wolfrum@ethz.ch.
authors.forename: Christian
authors.initials: C
authors.lastname: Wolfrum
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052438:Adipocytes, White / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052436:Adipose Tissue, White / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D000242:Cyclic AMP / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism; D000077154:Rosiglitazone; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D002787:Sterol Esterase / Q000235:genetics / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D047492:Peroxisome Proliferator-Activated Receptors; D051785:Smad Proteins; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000242:Cyclic AMP; D002787:Sterol Esterase