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

doi:10.1016/j.celrep.2016.07.048

Bmp4 Promotes a Brown to White-like Adipocyte Shift

Cell Rep. 2016 Aug 23;16(8):2243-2258. doi: 10.1016/j.celrep.2016.07.048. Epub 2016 Aug 11.

Authors

Affiliations

¹ Swiss Federal Institute of Technology, Department of Health Science, Institute of Food Nutrition and Health, Laboratory of Translational Nutrition Biology, Schwerzenbach 8603, Switzerland.
² 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.
³ Department of Otorhinolaryngology-Head and Neck Surgery, Faculty of Medicine and University Hospital, Comenius University, 811 02 Bratislava, Slovakia.
⁴ Target Discovery Research, Boehringer Ingelheim Pharma, 88400 Biberach/Riss, Germany.
⁵ CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma, 88400 Biberach/Riss, Germany.
⁶ 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.
⁷ Obesity section of Diabetes Laboratory, Institute of Experimental Endocrinology, Biomedical Research Center at the Slovak Academy of Sciences, 845 05 Bratislava, Slovakia.
⁸ 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: [email protected].

PMID: 27524617
DOI: 10.1016/j.celrep.2016.07.048

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.

MeSH terms

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 Stem Cells / cytology
Mesenchymal Stem Cells / drug effects
Mesenchymal Stem Cells / metabolism
Mice
Mice, Inbred C57BL
Peroxisome Proliferator-Activated Receptors / genetics
Peroxisome Proliferator-Activated Receptors / metabolism
Rosiglitazone
Signal Transduction
Smad Proteins / genetics
Smad Proteins / metabolism
Sterol Esterase / genetics
Sterol Esterase / metabolism
Thiazolidinediones / pharmacology

Substances

Bmp4 protein, mouse
Bone Morphogenetic Protein 4
Peroxisome Proliferator-Activated Receptors
Smad Proteins
Thiazolidinediones
Rosiglitazone
Cyclic AMP
Sterol Esterase