title: Anti-inflammatory properties of bone morphogenetic protein 4 in human adipocytes.
abstract: BACKGROUND
  Obesity is characterized by increased adipocyte number and size as well as white adipose tissue (WAT) inflammation, which is fundamental for the development of insulin resistance and type-2 diabetes. These processes, regulated by various endocrine, paracrine and autocrine factors, are extensively studied with the hope to interfere and to inhibit weight gain and related complications in obese patients. Recent data suggest an important role of bone morphogenic protein 4 (BMP4) in the regulation of adipogenesis and development of obesity. BMP4 is a growth factor of the transforming growth factor-β superfamily. Initially, BMPs were identified as inducers of ectopic bone formation. It is now apparent, however, that these proteins have different pleiotropic developmental actions and including playing a role in white adipogenesis.
  
  
  RESULTS
  Here, we demonstrate that the expression of BMP4 in human WAT is negatively correlated to body mass index and to the expression of pro-inflammatory cytokines. In vitro, BMP4 expression in cultured human adipocytes is upregulated after induction of differentiation. Cells treated with exogenous BMP4 increased peroxisome proliferator-activated receptor γ (PPARγ) expression and significantly reduced the expression of pro-inflammatory cytokines including tumor necrosis factor α (TNF-α) and monocyte chemoattractant protein 1. TNF-α treatment of fully differentiated adipocytes resulted in downregulation of the expression of adipogenic genes and elevated expression of pro-inflammatory cytokines. Exogenous BMP4 addition significantly reduced the negative effect of TNF-α on the expression profile of adipocytes. Finally, treatment of human adipocytes with exogenous BMP4 reduced the adipocytes' chemoattractant potential and the migration of monocytes toward adipocyte-conditioned medium.
  
  
  CONCLUSIONS
  These results indicate that BMP4 is an important anti-inflammatory molecule, which may act through PPARγ and reduces TNF-α-mediated pro-inflammatory cytokine production in human adipocytes. Through its anti-inflammatory potential, BMP4 may serve as a protective factor for inflammation-related diseases such as insulin-tolerance or type-2 diabetes.
authors.affiliation: Division of Molecular Endocrinology, Medical Clinic III, Technische Universität Dresden, Dresden, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Baraban
authors.affiliation: Division of Molecular Endocrinology, Medical Clinic III, Technische Universität Dresden, Dresden, Germany.|Department of Clinical Pathobiochemistry, Institute of Clinical Chemistry and Laboratory Medicine, University Clinic, Technische Universität Dresden, Dresden, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Chavakis
authors.affiliation: CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co KG, Biberach an der Riß, Germany.
authors.forename: B S
authors.initials: BS
authors.lastname: Hamilton
authors.affiliation: Division of Molecular Endocrinology, Medical Clinic III, Technische Universität Dresden, Dresden, Germany.|Max Planck Institute of Molecular Cell Biology and Genetics, Shevchenko Lab, Dresden, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Sales
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Wabitsch
authors.affiliation: Division of Molecular Endocrinology, Medical Clinic III, Technische Universität Dresden, Dresden, Germany.
authors.forename: S R
authors.initials: SR
authors.lastname: Bornstein
authors.affiliation: Division of Molecular Endocrinology, Medical Clinic III, Technische Universität Dresden, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Ehrhart-Bornstein
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis; D052436:Adipose Tissue, White / Q000378:metabolism*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism* / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology*; D007333:Insulin Resistance; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D014409:Tumor Necrosis Factor-alpha