title: Divergent effects of a designer natriuretic peptide CD-NP in the regulation of adipose tissue and metabolism.
abstract: Obesity is defined as an abnormal increase in white adipose tissue (WAT) and is a major risk factor for type 2 diabetes and cardiovascular disease. Brown adipose tissue (BAT) dissipates energy and correlates with leanness. Natriuretic peptides have been shown to be beneficial for brown adipocyte differentiation and browning of WAT.
  
  
  
  Here, we investigated the effects of an optimized designer natriuretic peptide (CD-NP) on murine adipose tissuesin vitroandin vivo.
  
  
  
  In murine brown and white adipocytes, CD-NP activated cGMP production, promoted adipogenesis, and increased thermogenic markers. Consequently, mice treated for 10 days with CD-NP exhibited increased "browning" of WAT. To study CD-NP effects on diet-induced obesity (DIO), we delivered CD-NP for 12 weeks. Although CD-NP reduced inflammation in WAT, CD-NP treated DIO mice exhibited a significant increase in body mass, worsened glucose tolerance, and hepatic steatosis. Long-term CD-NP treatment resulted in an increased expression of the NP scavenging receptor (NPR-C) and decreased lipolytic activity.
  
  
  
  NP effects differed depending on the duration of treatment raising questions about the rational of natriuretic peptide treatment in obese patients.
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, Bonn, Germany; Bonn International Graduate School of Drug Sciences BIGSDrugS, University of Bonn, Bonn, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Glöde
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, Bonn, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Naumann
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, Bonn, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Gnad
authors.affiliation: Cardiorenal Research Laboratory, Department of Cardiovascular Diseases, Mayo Clinic, Rochester, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Cannone
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, Bonn, Germany.
authors.forename: Ana
authors.initials: A
authors.lastname: Kilic
authors.affiliation: Cardiorenal Research Laboratory, Department of Cardiovascular Diseases, Mayo Clinic, Rochester, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, Bonn, Germany; Bonn International Graduate School of Drug Sciences BIGSDrugS, University of Bonn, Bonn, Germany. Electronic address: alexander.pfeifer@uni-bonn.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Pfeifer
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism; D052438:Adipocytes, White / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D004032:Diet; D004546:Elapid Venoms / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism / Q000494:pharmacology*; D009765:Obesity / Q000209:etiology; D022722:Thermogenesis / Q000187:drug effects
chemical_list: C542600:CD-NP natriuretic peptide; D004546:Elapid Venoms; D020098:Natriuretic Peptide, C-Type
keywords: Adipocytes; Browning; Diet-induced obesity; Natriuretic peptides; cGMP