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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook_2014     Display Documents

ID: 682181.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook_2014
Increased cGMP promotes healthy expansion and browning of white adipose tissue
Authors:Mitschke, M. M.; Hoffmann, L. S.; Gnad, T.; Scholz, D.; Kruithoff, K.; Mayer, P.; Haas, B.; Sassmann, A.; Pfeifer, A.; Kilic, A.
Date of Publication (YYYY-MM-DD):2013-04
Journal Abbrev.:FASEB J
Issue / Number:4
Start Page:1621
End Page:1630
Audience:Not Specified
Abstract / Description:With more than half a billion individuals affected worldwide, obesity has reached pandemic proportions. Development of "brown-like" or "brite" adipocytes within white adipose tissue (WAT) has potential antiobesity and insulin-sensitizing effects. We investigated the role of cyclic GMP (cGMP) signaling, focusing on cGMP-dependent protein kinase I (PKGI) in WAT. PKGI is expressed in murine WAT, primary adipocytes, and 3T3-L1. Treatment of adipocytes with cGMP resulted in increased adipogenesis, with a 54% increase in expression of peroxisome proliferator-activated receptor-gamma. Lentiviral overexpression of PKGI further increased adipogenesis, whereas loss of PKGI significantly reduced adipogenic differentiation. In addition to adipogenic effects, PKGI had an antihypertrophic and anti-inflammatory effect via RhoA phosphorylation and reduction of proinflammatory adipokine expression. Moreover, PKGI induced a 4.3-fold increase in abundance of UCP-1 and the development of a brown-like thermogenic program in primary adipocytes. Notably, treatment of C57BL/6 mice with phosphodiesterase inhibitor sildenafil (12 mg/kg/d) for 7 d caused 4.6-fold increase in uncoupling protein-1 expression and promoted establishment of a brown fat cell-like phenotype ("browning") of WAT in vivo. Taken together, PKGI is a key regulator of cell size, adipokine secretion and browning of white fat depots and thus could be a valuable target in developing novel treatments for obesity.
Free Keywords:3T3-L1 Cells/cytology; Adipocytes/metabolism; *Adipogenesis; Adipose Tissue, Brown/cytology/*metabolism; Adipose Tissue, White/cytology/*metabolism; Animals; Cyclic GMP/*metabolism; Cyclic GMP-Dependent Protein Kinases/metabolism; Ion Channels/metabolism; Mice; Mice, Inbred C57BL; Mitochondria/metabolism; Mitochondrial Proteins/metabolism; Obesity/metabolism; Signal Transduction
External Publication Status:published
Document Type:Article
Communicated by:Svea Hümmer
Affiliations:MPI für physiologische und klinische Forschung
Identifiers:ISSN:1530-6860 (Electronic) 0892-6638 (Linking) %R 10.1096/fj.12-221580
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