Document Detail


Sfrp5 is an anti-inflammatory adipokine that modulates metabolic dysfunction in obesity.
MedLine Citation:
PMID:  20558665     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adipose tissue secretes proteins referred to as adipokines, many of which promote inflammation and disrupt glucose homeostasis. Here we show that secreted frizzled-related protein 5 (Sfrp5), a protein previously linked to the Wnt signaling pathway, is an anti-inflammatory adipokine whose expression is perturbed in models of obesity and type 2 diabetes. Sfrp5-deficient mice fed a high-calorie diet developed severe glucose intolerance and hepatic steatosis, and their adipose tissue showed an accumulation of activated macrophages that was associated with activation of the c-Jun N-terminal kinase signaling pathway. Adenovirus-mediated delivery of Sfrp5 to mouse models of obesity ameliorated glucose intolerance and hepatic steatosis. Thus, in the setting of obesity, Sfrp5 secretion by adipocytes exerts salutary effects on metabolic dysfunction by controlling inflammatory cells within adipose tissue.
Authors:
Noriyuki Ouchi; Akiko Higuchi; Koji Ohashi; Yuichi Oshima; Noyan Gokce; Rei Shibata; Yuichi Akasaki; Akihiko Shimono; Kenneth Walsh
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-06-17
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  329     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-23     Completed Date:  2010-08-09     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  454-7     Citation Subset:  IM    
Affiliation:
Molecular Cardiology and Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118, USA. nouchi@bu.edu
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MeSH Terms
Descriptor/Qualifier:
3T3-L1 Cells
Adipocytes / metabolism*,  pathology
Adipokines / genetics,  metabolism*
Adipose Tissue / metabolism*,  pathology
Animals
Dietary Fats / administration & dosage
Dietary Sucrose / administration & dosage
Fatty Liver / pathology,  therapy
Genetic Vectors
Glucose / metabolism
Humans
Inflammation
Insulin / metabolism
Insulin Resistance
Intercellular Signaling Peptides and Proteins / genetics,  metabolism*
Macrophages / metabolism*
Mice
Mice, Inbred C57BL
Mice, Obese
Mitogen-Activated Protein Kinase 8 / genetics,  metabolism
Obesity / metabolism*,  pathology
Phosphorylation
Rats
Rats, Zucker
Signal Transduction
Wnt Proteins / metabolism
Grant Support
ID/Acronym/Agency:
AG15052/AG/NIA NIH HHS; AG34972/AG/NIA NIH HHS; HL81587/HL/NHLBI NIH HHS; HL86785/HL/NHLBI NIH HHS; P01 HL081587-05/HL/NHLBI NIH HHS; R01 AG015052-06/AG/NIA NIH HHS; R01 AG034972-03/AG/NIA NIH HHS; R01 HL086785-19/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Adipokines; 0/Dietary Fats; 0/Dietary Sucrose; 0/Intercellular Signaling Peptides and Proteins; 0/Sfrp5 protein, mouse; 0/Wnt Proteins; 0/Wnt5a protein, mouse; 11061-68-0/Insulin; 50-99-7/Glucose; EC 2.7.11.24/Mitogen-Activated Protein Kinase 8
Comments/Corrections
Comment In:
Nat Rev Drug Discov. 2010 Aug;9(8):594   [PMID:  20671761 ]
Science. 2010 Jul 23;329(5990):397-8   [PMID:  20651140 ]
Nat Rev Immunol. 2010 Aug;10(8):540   [PMID:  20672476 ]

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