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Am J Physiol Endocrinol Metab 294: E52-E60, 2008. First published October 16, 2007; doi:10.1152/ajpendo.00506.2007
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Cardiotrophin-1 is expressed in adipose tissue and upregulated in the metabolic syndrome

Cristina Natal,1 María Antonia Fortuño,1 Patricia Restituto,2 Antonio Bazán,3 Immaculada Colina,4 Javier Díez,1,5 and Nerea Varo1,2

1Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, and Departments of 2Clinical Chemistry, 3Department of Plastic Surgery, University Clinic of Navarra, Pamplona, Spain, 4Internal Medicine, and 5Cardiology and Cardiovascular Surgery (JD), University Clinic of Navarra, Pamplona, Spain

Submitted 3 August 2007 ; accepted in final form 9 October 2007

Adipose tissue is a target for cardiotrophin-1 (CT-1), a cytokine member of the IL-6 family of cytokines that is involved in cardiac growth and dysfunction. However, it is unknown whether adipocytes are a source of CT-1 and whether CT-1 is overexpressed in diseases characterized by increased fat depots [i.e., the metabolic syndrome (MS)]. Thus this work aimed 1) to test whether adipose tissue expresses CT-1 and whether CT-1 expression can be modulated and 2) to compare serum CT-1 levels in subjects with and without MS diagnosed by National Cholesterol Education Program Adult Treatment Panel III criteria. Gene and protein expression of CT-1 was determined by real-time RT-PCR, ELISA, and Western blotting. CT-1 expression progressively increased, along with differentiation time from preadipocyte to mature adipocyte in 3T3-L1 cells. CT-1 expression was enhanced by glucose in a dose-dependent manner in these cells. mRNA and protein CT-1 expression was also demonstrated in human adipose biopsies. Immunostaining showed positive staining in adipocytes. Finally, increased CT-1 serum levels were observed in patients with MS compared with control subjects (127 ± 9 vs. 106 ± 4 ng/ml, P < 0.05). Circulating levels of CT-1 were associated with glucose levels (r = 0.2, P < 0.05). Taken together, our data suggest that adipose tissue can be recognized as a source of CT-1, which could account for the high circulating levels of CT-1 in patients with MS.

cytokines; obesity; diabetes



Address for reprint requests and other correspondence: N. Varo, Center for Applied Medical Research, Avda Pío XII 55, 31008 Pamplona, Spain (e-mail: nvaro{at}unav.es)







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