Submitted on August 3, 2007
Accepted on October 9, 2007
CARDIOTROPHIN-1 IS EXPRESSED IN ADIPOSE TISSUE AND IT IS UP-REGULATED IN THE METABOLIC SYNDROME
Cristina Natal1, Maria Antonia Fortuno2, Patricia Restituto3, Maria Inmaculada Colina4, Javier Diez5, and Nerea Varo6*
1 Division of Cardiovascular Sciences. Laboratory of Hypertension and Metabolism., Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Navarra, Spain
2 Division of Cardiovascular Sciences. Laboratory of Hypertension and Metabolism, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Navarra, Spain
3 Department of Clinical Chemistry, University Clinic of Navarra, Pamplona, Navarra, Spain
4 Department of Internal Medicine, University Clinic of Navarra, Pamplona, Navarra, Spain
5 Division of Cardiovascular Sciences. Laboratory of Hypertensive Cardiopathy, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Navarra, Spain; Department of Cardiology and Cardiovascular Surgery, University Clinic of Navarra, Pamplona, Navarra, Spain
6 Division of Cardiovascular Sciences. Laboratory of Hypertension and Metabolism, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Navarra, Spain; Department of Clinical Chemistry, University Clinic of Navarra, Pamplona, Navarra, Spain
* To whom correspondence should be addressed. E-mail: nvaro{at}unav.es.
Adipose tissue is a target for (cardiotrophin-1) CT-1, a cytokine member of the interleukin-6 family of cytokines that is involved in cardiac growth and dysfunction. However, is it unknown whether adipocytes are a source of CT-1 and whether this cytokine is over-expressed 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 ATPIII 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 the differentiation time from pre-adipocyte to mature adipocyte in 3T3.L1 cells. Interestingly, 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. Importantly, 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, respectively p<0.05). Of interest, circulating levels of CT-1 associated with glucose levels (r=0.2, p<0.05).
Taken together our data suggest that adipose tissue can be recognised as a source of CT-1 which could account for the high circulating levels of this cytokine found in patients with MS.
