Response to Cardiotrophin-1 in Adolescents: Impact of Obesity and Blood Pressure
We read with interest the letter from Jung et al1 providing data on the potential impact of overweight/obesity and blood pressure on cardiotrophin-1 (CT-1) levels in adolescents. We saw that they found no differences in plasma CT-1 levels between overweight/obese and normal-weight adolescents and neither overweight/obesity indices nor HBA1c and adiponectin correlated with plasma levels of CT-1.
In our study, the high plasma CT-1 in morbidly obese patients might possibly be attributable both to the degree of weight excess and to the duration of obesity. It has been demonstrated recently that the CT-1 gene and protein expression progressively increase with the differentiation time from preadipocyte to mature adipocyte in murine 3T3.L1 cells. mRNA and protein CT-1 expression have also been reported in human adipose biopsies.2 These data, therefore, suggest that adipose tissue can be a source of CT-1 and other adipocytokines, which could account for the high circulating levels of this cytokine in obese patients with the related metabolic complications. Moreover, in long-standing obesity there is an upregulation of many inflammation-related genes in white adipose tissue,3 leading to higher circulating levels of adipocytokines.
Therefore, it has been proposed that obesity-related cardiometabolic complications are at least partly a chronic inflammatory consequence of a disease starting in the adipose tissue. However, Jung et al1 may have underestimated the future cardiometabolic risk of obese adolescents, because the adolescents will very likely continue to gain weight for several decades.
Our study discussed the possible pathophysiological role of CT-1 in left ventricular growth. It has been suggested that, other than hemodynamic load, the process that leads to left ventricular hypertrophy may also depend on protracted activity of cytokines, among other nonhemodynamic factors.4 We did in fact suggest that, in a situation of chronic volume overload–induced hypertrophy, such as obesity, enhancement of CT-1 production by cardiac myocytes is hypothetically possible. It has been demonstrated that cardiac abnormalities (left ventricular hypertrophy and diastolic dysfunction) are present also in normotensive, morbidly obese adolescents, but they improve with marked weight loss.5 Therefore, it would be interesting to investigate plasma CT-1 levels and cardiac phenotype (by echocardiography) as additional useful indicators in the initial cardiac assessment of overweight/obese adolescents.
Sources of Funding
The present work was partially supported by grants from First 60%, University of Milan, and from Prin, Rome.
Jung C, Fritzenwanger M, Figulla HR. Cardiotrophin-1 in adolescents: impact of obesity and blood pressure. Hypertension. 2008; 52: e6.
Natal C, Fortuno MA, Restituto P, Bazan A, Colina I, Diez J, Varo N. Cardiotrophin-1 is expressed in adipose tissue and upregulated in the metabolic syndrome. Am J Physiol Endoc Metab. 2008; 294: E52–E60.
de Simone G, Pasanisi F, Contaldo F. Link of nonhemodynamic factors to hemodynamic determinants of left ventricular hypertrophy. Hypertension. 2001; 38: 13–18.