Obesity is associated with increased levels of circulating hepatocyte growth factor

• Published in: Journal of the American College of Cardiology 2003-04, Vol.41 (8), p.1408-1413
• Main Authors: Rehman, Jalees, Considine, Robert V., Bovenkerk, Jason E., Li, Jingling, Slavens, Catharine A., Jones, Rose Marie, March, Keith L.
• Format: Article
• Language: English
• Subjects: Adipocytes - metabolism; Adult; Biological and medical sciences; Body Mass Index; Cardiology; Coronary Disease - etiology; Coronary Disease - metabolism; Endothelial Growth Factors - blood; Endothelial Growth Factors - metabolism; Enzyme-Linked Immunosorbent Assay; Female; Hepatocyte Growth Factor - blood; Hepatocyte Growth Factor - metabolism; Humans; Insulin resistance; Intercellular Signaling Peptides and Proteins - blood; Intercellular Signaling Peptides and Proteins - metabolism; Lymphokines - blood; Lymphokines - metabolism; Male; Medical sciences; Metabolic diseases; Obesity; Obesity - blood; Obesity - complications; Obesity - metabolism; Research Design; Rodents; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Weight control
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/S0735-1097(03)00231-6

This study evaluated whether obesity in humans was associated with an increase in circulating hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) levels. Obesity acts as a cardiovascular risk factor by mechanisms that are not fully understood. Adipose tissue is able to secrete multiple cytokines and growth factors ex vivo. We hypothesized that the increased presence of adipose tissue in obese subjects results in systemic elevations of the mitogenic factors HGF and VEGF. Blood samples were obtained from lean (n = 21) and obese (n = 44) volunteers. Serum HGF and VEGF levels were assessed by enzyme-linked immunoadsorbent assay. Insulin and fasting glucose levels were measured to evaluate insulin sensitivity. Conditioned medium of adipose cells was assayed for HGF secretion. Serum HGF levels in obese subjects were more than three-fold higher than those of lean subjects (2,462 ± 184 pg/ml vs. 765 ± 48 pg/ml, p < 0.0001). The VEGF levels were not significantly elevated in obese subjects (135 ± 31 pg/ml vs. 128 ± 37 pg/ml). The HGF concentrations, but not VEGF concentrations, were significantly correlated with body mass index (BMI) (p < 0.0001, r = 0.74). The observed increases in HGF concentrations of obese subjects were not secondary to insulin resistance or hypertension. Freshly isolated human adipose cells secreted HGF. Our results indicate that obesity is associated with a marked increase in circulating HGF levels, which correlate linearly with BMI. Because vascular growth factors have been associated with the pathogenesis of atherosclerosis, the possible role of such humoral factors as a link between obesity and cardiovascular disease is very intriguing.