EXPEDITED REVIEW
Obesity is associated with increased levels of circulating hepatocyte growth factor
Jalees Rehman, MD* ,
Robert V. Considine, PhD ,
Jason E. Bovenkerk, MS,
Jingling Li, MS*,
Catharine A. Slavens, BS*,
Rose Marie Jones, MD and
Keith L. March, MD, PhD, FACC*,*
* Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana, USA
Division of Endocrinology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
Indiana Center for Vascular Biology and Medicine, Indianapolis, Indiana, USA
Department of Surgery, St. Vincent’s Hospital, Carmel, Indiana, USA
Manuscript received December 12, 2002;
revised manuscript received February 14, 2003,
accepted February 20, 2003.
* Reprint requests and correspondence: Dr. Keith L. March, Indiana Center for Vascular Biology and Medicine and Krannert Institute of Cardiology, 975 W. Walnut Street, IB 441, Indianapolis, Indiana 46202, USA.
kmarch{at}iupui.edu
OBJECTIVES: 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.
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
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Abbreviations and Acronyms
| | ASC | | adipose stromal cells | | BMI | | body mass index | | BP | | blood pressure | | DBP | | diastolic blood pressure | | HGF | | hepatocyte growth factor | | HOMA | | Homeostatic Model Assessment | | LFT | | liver function tests | | SBP | | systolic blood pressure | | VEGF | | vascular endothelial growth factor |
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