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
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Figure 1 Obesity was associated with significant elevations of circulating hepatocyte growth factor (HGF) (A) but not of circulating vascular endothelial growth factor (VEGF) (B) in obese subjects when compared with lean subjects. Data are presented as mean ± SEM, and the analysis was performed using a t test. A value of p > 0.05 was considered not significant (NS).
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Figure 2 The serum levels of hepatocyte growth factor (HGF) (A) were significantly correlated with body mass index (BMI) as determined by linear regression analysis. To maintain the scale of the graph, three obese patients with HGF concentrations in the 4,000 to 6,500 pg/ml range are omitted from this graph. However, they are included in the statistical analysis. Circulating vascular endothelial growth factor (VEGF) levels (B), on the other hand, were not correlated with the degree of obesity. A value of p > 0.05 was considered not significant (NS). Open squares = lean subjects; solid circles = obese subjects.
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Figure 3 Obese patients were subdivided into three groups according to their insulin sensitivity using a Homeostatic Model Assessment (HOMA) score (normal insulin sensitivity with HOMA score <3; moderate insulin resistance with HOMA score between 3 and 5; and severe insulin resistance with HOMA score >5). The mean serum HGF levels of these three groups did not differ significantly using analysis of variance (A). There was also no significant correlation between the degree of insulin resistance (HOMA score) and hepatocyte growth factor (HGF) concentrations (B). There was a nonsignificant trend toward lower HGF levels with higher insulin resistance. A value of p > 0.05 was considered not significant (NS).
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Figure 4 Because hypertension can affect hepatocyte growth factor (HGF) levels and hypertension has a higher prevalence among obese subjects, hypertension could act as a confounding factor. Therefore, we excluded all subjects with either known hypertension or documented hypertension at the time of blood draw (either systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg). The difference in mean serum HGF levels between the remaining obese and lean subjects continued to be highly significant (A). Furthermore, the correlation between body mass index and HGF levels was even stronger in this group of subjects (B). Open squares = lean subjects; solid circles = obese subjects.
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Figure 5 (A) The reverse transcription-polymerase chain reaction technique demonstrates that freshly isolated human adipocytes and non-adipocyte adipose stromal cells (ASCs) express hepatocyte growth factor (HGF). The expression appears to be less than that of liver tissue, when comparable amounts of total deoxyribonucleic acid (see glyceraldehyde-3-phosphate dehydrogenase as control) are used. (B) Adipocytes and ASCs can also secrete HGF protein into conditioned media, and achieve biologically active HGF concentrations in the media, which are substantially higher than those of cultured human aortic endothelial cells (HAECs).
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Copyright © 2003 by the American College of Cardiology Foundation.
