Early experimental obesity is associated with coronary endothelial dysfunction and oxidative stress

Offer Galili, Daniele Versari, Katherine J. Sattler, Monica L. Olson, Dallit Mannheim, Joseph P. McConnell, Alejandro R. Chade, Lilach O Lerman, Amir Lerman

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

Obesity is independently associated with increased cardiovascular risk. However, since established obesity clusters with various cardiovascular risk factors, configuring the metabolic syndrome, the early effects of obesity on vascular function are still poorly understood. The current study was designed to evaluate the effect of early obesity on coronary endothelial function in a new animal model of swine obesity. As to method, juvenile domestic crossbred pigs were randomized to either high-fat/high-calorie diet (HF) or normal chow diet for 12 wk. Coronary microvascular permeability and abdominal wall fat were determined by using electron beam computerized tomography. Epicardial endothelial function and oxidative stress were measured in vitro. Systemic oxidative stress, renin-angiotensin activity, leptin levels, and parameters of insulin sensitivity were evaluated. As a result, HF pigs were characterized by abdominal obesity, hypertension, and elevated plasma lysophosphatidylcholine and leptin in the presence of increased insulin sensitivity. Coronary endothelium-dependent vasorelaxation was reduced in HF pigs and myocardial microvascular permeability increased compared with those values in normal pigs. Systemic redox status in HF pigs was similar to that in normal pigs, whereas the coronary endothelium demonstrated higher content of superoxide anions, nitrotyrosine, and NADPH-oxidase subunits, indicating increased tissue oxidative stress. In conclusion, the current study shows that early obesity is characterized by increased vascular oxidative stress and endothelial dysfunction in association with increased levels of leptin and before the development of insulin resistance and systemic oxidative stress. Vascular dysfunction is therefore an early manifestation of obesity and might contribute to the increased cardiovascular risk, independently of insulin resistance.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number2
DOIs
StatePublished - Feb 2007

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Oxidative Stress
Obesity
Swine
Insulin Resistance
Leptin
Blood Vessels
Capillary Permeability
Endothelium
Abdominal Fat
Sus scrofa
Lysophosphatidylcholines
X Ray Computed Tomography
Abdominal Obesity
NADPH Oxidase
Angiotensins
High Fat Diet
Abdominal Wall
Renin
Vasodilation
Superoxides

Keywords

  • Endothelium
  • Leptin
  • Permeability
  • Vasodilation

ASJC Scopus subject areas

  • Physiology

Cite this

Early experimental obesity is associated with coronary endothelial dysfunction and oxidative stress. / Galili, Offer; Versari, Daniele; Sattler, Katherine J.; Olson, Monica L.; Mannheim, Dallit; McConnell, Joseph P.; Chade, Alejandro R.; Lerman, Lilach O; Lerman, Amir.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 292, No. 2, 02.2007.

Research output: Contribution to journalArticle

Galili, Offer ; Versari, Daniele ; Sattler, Katherine J. ; Olson, Monica L. ; Mannheim, Dallit ; McConnell, Joseph P. ; Chade, Alejandro R. ; Lerman, Lilach O ; Lerman, Amir. / Early experimental obesity is associated with coronary endothelial dysfunction and oxidative stress. In: American Journal of Physiology - Heart and Circulatory Physiology. 2007 ; Vol. 292, No. 2.
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