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1 Department of Physiological Science, University of California, Los Angeles, California, USA
2 Division of Endocrinology, Metabolism and Molecular Medicine, Charles R. Drew University, Los Angeles, California, USA
3 Division of Nephrology and Hypertension, Department of Medicine, University of California, Irvine, California, USA
* To whom correspondence should be addressed. E-mail: croberts{at}ucla.edu.
The present study was designed to examine the effects of lifestyle modification on key contributing factors to atherogenesis, including oxidative stress, inflammation, chemotaxis, and cell adhesion. Obese men (N=31), 15 of whom had metabolic syndrome were placed on a high-fiber, low-fat diet in a 3-week residential program where food was provided ad libitum and daily aerobic exercise was performed. In each subject, pre- and post-intervention fasting blood was drawn for circulating levels of serum lipids, glucose and insulin (for estimation of insulin sensitivity), oxidative stress generating enzyme myeloperoxidase (MPO) and marker 8-isoprostaglandin F2
(8-iso-PGF2), the inflammatory protein C-reactive protein (CRP), soluble intracellular adhesion molecule (sICAM)-1 as an indicator of endothelial activation, sP-selectin as a marker of platelet activation, the chemokine macrophage inflammatory protein-1 (MIP-1) and total matrix metalloproteinase-9 (MMP-9). Using subject sera and human aortic endothelial cell (HAEC) culture systems, vascular cell adhesion molecule-1 (VCAM-1) cell surface abundance and monocyte chemotactic protein-1 (MCP-1), nitric oxide (NO), superoxide, and hydrogen peroxide production were measured in vitro by fluorometric detection. Also determined in vitro was serum-induced, monocyte adhesion and monocyte chemotatic activity (MCA). After 3 weeks, significant reductions (p<0.05) in BMI, all serum lipids and lipid ratios, fasting glucose, insulin, homeostasis model assessment for insulin resistance, MPO, 8-iso-PGF2, CRP, sICAM-1, sP-selectin, MIP-1, and MMP-9 were noted. In vitro, serum-stimulated cellular VCAM-1 expression, MCP-1 production, and fluorometric detection of superoxide and hydrogen peroxide production decreased, while a concomitant increase in NO production was noted (all p<0.01). Additionally, both monocyte adhesion (p<0.05) and MCA (p<0.01) decreased. 9 of 15 were no longer positive for metabolic syndrome post-intervention. Intensive lifestyle modification may ameliorate CAD risk factor reduction in men with metabolic syndrome factors prior to reversal of obesity.
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