Integrative Cardiovascular Laboratories

Obesity and Metabolic Syndrome

Metabolic syndrome is characterized by upper body obesity, insulin resistance, hyperlipidemia, and hypertension, and represents a major and growing health problem in the United States. Endothelial dysfunction, due to impaired nitric oxide function, is a key feature promoting microvascular disease in resistance vessels, which contributes to hypertension during obesity and metabolic sydrome. The obese Zucker rat is a well established genetic model of obesity. Due to a non-functional leptin receptor gene and the consequent hyperphagia, these animals develop obesity and metabolic syndrome including insulin resistance, hyperlipidemia and hypertension. Previous studies have shown impaired endothelium-derived nitric oxide-dependent vasodilation in various vascular beds of obese Zucker rats, including skeletal muscle resistance vessels

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Metabolic syndrome represents a major cardiovascular risk factor, which is further enhanced by the increased chance of type 2 diabetes development. It is known that patients with type 2 diabetes show increased respiratory carbon monoxide levels. While elevated blood glucose levels in obese Zucker rats are not as prominent as some diabetes models, it appears that the elevated glucose, in conjunction with other obesity risk factors, promotes metabolic and developmental changes to increase carbon monoxide production which in turn contributes to the endothelial dysfunction by inhibiting nitric oxide synthesis.