© 2005 Elsevier España, S.A. The Metabolic Syndrome is characterized by insulin resistance and a combination of abdominal obesity, hypertriglyceridemia, low HDL, fasting hyperglycemia and hypertension. Insulin resistance occurs in peripheral tissues such as skeletal muscle and adipose tissue, and in the liver. The metabolic function of a specific gene product may be determined in animal models by increasing or decreasing its expression in a tissue of interest. Adipose tissue is the main site of fat storage, but it also secretes factors which affect insulin sensitivity, lipid homeostasis and blood pressure. In genetically engineered mice, alterations in glucose metabolism, insulin signaling or triglyceride synthesis lead to obesity and alterations in other tissues, thus affecting glucose homeostasis. A disruption in adipose tissue lipolysis or re-/esterification also results in alteration in lipid deposition and may lead to insulin resistance. The liver is a key tissue for glucose uptake and storage and defective hepatic glucose uptake may have a role in the pathogenesis of insulin resistance. Moreover, transgenic mice with an increase in hepatic gluconeogenesis demonstrate that excessive hepatic glucose output is a major factor responsible for the elevated plasma glucose concentration. Studies with transgenic and knock-out mice clearly show an inverse relationship between hepatic lipid content and insulin sensitivity. This indicates that lipid deposition in the liver may cause hepatic insulin resistance and contribute to the development of the Metabolic Syndrome. Skeletal muscle insulin-stimulated glucose uptake has been altered specifically in rodent models by genetic engineering. Results arising from these animal models suggest that skeletal muscle defects may induce whole-body insulin resistance. Thus, functional alterations in liver, skeletal muscle and adipose tissue may contribute to the development of the Metabolic Syndrome. This review illustrates the application of transgenic and knock-out technologies to the study of the Metabolic Syndrome and describes several key animal models.
|Title of host publication||The Metabolic Syndrome at the Beginning of the XXI Century: A Genetic and Molecular Approach|
|Number of pages||15|
|Publication status||Published - 11 Nov 2005|