Study of the Role of Obesity and Estrogen Deficiency on Functions of Insulin Sensitive Tissues and the Underlying Genetic Machinery
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- Category: Vol. 78, September 2010
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Study of the Role of Obesity and Estrogen Deficiency on Functions of Insulin Sensitive Tissues and the Underlying Genetic Machinery,THANAA G. TADROS, MAGED A. HAROUN, HEBA M. SHAWKY and MONA M. MOHAMED
Abstract
Glucose homeostasis is maintained by interplay between the pancreas and insulin sensitive tissues. In this study, we investigated alteration of insulin receptor sensitivity and/or responsiveness (post receptor function) induced by obesity and estrogen deficiency and the impact of estrogen supple-mentation following ovariectomy on the specific cellular genetic machinery of the adipose tissue, diaphragm and liver. Fifty adult female rats were included in this study, divided into five groups (n=10/group): Control (group I), zucker obese (group II), high fat diet (HFD)-obese (group III), ovariecto-mized (group IV) and ovariectomized-estrogen treated (group V). Fasting glucose, lipids and insulin were measured as well as the glucose uptake by the visceral adipose tissue and diaphragm and the liver glucose output. Gene expression of ofPI3K and PPARy in these tissues was also assessed. Zuker obese rats revealed receptor defect, whereas HFD-induced obesity showed both receptor and post receptor dysfunctions with reduction in expression of PI3K and PPARy.These defects resulted in hyperglycemia, hyperlipidemia and hyperinsuline-mia which finally induced Insulin resistance (IR). Estrogen deficiency induced by overiactomy resulted in alteration in both receptor and post receptor functions with reduction in adipose PPARy expression. Estrogen replacement increased PPARy expression in adipose tissue, muscle and liver.
In Conclusion: The observed metabolic abnormalities that induced IR could be attributed to alteration in receptor and/or post receptor functions as well as signaling pathways of PI3K and PPARy. However, adipose PPARy could be considered as a reliable marker that reflects insulin sensitization of its target tissues.