الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
 |  | from | 107 |  |  |
| | | from | 107 | | |
Abstract
Obesity is a growing epidemic worldwide; its prevalence has been rising tremendously over the last years. It results from the imbalance between energy intake and energy expenditure. It is associated with increased risk of human morbidity and mortality. It is a pro-inflammatory condition in which hypertrophied adipocytes and adipose tissue-resident immune cells (primarily lymphocytes and macrophages), both contribute to increased circulating levels of pro-inflammatory cytokines. The obesity-associated state of chronic low-grade systemic inflammation, termed “metabolic inflammation,” is considered a focal point in the pathogenesis of insulin resistance and T2DM in humans and rodent animal models.
Insulin resistance is defined as the decreased peripheral tissue response to insulin-mediated cellular actions and the term “insulin resistance” refers also to reduced whole-body glucose uptake in response to physiological levels of insulin. It correlates strongly with central-visceral obesity but not with lower body (i.e., hip, lower extremity) obesity. It is strongly associated with the etiology of T2DM, metabolic syndrome, hypertension and coronary heart disease.
Among all environmental influences, both high-fat diet and lack of or decline in daily physical activity are the most important factors for obesity development. Rats and mice fed a high fat diet have increased visceral fat accumulation, whole body and muscle insulin resistance, and compensatory hyperinsulinemia within 4 weeks. Excessive intake of dietary fat promotes adipocyte hypertrophy, altering their normal endocrine function to an inflammatory pathologic condition that increases the secretion of TNF-α and IL-6, and concomitantly reducing adiponectin secretion. TNF-α is a potent pro-inflammatory cytokine, secreted mainly by adipose tissue-resident macrophages in obese individuals. TNF-α induces insulin resistance mainly by defective phosphorylation of insulin receptor substrate 1. This reduces the expression of glucose transporters and adiponectin in adipocytes, which contributes to the development of insulin resistance.
DHEA is a natural steroid that serves as a precursor of male and female sex hormones. It is produced from the adrenal gland, and together with its sulfated form (DHEA-S), are the most abundant steroid hormones in humans. Patients with metabolic syndrome have lower DHEA and DHEA-S levels. The obesity and type 2 diabetes patients show lower concentrations of DHEA and other sex steroid hormone. There is evidence that DHEA administration improves insulin sensitivity, reduces fat mass and normalizes glucose metabolism
Exercise training is considered an important environmental factor associated with body weight regulation and has shown to control obesity and weight gain and to improve insulin sensitivity and help in reducing the risk of diabetes.
The present study was carried to investigate the possible effects of muscular exercise, DHEA and their combination on insulin sensitivity, TNF-α in high fat diet fed rats.
The study was conducted on 40 adult male Albino rats with bodyweight of approximately 100-150g. All rats were fed on high fat diet (60% fat, 20% carbohydrate and 20% protein) for 14 weeks, throughout the experimental period, animals had free access to food and water. Body weight was measured at the end of the 8th week and those who had 10% increase in their body weight or more had continued the last 6 weeks of the experiment.