الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Obesity and related metabolic disorders are associated with increased risk of cardiovascular disease.
To date, 7 angiopoietin like proteins (Angptls) that are structurally similar to angiopoietins have been identified. Some Angptls potently regulate angiogenesis, where as others, have pleiotropic activities independent of their effects on angiogenesis such as regulation of lipid and glucose metabolism. The most functional member of the Angptl family regarding their role in glucose and lipid metabolism and insulin sensitivity is Angptl6 (AGF).
The objective of this study is to evaluate the relation between testosterone level and insulin sensitivity in a group of obese men and to search for a possible role of AGF in this Patho-physiologic link.
Sixty male subjects aged between 40-60 years were included in the present study, divided as follows:
Group I (normal): Twenty lean men, body mass index ≤ 25 kg/m2.
Group II (overweight): Fifteen overweight men, body mass index 26-29 kg/m2.
Group III (obese): Twenty five obese men, body mass index ≥ 30 kg/m2.
All subjects involved in the present study were selected to be free from any hepatic, collagenic, cardiac, renal and pulmonary diseases, as well as from diabetes and any inflammatory or malignant conditions. Those receiving any medications will be excluded from the study.
To all the studied subjects, the following were done:
• Height and weight were measured to calculate BMI and WHR.
• Laboratory investigations: including; Fasting serum samples for determination of the following:
• Glucose (and two hours post prandial serum glucose).
• Lipid profile.
• Alanine and aspartate aminotransferases activities.
• Angiopoietin-related growth factor.
• Free testosterone.
• Insulin.
IR was calculated by homeostasis model assessment (HOMA) score.
In the present work, the decreased in AGF values in the obese group may explain how AGF counteracts obesity and insulin resistance. AGF serum level was significantly lower, while insulin and HOMA-IR index were significantly higher in the obese than the overweight group. Furthermore, anthropometric indices (BMI, WC, HC, and WHR) correlate negatively with AGF serum levels in obese group.
Several studies reported that AGF suppresses gluconeogenesis in a concentration dependent manner through reduced expression of a key gluconeogenic enzyme, glucose-6-phosphatase, resulting from the activation of PI3-K / AKT/ FOXO1 signaling cascade. Other studies suggested also a direct effect in improving insulin signaling. Present data demonstrate significant decrease in serum AGF levels in the obese group, suggesting over expression of glucose-6-phosphatase in the liver which is sufficient to perturb whole glucose and lipid homeostasis.
Postprandial glucose and lipids (cholesterol, TG and LDL) were significantly increased in the obese group, as compared to the normal group. Moreover, significant negative correlation were detected between AGF and both total cholesterol and TG in the total sample.
We can say that the high TG levels detected in the present study obese group who showed lower AGF levels may suggest that one mechanism whereby AGF affect insulin sensitivity is the inhibition of abnormal lipid stores in insulin target tissues, which results in insulin resistance. This was proved by other studies.
Thus, the present work and the related studies may suggest a role for AGF in switching from glucose to fatty acid metabolism through inhibition of gluconeogenesis and also through stimulation of genes for fat burning (PPARs) and also inhibition of lipogenesis (MAPK).
We can say that AGF agonist could be expected to result in improvement of hepatic glucose metabolism, insulin resistance and competing obesity.
Furthermore, low androgen levels may be the precursor of IR. It was found that hepatic androgen receptor may play a vital role in preventing the development of insulin resistance which is considered as a predisposing factor of obesity. Testosterone inhibits LPL (enzyme responsible for accumulation of TG in the fat cells), so low testosterone has the opposite effect.
In the present work, free testosterone was significantly lower in both the overweight and the obese groups as compared to the normal group, and the anthropometric measurements (BMI, WHR) were inversely correlated with free testosterone. In addition, significant negative correlations were detected between free testosterone, cholesterol, and TG, LDL and cholesterol / HDL ratio.
Prospective studies have confirmed that lower endogenous androgens predict central obesity. Visceral fat depot has a high metabolic activity with a high turnover of TG producing large amounts of free fatty acids (FFA) to the liver leading to a disturbance in glucose and lipid metabolism. High levels of FFA may reduce insulin clearance leading to hyperinsulinemia, which may further enhance hepatic gluconeogenesis and may reduce glucose uptake by muscles resulting in peripheral insulin resistance.
The data in the present study revealed higher insulin and HOMA- IR in the obese group in which free testosterone and AGF levels were significantly lower. However, no correlations could be detected between them.
Further study in large sample is necessary to better elucidate the potential relationships between sex hormones and AGF in obesity and obesity related insulin resistance.