الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
The incidence of obesity and its related insulin resistance is increasing dramatically in virtually all societies of the world, with important pathological consequences such as type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD).T2DM is increasing at an alarming rate in both developed and developing countries, associated with a combined health and economic burden worldwide.
The association between obesity and insulin resistance is likely a cause-and-effect relationship since human and animal studies indicate that weight loss/gain correlates closely with increasing/decreasing insulin sensitivity, respectively.
The metabolic syndrome refers to a cluster of several cardio-metabolic risk factors, including central obesity, hyperglycemia, dyslipidemia (elevated triglycerides, low levels of high density lipoprotein cholesterol) and elevated blood pressure, all of which have been linked to insulin resistance.
A fundamental diagnostic challenge is to identify among the obese population individuals whose obesity causes more metabolic stress and who, consequently, are more likely to develop T2DM and cardiovascular diseases. This suggests that the fat mass per se may not be the best predictor and that a marker that could indicate the metabolic stress posed by a specific degree of obesity may be particularly useful. However, there are no good early predictor markers of the metabolic risk posed by obesity. Thus, new biomarkers and therapeutic targets useful for diagnostic and prevention purposes, are urgently needed.
Several reports suggest that stress-mediated activation of the hypothalamic pituitary axis (HPA) is frequently accompanied by increased plasma levels of arginine vasopressin (AVP), which is an amplifier of HPA axis along with corticotropin releasing hormone (CRH). Since obesity represents a chronic stressor, AVP is suggested to have a role in the pathogenesis of insulin resistance and metabolic syndrome.
Arginine vasopressin (AVP) is an unstable molecule both in vivo and ex vivo, is cleared rapidly from plasma, and is largely attached to platelets in the circulation. Copeptin is a cleavage product of the C-terminal part of the AVP precursor that is produced in equimolar amounts with AVP, a process similar to the generation of insulin and C peptide. In contrast to AVP, copeptin is stable, has a long half-life, and is not bound to platelets. Therefore, copeptin is found in considerably higher concentrations in plasma than AVP.
Previous findings indicate several links between the AVP system and components of the MetS. A cross-sectional association was found between plasma copeptin and MetS criteria e.g. high waist circumference, high systolic blood pressure (SBP), hyperglycemia and dyslipidemia.
It can be, therefore hypothesized that plasma copeptin would be associated with measures of obesity-induced insulin resistance and metabolic syndrome.
Accumulating evidence suggests that lipid metabolism is as important, if not more, to diabetes as carbohydrate metabolism. Lipogenesis occurs either as a consequence of re-esterification of FFA with glycerol or de novo synthesis of TAGs. De novo lipogenesis may account for up to 20% of lipid turnover within adipose tissue. During de novo lipogenesis, acetyl CoA is carboxylated to malonyl-CoA by acetyl CoA carboxylase (ACC) which is subsequently converted by a multi-step reaction to palmitate by FASN.
It has been suggested that when FASN is excessively accumulated beyond the metabolic needs of the cellular system as under conditions of insulin resistance, FASN can be actively extruded from the metabolically stressed cells e.g. tumor cells.
It has been reported that AMP kinase (AMPK)-sensed cellular energy state actively regulates the release of extracellular FASN in human breast cancer cells. These results support the hypothesis that FASN release is an active and controlled process regulated and facilitated by AMPK activation in the context of energy depletion.
Therefore, FASN might be a potential marker of metabolic stress and insulin resistance.
The aim of the present study is designed to evaluate the use of Plasma Carboxy-Terminal Provasopressin (Copeptin) and Extracellular Fatty Acid Synthase (FASN) as possible novel biomarkers associated with measures of insulin resistance and presence of metabolic syndrome in obese individuals.
In order to achieve this goal, 60 subjects were evaluated and divided into three groups, the first group (group 1) included twenty obese adult individuals with metabolic syndrome. They were assessed to have metabolic syndrome according to the criteria of the National Heart, Lung, and Blood Institute (NHLBI) and the American Heart Association (AHA), and were chosen from those attending the Alexandria Main University Hospital. Group (II): included twenty age-matched obese adults without metabolic syndrome. Group (III): included twenty age-matched non obese healthy adult volunteers.
Following proper selection of patients and control subjects, the following laboratory tests were performed for all of them:
1. Enzymatic colorimetric determination of plasma glucose, triacylglycerol and total cholesterol.
2. Colorimetric determination of plasma HDL.
3. Measurement of plasma insulin by enzyme-linked immunosorbant assay (ELISA).
4. Measurement of plasma copeptin by enzyme-linked immunosorbant assay (ELISA).
5. Measurement of plasma fatty acid synthase by enzyme-linked immunosorbant assay (ELISA).
The present study showed
• A statistically significant elevation of both copeptin and FASN levels in group I (obese with MetS) compared to the other two groups.
• There were strong positive correlations between each of the two markers and criteria of IR (FPG, fasting insulin, HOMA-IR) independently.
• There were strong positive correlations between each of the two markers and most of the criteria of MetS independently.
• A statistically significant elevation of FASN levels in subjects of group II (obese without MetS) compared to group III (controls).
• There was no statistically significant elevation of copeptin levels in subjects of group II (obese without MetS) compared to group III (controls).
•No significant differences were found between males and females all over the quartiles of both copeptin and FASN.