الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Obesity is a public health concern that has raised concern worldwide. In 2014, WHO estimated that more than 1.5 billion adults globally were overweight, of these 600 million were obese. A recent report by the WHO indicated that 39% of adults aged 18 years and over were overweight in 2014, and 13% were obese. The problem of obesity in Egypt is reaching an epidemic level. Data from the Egypt Demographic and Health Survey 2014 indicated that when excluding those who were pregnant or less than two months postpartum, the mean BMI of ever married women age 15-59 was 29.4 kg/m². The majority of women had a BMI of 25.0 kg/m2 or higher, and were considered overweight (37 percent) or obese (48 percent). The etiology of obesity is multifactorial, involving complex interactions among the genetic background, hormones and different social and environmental factors, such as sedentary lifestyle and unhealthy dietary habits.
Ghrelin is a neuroendocrine hormone secreted mainly by the stomach. Ghrelin is made of 28 amino acids and exists in two major forms: n-octanoyl modified ghrelin (acylated ghrelin) and des-acyl ghrelin. It acts as a ligand for the growth hormone (GH) secretagogue receptor and plays a major role in appetite stimulation. Apart from influencing the release of growth hormone from pituitary, it also functions on gastrointestinal system, cardiovascular system, energy balance and metabolism. Studies have showed that ghrelin levels in the circulation were mostly changed in relation to the nutritional intake, thus suggesting a primary role in the regulation of food intake and absorption.
The characterization of the gene encoding ghrelin and its overall genomic structure has made it possible for genomic screening of the ghrelin gene. Mutations in the ghrelin gene could potentially cause a defective or inactive ghrelin and alter growth hormone secretion and energy balance. Two ghrelin mutations were detected and investigated for their relation to ghrelin hormone concentration and obesity. One ghrelin mutation was detected at amino acid position 51 of the preproghrelin gene resulting from a single base substitution Gl52A, with glutamine (Gln) replacing arginine (Arg) at codon 28 of mature ghrelin. The second mutation, Leu72Met of the preproghrelin gene, where a cytosine C to adenine transition occurs at base 408 resulting in a substitution of leucine to methionine in position 72 (Leu72Met).
The current study was conducted to determine the relationship between ghrelin hormone blood level, body mass index (BMI), and other anthropometric measurements; it also attempts to explore the relation between the ghrelin hormone blood level and food intake. Furthermore the current study aimed to determine the genetic mutations of the ghrelin hormone gene and their relation to the ghrelin hormone’s blood level and obesity in adults.
Regarding the relation between ghrelin hormone level and BMI, in the present study the mean and median fasting ghrelin hormone levels were significantly lower in obese individuals compared to normal weight controls. The median ghrelin hormone level among obese males was (7.7pg/ml) compared to (27.8 pg/ml among normal weight group (U=5.7, P=0.001). Among obese females, the median hormone level was (10.1 pg/ml) compared to (27.4 pg/ml) among normal weight group (U=8.1, P=0.001). Moreover the median ghrelin hormone level showed a statistical significant difference among the three classes of obesity and the normal weight group (13.4, 9.8, 8.0, and 27.4pg/ml respectively). (HP= 52.6,
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P=0.001), furthermore the median ghrelin hormone level was lower between obesity group class II compared to class I obese group however, in the class III obese group the median ghrelin hormone level was higher than the other two obesity classes but the difference was not statistically significantly.
Regarding waist circumference as a predictor for central obesity a negative relation was detected between ghrelin hormone level and waist circumference according to a hierarchical multiple regression analysis conducted in the present study. (b=-0.015, SE=0.002, P=0.0001).
Several factors may affect plasma ghrelin levels including age, sex, smoking habits, life style and dietary intake, As regard the age and sex no significant difference in the ghrelin hormone level was detected between different age categories whether among obese or normal weight individuals. (P=0.75, 0.713) respectively. Similarly, no statistical significant difference was detected in the hormone level between males and females either obese or normal weight individuals. (Mann-Whitney P=0.07 and P=0.69 respectively). As regard smoking habits no significant difference of the median ghrelin hormone level among smokers and nonsmokers in both groups (P= 0.849, P=0.640, respectively). However as regard playing sports the median ghrelin hormone level among individuals who practiced sports was higher than among individuals who didn’t practice sports in both obese and normal weight groups but the difference was not statistically significant (P=0.682, P=0.894 respectively).
Regarding food intake the present study indicated that meals and snacks frequency, daily consumption of all macronutrients and the total energy consumption among obese males and females were significantly higher compared to the corresponding normal weight group. It also exceeded the recommended daily caloric intake. Additionally, among the normal weight group, the lowest hormone level was present in individuals who preferred fat-rich foods; however, the difference was not statistically significant (p>0.05). upon conducting a multiple regression analysis, the percent of energy intake from fat – explained 1.3% of the negative variation in ghrelin hormone levels (b=-0.124, SE=0.055, P=0.026). Furthermore the regression analysis detected the following negative correlation between ghrelin hormone level and the following parameters: upon conducting a multiple regression analysis, the percent of energy intake from fat – explained 1.3% of the negative variation in ghrelin hormone levels (b=-0.124, SE=0.055, P=0.026). Furthermore the regression analysis detected the following negative correlation between ghrelin hormone level and the following parameters: BMI (rs=-0.55), TG (rs=-0.25), LDL (rs=-0.22), FBS (rs=-0.27), Total Eng. (rs=-0.41), post prandial blood glucose level (rs=-0.21), percent of energy from fat (rs=-0.18),and percent of energy from saturated fat (rs=-0.12). Additionally a significant weak positive correlation was detected between ghrelin hormone level and HDL (rs=+0.16), and percent of energy intake from protein (rs=+0.12).
The present study has demonstrated the existence of Arg51Gln SNPs in the current study population, although without association with obesity after conducting a logistic regression analysis. Nonetheless, the regression analysis detected a significant negative association between the ghrelin hormone level and the Arg51Gln mutation, which explains the 1.3% of variation in ghrelin hormone levels. Furthermore, the fasting and post prandial blood glucose level was higher among individuals with the Arg51Gln mutation in both
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obese and normal weight individuals compared to individuals with no Arg51Gln mutation and the difference was statistically significant among obese individuals.
Regarding the second ghrelin SNP examined in the present study is the Leu72Met there was no statistically significant difference between male and female participants in regard to the Met 72 mutation allele distribution, however, the mutation rate was significantly higher in the normal weight group compared to the obese group in both male and female participants. As regard Leu72 Met and blood sugar level, in the current study there was no statistically significant difference in the FBS between obese and normal weight individuals with the Leu72Met mutation. However, among obese individuals, fasting blood sugar (FBS) level was the lowest in individuals having Leu72Met mutation, followed by individuals with no mutation, then individuals with Arg51Gln mutation with a statistically significant difference.
from the results of the present study, it could be concluded that:
Ghrelin hormone level was significantly lower among obese individuals compared to normal weight group. Moreover the median ghrelin hormone level was lower among the three classes of obesity compared to normal weight group. Furthermore a negative relation was detected between ghrelin hormone level and waist circumference.
No statistical significant difference between ghrelin hormone level in respect to age and sex and smoking habits for both obese and normal weight individuals.
The number of meals and snacks frequency, daily consumption of all macronutrients and the total energy consumption among obese males and females were significantly higher compared to the corresponding normal weight group.
The present study has demonstrated the existence of Arg51Gln SNPs in the current study population, although without association with obesity, however the mutation had a negative association with ghrelin hormone level.
There was no statistically significant difference between male and female participants in regard to the Leu72Met mutation allele distribution, however, the mutation rate was significantly higher in the normal weight group compared to the obese group in both male and female participants.
from the results of the present study, we can recommend that: To adopt a personalized approach in prevention and management of obesity, as the etiology of obesity involves involving complex interactions among the genetic background, hormones and different social and environmental factors. Coordinate ghrelin hormone research for obesity to involve not only ghrelin but also leptin and other obesity related genes. Since obesity is a multifactorial disease, obesity research involves several health care specialists and departments including nutrition, genetics, pathology and laboratory medicine, internal medicine, surgery and more. It is recommended to develop an obesity research network to coordinate the obesity research across Alexandria University so that all researchers could benefit from their colleagues research.