Assessment of Biochemical Changes among Egyptian Women with Increased Body Weight

Mie Afify; Nervana Samy; Maha Hashim; Abd El-Maksoud; Omneya Saleh

doi:10.4172/2165-7904.1000127

ISSN: 2165-7904

Journal of Obesity & Weight Loss Therapy

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Assessment of Biochemical Changes among Egyptian Women with Increased Body Weight

*Mie Afify¹, Nervana Samy^1, Maha Hashim¹, Abd El-Maksoud¹ and Omneya Saleh²**
¹Biochemistry Department, National Research Centre, Cairo, Egypt
²Internal Medicine Department, National Research Centre, Cairo, Egypt
Corresponding Author :	Dr. Nervana Samy Professor of Biochemistry, Biochemistry Department National research Centre, Cairo, Egypt E-mail: nervana91@hotmail.com
Received March 27, 2012; Accepted April 18, 2012; Published April 22, 2012
Citation: Afify M, Samy N, Hashim M, El-Maksoud A, Saleh O (2012) Assessment of Biochemical Changes among Egyptian Women with Increased Body Weight. J Obes Wt Loss Ther 2:127. doi:10.4172/2165-7904.1000127
Copyright: ©2012 Afify M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Keywords

Ghrelin; Leptin; HOMA; Obesity

Introduction

Obesity is a condition that results from chronic disruption of energy balance; energy intake continuously exceeds energy expenditure and accumulation of body fat follows [1]. The prevalence of obesity is on the rise and the obesity pandemic is arguably amongst the most serious public health challenges in the world today. Obesity is strongly associated with type 2 diabetes mellitus, hyperlipidemia and cardiovascular disease, and provides significant contributions to ill health in both western and developing countries. Extensive research into the mechanisms of appetite regulation and energy balance has unveiled complex physiological systems behind energy homeostasis, and yielded potential targets for therapeutic intervention in the fight against obesity [2]. It has been reported that the prevalence of obesity in adults is very high in Egypt, as many as 35% of the population has a BMI over 30, particularly among women, also, the prevalence of diabetes and hypertension parallels that of obesity [3].

The hypothalamus is crucial for appetite regulation and energy homeostasis. Afferent signals from peripheral sites such as the gastrointestinal tract and adipose tissues are integrated by complex neuronal networks to produce efferent responses responsible for food intake and energy metabolism. There are numerous hypothalamic appetite regulators. Orexigenic (appetite-stimulating) compounds include neuropeptide Y (NPY), agouti-related peptide (AgRP), ghrelin, orexin and cannabinoids, and anorexigenic (appetite-suppressing) peptides include pro-opiomelanocortin (POMC) and cocaine- and amphetamine- regulated transcript (CART), thyrotropin-releasing hormone (TRH) and corticotrophin-releasing hormone (CRH) [4].

The appetite-stimulating function of ghrelin was identified secondary to its effect on growth hormone (GH) release from somatotroph cells of the anterior pituitary [5]; however, ghrelin is the first known peripheral hormone to display orexigenic effects through its action on the hypothalamic appetite-regulating pathways [6]. In addition, ghrelin is amongst the most powerful of the orexigenic peptides [7]. While most orexigenic peptides originate from the brain and are only active when injected into the brain, ghrelin is active even with peripheral administration leading to an increase in appetite in rodents and humans [8,9]. Ghrelin activates NPY/AgRP neurons of the hypothalamic arcuate nucleus (ARC) through its receptor [10]. Plasma ghrelin levels inversely correlate with body mass index (BMI). Thus, ghrelin levels are reduced in those who are obese compared to normal body weight controls [11,12]. Recent evidence suggests that diet-induced obesity causes ghrelin resistance by reducing NPY/AgRP responsiveness to plasma ghrelin and suppressing the neuroendocrine ghrelin axis, in an attempt to limit further food intake [13].

Leptin, known as the prototypical adipokine, is a 167-amino acid peptide with a four-helix bundle motif similar to that of acytokine [14]. It is produced primarily in adipose tissue but is expressed in a variety of tissues including the placenta, ovaries, mammary epithelium, bone marrow [15], and lymphoid tissues [16]. Leptin levels are pulsatile and follow a circadian rhythm, with highest levels between midnight and early morning and lowest levels in the early- to mid-afternoon. Specifically, the concentration of circulating leptin may be up to 75.6% higher during the night as compared to afternoon trough levels [17]. The pulsatile characteristics of leptin secretion are similar in obese and lean individuals, except the obese have higher pulse amplitudes [18].

Leptin regulates energy homeostasis and reproductive, neuroendocrine, immune and metabolic; its concentration reflects the amount of energy stored in body fat. Circulating leptin levels are directly proportional to the amount of body fat [19] and fluctuate with acute changes in caloric intake [20]. Leptin controls energy homeostasis and body weight primarily by activating Ob Rb in the hypothalamus [21].

The Ob Rb activate numerous JAK2/STAT3-dependent and – independent signaling pathways that act in coordination as a network to fully mediate leptin’s action. The activation of individual pathways in the leptin signaling network appears to be differentially regulated in discrete subpopulations of ObRb-expressing neurons.

These pathways are also likely to be regulated by various other hormonal, neuronal, and metabolic signals that cross-talk with leptin. Hence, it is important to fully determine whether and how positive and negative regulators of ObRb signaling, metabolic state, and/or neuronal activity regulate leptin signaling networks in a cell/tissue type-specific manner and how activation of these signaling pathways mediates leptin’s effects in humans [22].

Aim of the Work

The aim of this work is to evaluate the relationships between ghrelin and leptin with the metabolic state of overweight and obese participants among Egyptian women.

Materials and Methods

This study was conducted on 82 participants, their age ranged from 43 to 65 free from cancer or endocrine-related disease (e.g., diabetes) they were divided into three groups according to their body mass index (BMI). Group 1 (G1) with BMI less than 25 Kg/m², Group 2 (G2) with BMI between 25-30 kg/m² and Group 3 (G3) with BMI more than 30 Kg/m². BMI was calculated for all groups as body weight (kg) divided by body height squared (m²). Insulin resistance was assessed by means of the homeostasis model assessment (HOMA), which was measured by multiplying fasting serum insulin (micro-units per milliliter) and fasting plasma glucose (micromoles per liter) divided by 22.5 [23].

Methods

-Blood samples were obtained from participants in the morning after a 12-hour overnight fast. Within 1 hour of collection, samples were processed and stored at −70°C.

-Total plasma leptin concentrations were measured using a commercial RIA kit (Linco Research Inc, St Charles, MO) [19].

-Plasma glucose level was estimated by God-PAP enzymatic colorimetric method [25] using Biomerieux test kit, Cat. No.5 127.

- Serum insulin was detected by commercially available radioimmunoassay (Abbott IMx Insulin assay) which is a micro-particle Enzyme Immunoassay [MEIA] for the quantitative measurement of human insulin [26].

-Measurement of lipid profile (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglycerides) by commercial enzymatic methods (Aeroset automated analyzer, Abbott Laboratories, Abbott IL). LDL cholesterol was calculated by using Friedewald’s formula [27]

Statistical Analysis

Standard descriptive statistics were used to summarize the data (e.g., means and standard deviations (SD)). To assess between group differences, we used non-parametric testing (Wilcoxon–Mann– Whitney test). Correlation coefficients reported as Spearman rank correlations.

Results

Clinical features of the women joined this study are summarized in (Table1), by design there were statistical difference between the three groups as regard the BMI. The incidence of hypertension increased among the obese group compared to the control group.

From the (Table 2), over-weight group (G2) and obese group (G3) highly significant reductions (P<0.001) were observed in the level of ghrelin with means + SD (11.6 ± 4.1 ng/ml) and (12.9 ± 8.7 ng/ml) respectively, as compared with normal weight group (GI) (23.7 ± 9.5 ng/ml) and a significantly difference between over-weight group (G2) and obese group (G3) was observed. The level of leptin hormone in sera of over-weight group (G2) were significantly increased with a mean of (25.3 ± 11.6 ng/ml) while the level of leptin hormone in obese group (G3) found to be highly significant increased with a mean (35.8 ± 16.4 ng/ml), as compared with normal weight group (GI) (12.6 ± 8.2 ng/ml). A significant difference between over-weight group (G2) and obese group (G3) was observed.

Table 3 shows the levels of blood glucose, insulin and insulin resistance in studied groups. The glucose, insulin and insulin resistance concentrations in the sera of over-weight group (G2), obese group (G3) and normal weight group (GI) showed no statistically significant difference (p>0.05) between three groups with means of (86.8 ± 13.9 mg/dl), (84.2 ± 6.2 mg/dl) & (89.3 ± 7.9 ng/ml) for glucose, (16.5 ± 5.1 μlU/ml, (18.8 ± 11.7 μlU/ml) & (17.3 ± 6.8 μlU/ml) for insulin, and (3.67 ± 1.3 μlU/ml), (4.08 ± 2.8 μlU/ml) & (3.77 ± 1.4 μlU/ml) for insulin resistance concentrations respectively.

Table 4 expresses the levels of cholesterol, HDL cholesterol, LDL cholesterol and triglyceride in all studied groups. The levels of cholesterol concentrations in the sera of studied groups showed no statistically significant difference (p>0.05) between three groups with means of (181.2 ± 17.5 mg/dl) & (179.5 ± 18.6 mg/dl) & (170.6 ± 14.5 mg/dl) respectively. Whereas, the results revealed significant decrease of HDL cholesterol level in over-weight group (G2) and obese group (G3) with a mean of (31.6 + 4.5 mg/dl) and (30.7 ± 5.9 mg/dl) respectively as compared to normal weight group (GI) (39.5 ± 3.7 mg/ dl). There was no significantly difference between over-weight group (G2) and obese group (G3).

The levels of LDL cholesterol concentration in the sera of overweight group (G2), obese group (G3) and normal weight group (GI) showed that no statistically significant difference between three groups with means (112.8 ± 12.8 mg/dl), (105 ± 18.9 mg/dl) & (108.6 ± 13.8 mg/dl) respectively

As regards to triglyceride levels there were highly significantly increased (p<0.05) in both over-weight group (G2) and obese group (G3) with means + SD of (141.9 ± 39.3 mg/dl) and (141.1 ± 57.8 mg/dl) respectively as compared with normal weight group (GI) (93.7 ± 25.6 mg/dl). No statistically difference between over-weight group (G2) and obese group (G3) was observed.

Table 5 represents the concentrations of blood urea in different examined groups. Overall, statistical analysis clarified that the blood urea concentration was increased significantly in obese group (G3) with a mean (29.1 ± 6.8 mg/dl), whereas in over-weight group (G2) a slightly increased was observed with a mean (24. 6 ± 5.5 mg/dl) as compared to normal weight group (G1) with a mean (23.9 ± 4.4 mg/dl).While as regard to serum levels of creatinine the statistical analysis revealed that no difference between over-weight group (G2) with a mean (0.77 ± 0.17 mg/dl) and normal weight group (GI) with a mean (0.75 ± 0.16mg/dl). But in case of obese group (G3) we obtained a significantly increased (0.88 ± 0.17 mg/dl),as compared with normal weight group (GI).

Table 6 and Figure 1 showed the correlation between ghrelin with the other studied parameters in the normal weight group. There was a statistically significant negative correlation between ghrelin, leptin, BMI and HOMA i.e., an increase in ghrelin level is associated with a decrease in leptin, BMI and HOMA levels. There was no statistically significant correlation between ghrelin, FBS and Insulin.

While as regards to leptin, there was a statistically significant positive correlation between leptin, Insulin, BMI and HOMA i.e. an increase in leptin is associated with an increase in Insulin, BMI and HOMA. There was no statistically significant correlation between leptin and FBS.

Table 7 and Figure 2 showed the correlation between ghrelin with the other studied parameters in the overweight group, there was a statistically significant negative (inverse) correlation between ghrelin, leptin, insulin, BMI and HOMA i.e. an increase in ghrelin is associated with a decrease in leptin, insulin, BMI and HOMA.There was no statistically significant correlation between ghrelin and FBS.

While as regards to leptin, there was a statistically significant positive (direct) correlation between Leptin, Insulin, BMI and HOMA i.e. an increase in Leptin is associated with an increase in Insulin, BMI and HOMA.There was no statistically significant correlation between Leptin and FBS.

Table 8 and Figure 3 showed the correlation between ghrelin with the other studied parameters in the obese group, there was a statistically significant negative correlation between Ghrelin, Leptin, Insulin, BMI and HOMA i.e. an increase in Ghrelin is associated with a decrease in Leptin, Insulin, BMI and HOMA.There was no statistically significant correlation between Ghrelin and FBS.While as regards to leptin, there was a statistically significant positive correlation between leptin, insulin, BMI and HOMA i.e. an increase in leptin is associated with an increase in Insulin, BMI and HOMA.There was no statistically significant correlation between leptin and FBS.

Discussion

We hypothesized that metabolic profile of overweight individuals would consist of relatively lower concentrations of fasting ghrelin and this what we found in our study comparing overweight and obese groups with normal weight control group, also, there was statistically significant negative correlation between ghrelin levels with leptin, BMI and HOMA.

Our results were in agreement with Yada et al. [28] who stated that ghrelin is important in short-term regulation of appetite and energy balance. The clear pre-prandial rise and post-prandial fall in plasma ghrelin levels support the hypothesis that ghrelin acts as an initiator signal for meal consumption in humans. The pre-prandial increase of ghrelin levels was found to initiate meal consumption voluntarily, without time- or food-related cues [29], while the post-prandial ghrelin suppression is proportional to the ingested calorie load [30]. Ghrelin also appears to be involved in the regulation of long-term energy homeostasis. Ghrelin shows orexigenic effect through its action on the hypothalamic appetite-regulating pathways, while in the periphery ghrelin increases adipose tissue accumulation and has a diabetogenic

Circulating ghrelin induces abdominal obesity, independently of its central orexigenic activity, via GHS-R-dependent lipid retention [32]. In agreement with our results Williams et al. [12] stated that ghrelin levels inversely correlate with body mass index (BMI). Thus, ghrelin levels are reduced in those who are obese compared to normal body weight controls. Evidence suggests that diet-induced obesity causes ghrelin resistance by reducing NPY/AgRP responsiveness to plasma ghrelin and suppressing the neuroendocrine ghrelin axis, in an attempt to limit further food intake [13]. Ghrelin levels have been shown to negatively correlate with factors which are raised in obesity namely, percentage body fat, insulin and leptin levels [11]. In one study ghrelin levels were not related to fat mass or intra-abdominal fat con- tent, but showed strong negative correlation with insulin levels and insulin resistance [33]. However in an MRI study of non-obese and obese adults, ghrelin was negatively correlated with visceral adiposity, fasting insulin, and homeostasis model insulin resistance index. Visceral adiposity showed stronger inverse correlation with ghrelin than subcutaneous fat possibly through hyperinsulinemia, as the negative correlations with insulin resistance were even stronger [34]. Abnormal glucose homeostasis inversely correlated with, and was found to be an independent determinant of, plasma ghrelin levels in obese children and adolescents [35].

Our results showed that higher concentrations of fasting leptin were found in overweight and obese groups compared with normal weight control group; also, there was statistically significant positive correlation between leptin, insulin, BMI and HOMA.

These results were in agreement with Considine et al. [36] who declared that most obese individuals have higher leptin levels than lean individuals and are resistant or tolerant to the effects of leptin. Leptin resistance was first thought to be due to mutations of the leptin receptor and other rare monogenic obesity syndromes. Mutations of other genes downstream of leptin, including POMC and MC4R, also result in an obese phenotype with associated neuroendocrine dysfunction [37]. However, only a few cases of human obesity are due to monogenic syndromes; instead, most instances appear to be multifactorial [38]. First of all, leptin transport across the blood–brain barrier is impaired in obesity. This is partially due to saturation of the transporter by hyperleptinemia, which is associated with obesity, and subsequent decrease in transport activity [39]. Targeting these mechanisms of leptin resistance will be important in the treatment for obesity and has led to development of insulin sensitizers, such as the chemical chaperones [40].

In a study done by Remsberg et al. [41], Comparable associations were noted with leptin and most measures of body composition, suggesting that leptin levels reflect total body fat and are less affected by fat distribution. Their results parallel those reported by other investigators in which leptin levels exhibit relatively stable associations across differing types of localized fat deposits [42]. Reports in the literature differ, however, on these relationships, and these associations may reflect the varying groups studied. For example, associations between leptin, body composition, and fat distribution tend to be stronger among men and weaker in the obese. Their findings suggest that subcutaneous or white adipose tissue in the abdominal region may be the best predictor of circulating leptin [43].

Mueller et al. [44] suggested that insulin has been shown to influence circulating leptin concentrations. Specifically, insulin increases leptin concentrations in rodents, both in cultured adipocytes as well as in vivo [45]. These associations have also been found in humans, at the level of the adipocyte and in the peripheral circulation wherein experimental hyperinsulinemia using clamp techniques results in increased leptin concentrations [46]. The relationship between leptin or ghrelin and insulin is potentially more complex because of the possibility of insulin resistance; where in comparable concentrations in obese individuals would not have the same effect as in leaner persons [47].

Conclusion

Our results suggest coordinated roles of ghrelin and leptin in the modulation of the obesity and these markers can be of value in assessment of treatment of such cases.