A preprandial and postprandial plasma levels of ghrelin hormone in lean, overweight and obese Saudi females

Maha H. Daghestani

doi:10.1016/j.jksus.2009.05.001

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Original Article

21 (

); 119-124

doi:

10.1016/j.jksus.2009.05.001

A preprandial and postprandial plasma levels of ghrelin hormone in lean, overweight and obese Saudi females

Maha H. Daghestani

Zoology Department, College of Science, Section of Science and Medical Studies, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia

Received: 2009-2-24, Accepted: 2009-5-20, Published: 2009-07-01

Disclaimer:
This article was originally published by Elsevier and was migrated to Scientific Scholar after the change of Publisher.

Abstract

Ghrelin is a novel gastrointestinal peptide hormone isolated from human and rat stomach. Ghrelin administration stimulates growth hormone secretion but also causes weight gain by increasing food intake and reducing fat utilization in rodents. This study aims to determine the plasma level of ghrelin under basal condition and in response to a standard meal and to elucidate the relationship between this peptide and anthropometric measures. Body mass index (BMI), anthropometric measurements were calculated and plasma ghrelin concentrations were determined in 122 obese, overweight and lean Saudi females before and an hour after breakfast. Fasting ghrelin was significantly higher in lean than in obese and overweight subjects and fall after eating in the lean group. There was slight insignificant reduction in circulating ghrelin of the obese and overweight groups. Ghrelin levels were negatively correlated with BMI in obese, overweight and lean subjects. Obese subjects do not exhibit the decline in plasma ghrelin seen after a meal in the lean; the lack of suppression following a meal in obese subjects could lead to increased food consumption and suggest that ghrelin may be involved in the pathphysiology of obesity.

Keywords

Ghrelin hormone

Obesity

Body mass index

Anthropometric measurements

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1 Introduction

Obesity is a major global epidemic problem (Bray, 2005). It concerns about 35.5% of Saudi adult population (Al-Nozha et al., 2005; Al-Othaimeen et al., 2007). Obesity is a multifactorial disease with genetic, endocrinal and environmental origins (Bouchard, 1994; Daghestani et al., 2007), resulting from an imbalance between energy intake and expenditure.

Ghrelin, the endogenous ligand for the growth hormone secretagogue receptor (GHSR) (Sun et al., 2007), is a 28-amino-acid peptide that is secreted primarily by cells in the oxyntic glands of the stomach as well as in the intestine (Date et al., 2000). It has been reported to have endocrine and nonendocrine actions (Abiko et al., 2005; Allison et al., 2005; Leite-Moreira et al., 2008; Taub, 2008 ). Ghrelin is a circulating orexigen (Pazos et al., 2008), and food intake increases after administration of exogenous ghrelin in both rodents and humans (Tschop et al., 2000; Wren et al., 2001 ). Consistent with a physiological role for ghrelin in feeding behavior, the administration of antighrelin antibodies or GH secretagogue receptor antagonists reduces food intake (Nakazato et al., 2001). Changes in plasma ghrelin levels might therefore produce important differences in food intake and energy balance and play a significant role in the pathogenesis of obesity (Soriano-Guillén et al., 2004). Ghrelin levels are reported to be increased in Anorexia nervosa (Otto et al., 2001) and after fasting (Muller et al., 2002), whereas in obese patients (Tschop et al., 2001a ) and after feeding they are decreased (Tschöp et al., 2001b; English et al., 2002 ). These data suggest that ghrelin plays an important endocrine role linking the peripheral mechanisms regulating caloric intake with hypothalamic centers that control energy balance (Muccioli et al., 2002).

This study aims to determine the plasma level of ghrelin under basal condition and in response to a standard meal and to elucidate the relationship between this peptide and anthropometric measures in Saudi females.

2 Material and methods

2.1

2.1 Subjects

A total of 122 Saudi females volunteers were recruited, aged 20–30 years (mean ± SEM). The subjects were divided into three groups according to their body mass index (BMI); lean (n = 60, BMI 18.5–24 kg/m²), overweight (n = 17, BMI 25–29 kg/m²) and obese (n = 45, BMI ⩾30 kg/m²). BMI for different groups was determined according to the criteria of the World Health Organization (WHO, 2000). The general characteristics of the subjects are summarized in Table 1. All subjects were healthy, free of any medication with regular menstrual cycle, and no history of gastrointestinal or endocrine disorders. Ethical approval was obtained from KFSH&RC Research Ethical committees, and written informed consent was obtained from all subjects.

Table 1 Baseline characteristics of participants.

Variables	Control lean (n = 60)	Overweight (n = 17)	P-value	Obese (n = 45)	P-value
Age (yr)	23.95 ± 0.60	21.59 ± 0.94	NS	26.49 ± 0.96	0.03
BMI (kg/m²)	20.85 ± 0.25	27.38 ± 0.37	<.0001	35.90 ± 0.92	<.0001
Waist (cm)	66.85 ± 0.70	81.59 ± 1.82	<.0001	100.29 ± 2.14	<.0001
Hip (cm)	94.59 ± 0.91	105.29 ± 1.78	<.0001	121.96 ± 2.14	<.0001
WH ratio	0.71 ± 0.01	0.78 ± 0.01	<.0001	0.82 ± 0.01	<.0001
Fasting ghrelin (ng/ml)	0.57 ± 0.02	0.44 ± 0.02	<.0001	0.28 ± 0.01	<.0001
Postprandial ghrelin (ng/ml)	0.30 ± 0.01	0.41 ± 0.02	<.001	0.27 ± 0.01	0.02

Note: values are expressed as mean ± SE, BMI (body mass index), WH ratio (waist hip ratio), NS (nonsignificant). P-level by Student’s t-test.

2.2

2.2 Protocol

After an overnight fasting (12 h) 5 ml venous blood samples were obtained from all subjects in the morning between 08.00 h and 09.00 h by venipuncture. Following fast blood sample collection, subjects consumed a standard mixed breakfast of about 527 kcal during 15 min. The meal consisted of 50 g white bread, 33 g black bread, 18 g margarine, 30 g cheese, 9 g jam and 200 ml of 0.5% fat milk (24.1% fat, 54.4% carbohydrate, 21.5% protein). Blood samples were collected 60 min after the meal ingestion. The samples were collected into chilled tubes containing 1.2 mg EDTA and aprotinin (500 KIU/ml; Trasylol; Bayer Corp., Leverkusen, Germany) for hormone analyses. All samples were kept in an ice bath until centrifugation at 3000 rpm for 15 min at 4 °C. Plasma was isolated and stored at −80 °C until analysis.

2.3

2.3 Anthropometric measurements

Measurements were performed after an overnight fast. Body mass was measured on calibrated balances or electronic scales to the nearest 0.1 kg. Body height was measured to the nearest centimetre. BMI was calculated as body mass (kilograms) divided by body height (meters) squared. Using a tape measure, with the subject standing, the waist was measured as the narrowest circumference between the lower costal margin and the iliac crest. The hip was the maximum circumference at the level of the femoral trochanters.

2.4

2.4 Analytical method

Serum ghrelin levels were measured in duplicate using a commercial ghrelin (human) enzyme immunoassay kit (EIA) from (Phoenix Pharma-ceuticals, INc (Belmont, CA)) with a lower limit of detection of 0.06 ng/ml.

2.5

2.5 Statistical analysis

The descriptive characteristics of the group variables were expressed as mean ± SEM. The comparisons among overweight, obese and their lean matched control were done using the independent t-test with respect to all variables. Pearson Correlation Coefficient was used to find the correlation between ghrelin and other studied variables. Significance was declared when P-values are less than 0.05. All statistical analyses were performed using the StatView program for Windows (version 8.0; SAS Institute, Inc., Cary, NC).

3 Results

The mean age, BMI, anthropometric, mean ghrelin concentrations of the groups are shown in Table 1.

As presented in Table 1 Student’s t-test was applied and significant differences were found in the waist, hip and waist/hip ratio among overweight and obese subjects compared with lean control group.

The fasting ghrelin level was generally decreasing with increasing body weight, it was evident that the levels were remarkably higher among lean females if they were compared with the overweight and obese groups, these differences were statistically significant P < 0.001 (Table 1). The mean fasting serum ghrelin concentration in these three groups was negatively correlated with BMI (Table 2). In lean group ghrelin levels negatively correlated with waist and hip (Table 2). In overweight group the negative correlation was found only between ghrelin levels and both BMI and hip (Table 2). In obese group ghrelin levels negatively correlated with waist, hip (Table 2). Ghrelin concentration was declined after the meal in lean control. Meanwhile slight reduction in overweight and obese groups was observed. These differences were statistically significant (P < 0.001 and P < 0.05, respectively).

Table 2 Correlation between fasting ghrelin and different parameters in lean, overweight and obese groups.

Variables	Lean control group		Overweight group		Obese group
Variables	r	P	r	P	r	P
Age (yr)	−0.310	0.018	−0.032	0.904	−0.0159	0.9175
BMI (kg/m²)	−0.616	<.0001	−0.583	0.014	−0.8102	<.0001
Waist (cm)	−0.490	<.0001	−0.353	0.165	−0.692	<.0001
Hip (cm)	−0.492	<.0001	−0.549	0.022	−0.718	<.0001
WH ratio	−0.041	0.758	0.0204	0.938	−0.212	0.162

4 Discussion

Several observations from rodent studies support the hypothesis that ghrelin is a physiological meal initiator. First, ghrelin is synthesized primarily by the stomach (Kojima et al., 1999), an organ that is well positioned to sense short-term fluxes in energy balance. Second, despite being produced peripherally, ghrelin acts centrally to stimulate food intake (Wren et al., 2000). Third, ghrelin affects feeding rapidly, increasing both food intake (Asakawa et al., 2001) and gastric acid secretion within 20 min of intraperitoneal injection (Masuda et al., 2000). Fourth, exogenous ghrelin triggers eating in rodents during the day (Wren et al., 2000; Asakawa et al., 2001; Nakazato et al., 2001 ), a time when food intake is usually nominal. Finally, ghrelin activates hypothalamic neuropeptide Y/Agouti-related peptide neurons (NPY/AGRP) and increases AGRPgene expression. AGRP has been implicated as a central mediator of meal initiation because mRNA levels in the hypothalamus rise shortly before the onset of maximal daily food intake in ad libitum–fed rats, whereas levels of other neuropeptides involved in energy balance are stable throughout the day (Watson et al., 1999). In this study, we measured the plasma ghrelin levels in 122 Saudi females and investigated the associated factors. Our data show that, in lean subjects fasting plasma ghrelin levels were shown to rise nearly twofold before meal and fall to trough levels within 1 h after eating. The finding that preprandial rise and postprandial fall in plasma ghrelin levels has been previously demonstrated (Shiiya et al., 2002; Vicennati et al., 2007), and supports the hypothesis that ghrelin plays a physiological role in meal initiation in humans.

In this study, BMI were inversely correlated with fasting plasma ghrelin levels. This confirmed the view that ghrelin is closely associated with obesity. Ghrelin has been considered as a cause of obesity in some studies, on account of the fact that ghrelin has orexigenic effects in both rats and humans (Haqq et al., 2003; Tang-Christensen et al., 2004). However, the results of most studies in humans, similar to ours, have demonstrated that ghrelin levels are negatively correlated with BMI (Tritos et al., 2003; Baldelli et al., 2006; Zou et al., 2008 ).

Several studies have reported that fasting plasma ghrelin is reduced in obese subjects as compared to lean controls (Hansen et al., 2002; Broglio et al., 2004; Suematsu et al., 2005 ). Our data show that serum ghrelin levels are significantly decreased in obese and overweight subjects and remain decreased after meal as compared with BMI-matched controls. The absence of this fall in obese and overweight subjects could demonstrate impaired suppression of the drive to eat following a meal in obese subjects leading to increased food consumption and weight gain.

Currently factors thought to inhibit ghrelin secretion include leptin, interleukin-1β, GH and high fat diet (Shintani et al., 2001; Lee et al., 2002). Stimulatory factors appear to be fasting and a low protein diet These factors may explain why ghrelin is suppressed in obese subjects but do not explain the dynamic response of ghrelin to eating, why concentration of peptide that stimulates gastric emptying (Vicennati et al., 2007) fall after food ingestion or why these responses are altered in obese individuals. Zou et al. (2008) speculate that the lower ghrelin levels in obesity are part of negative feedback to inhibit appetite and body weight, but not the primary cause of obesity (McLaughlin et al., 2004). This is also supported by the fact that circulating ghrelin levels increase in anorexia and cachexia (Misra et al., 2005; Janas-Kozik et al., 2007). However, animals without ghrelin do not have significantly altered body weight or food intake when compared with their wild-type littermates (Sun et al., 2003; Wortley et al., 2004). This suggests that it is a part of a reversible feedback mechanism, but not a determinant factor (Zou et al., 2008).

In conclusion, there are profound differences between ghrelin baseline concentration and dynamic responses to food intake in lean and obese subjects. The fall in plasma ghrelin concentration in lean subjects may represent suppression of a hunger signal. The lack of similar fall in obese subjects may indicate that ghrelin secretion is already maximally suppressed in this group, or a persistent orexigenic drive, failing to respond to food intake, that predisposes to obesity. Further studies are required to investigate the effect and the mechanism of ghrelin deficiency in individuals with obesity.

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Introduction

Material and methods

Subjects
Protocol
Anthropometric measurements
Analytical method
Statistical analysis

Results

Discussion

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[1] Abiko Y., Suzuki H., Masaoka T., Nomura S., Kurabayashi K., Hosoda H., Kangawa K., Hibi T., . Enhanced plasma ghrelin levels in Helicobacter pylori-colonized, interleukin-1-receptor type 1 homozygous knockout (IL-1R1−/−) mice. World J. Gastroenterol.. 2005;11:4148-4153.
[Google Scholar]

[2] Allison K.C., Ahima R.S., O’Reardon J.P., Dinges D.F., Sharma V., Cummings D.E., Heo M., Martino N.S., Stunkard A.J., . Neuroendocrine profiles associated with energy intake, sleep, and stress in the night eating syndrome. J. Clin. Endocrinol. Metab.. 2005;90:6214-6217.
[Google Scholar]

[3] Al-Nozha M.M., Al-Maatouq M.A., Al-Mazrou Y.Y., Al-Harthi S.S., Arafah M.R., Khalil M.Z., . Obesity in Saudi Arabia. Saudi Med. J.. 2005;26:824-829.
[Google Scholar]

[4] Al-Othaimeen A.I., Al-Nozha M., Osman A.K., . Obesity: an emerging problem in Saudi Arabia. Analysis of data from the National Nutrition Survey. Eastern Mediterranean Health J.. 2007;13:441-448.
[Google Scholar]

[5] Asakawa A., Inui A., Kaga T., Yuzuriha H., Nagata T., Ueno N., Makino S., Fujimiya M., Niijima A., Fujino M.A., Kasuga M., . Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology. 2001;120:337-345.
[Google Scholar]

[6] Baldelli R., Bellone S., Castellino N., Petri A., Rapa A., Vivenza D., Bellone J., Broglio F., Ghigo E., Bona G., . Oral glucose load inhibits circulating ghrelin levels to the same extent in normal and obese children. Clin. Endocrinol.. 2006;64:255-259.
[Google Scholar]

[7] Bouchard C., . Genetics of obesity: overview and research directions. In: Bouchard C., ed. The Genetics of Obesity. Boca Raton, FL: CRC Press; 1994. p. :223-233.
[Google Scholar]

[8] Bray G.A., . Epidemiology, risks and pathogenesis of obesity. Meat Sci.. 2005;71:2-7.
[Google Scholar]

[9] Broglio F., Gianotti L., Destefanis S., Fassino S., Abbate Daga G., Mondelli V., Lanfranco F., Gottero C., Gauna C., Hofland L., Van der Lely A.J., Ghigo E., . The endocrine response to acute ghrelin administration is blunted in patients with anorexia nervosa, a ghrelin hypersecretory state. Clin. Endocrinol.. 2004;60:592-599.
[Google Scholar]

[10] Daghestani M.H., Ozand P.T., Al-Himadi A.R., Al-Odaib A.N., . Hormonal levels of leptin, insulin, ghrelin, and neuropeptide Y in lean, overweight, and obese Saudi females. Saudi Med. J.. 2007;8:1191-1197.
[Google Scholar]

[11] Date Y., Kojima M., Hosoda H., Sawaguchi A., Mondal M.S., Suganuma T., Matsukura S., Kangawa K., Nakazato M., . Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology. 2000;141:4255-4261.
[Google Scholar]

[12] English P.J., Ghatei M.A., Malik I.A., Bloom S.R., Wilding J.P., . Food fails to suppress ghrelin levels in obese humans. J. Clin. End. Metab.. 2002;87:2984-2987.
[Google Scholar]

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