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 Table of Contents  
ORIGINAL ARTICLE
Year : 2014  |  Volume : 42  |  Issue : 1  |  Page : 1-5

Circulating obestatin level in diabetic and obese rats


Department of Physiology, Faculty of Medicine, Tanta University, Tanta, Egypt

Date of Submission06-Oct-2013
Date of Acceptance22-Nov-2013
Date of Web Publication7-Apr-2014

Correspondence Address:
Nermin M Madi
1 El Fateh street, Tanta 31528
Egypt
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DOI: 10.4103/1110-1415.130069

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  Abstract 

Background
Obestatin has been discovered as a product of the ghrelin gene. Its physiological actions are still a matter of debate. It is likely to be involved in the control of adipocyte function. It has been already shown that obestatin secretion is negatively modulated by food intake.
Aim
In this study, we investigated plasma obestatin level in diabetic and obese rats and studied the correlation of this hormone with glucose, homeostasis model assessment of insulin resistance, BMI, triglycerides, and total cholesterol in these two metabolic disorders.
Materials and methods
A total of 30 male albino rats were divided into three groups: the control group, the diabetic group, and the obese group. Plasma obestatin levels were measured and plasma glucose, insulin, triglyceride, total cholesterol, and BMI were also evaluated.
Results
Diabetic rats showed significant increase in all studied parameters except plasma obestatin, insulin, and BMI, which showed significant decrease as compared with the control group. However, the results of obese rats showed significant increase in all studied parameters except plasma obestatin, which showed significant decrease compared with either control or diabetic rats, but plasma glucose was significantly decreased as compared with diabetic rats only and homeostasis model assessment of insulin resistance was significantly increased as compared with control rats. The results revealed that plasma obestatin was negatively correlated with all studied parameters in both diabetic and obese rats and positively correlated with insulin in diabetic rats, whereas it had insignificant correlation with BMI in diabetic rats and with insulin in the obese group.
Conclusion
The decrease in obestatin levels was associated with metabolic disorders and this may contribute, in part, to the pathophysiology of diabetes and obesity.

Keywords: Body mass index, diabetes, homeostasis model assessment of insulin resistance, obesity, obestatin


How to cite this article:
Abou Fard GM, Madi NM, Abo Zade AA. Circulating obestatin level in diabetic and obese rats. Tanta Med J 2014;42:1-5

How to cite this URL:
Abou Fard GM, Madi NM, Abo Zade AA. Circulating obestatin level in diabetic and obese rats. Tanta Med J [serial online] 2014 [cited 2017 Dec 12];42:1-5. Available from: http://www.tdj.eg.net/text.asp?2014/42/1/1/130069


  Introduction Top


Obestatin, a 23-amino acid peptide, is a hormone that is encoded by a convertase. It was first isolated from rat stomach [1]. It is present not only in the gastrointestinal tract, but also in the spleen, mammary gland, breast milk, and plasma [2].

The biological activity of obestatin depends on the amidation at its carboxyl terminus. Originally, obestatin was proposed as a ligand of GPR39, an orphan receptor belonging to the ghrelin receptor family [3].

Obestatin seems to function as part of a complex gut-brain network where hormones and substances from the stomach and intestine signal the brain about satiety or hunger [4]. In contrast to ghrelin, which causes hyperphagia and obesity in rats [5], obestatin appears to act as an anorexic hormone, decreasing food intake, slowing gastric emptying and jejunal motility, and reducing body weight gain in rodents [6]. Further studies have shown that obestatin is also involved in improving memory, regulating sleep, affecting cell proliferation, increasing the secretion of pancreatic juice enzymes, and inhibiting glucose-induced insulin secretion [7]. Chanoine et al. [8] demonstrated the presence of obestatin in perinatal rat pancreas, and its levels have been found to positively correlate with insulin concentrations in the postnatal pancreas.

There is currently little information on the regulation of ghrelin and obestatin secretion, the pathways through which they mediate their effects, and their physiological or pathophysiological roles [9]. In addition, obestatin has not yet been tested in animal models of obesity and diabetes, and it is not known whether it affects glucose and lipid metabolism [1].

To shed light on the putative role of obestatin in diabetes and obesity, we measured the circulating blood levels of obestatin in a group of diabetic rats and also in a group of obese rats and compared them with controls.

We also investigated the relationship between obestatin and BMI, glucose, insulin, triglycerides (TG), and total cholesterol (TC) in both diabetic and obese groups.


  Materials and methods Top


Animals

For all experiments, male albino rats weighing 200-230 g were used. Animals were fed on standard rodent diet (except the obesity group, which received the food regimen for induction of obesity).

Experimental protocol

The animals were divided into three main groups, each consisting of 10 animals. Group I was the control group. In group II (the diabetic group), diabetes was induced by single intraperitoneal injection of streptozotocin at a dose of 60 mg/kg body weight and blood samples were analyzed for blood glucose level; the animals were considered to be diabetic when the blood glucose level became greater than 200 mg (>11.1 mmol/l) [10]. In group III (the obese group), obesity was induced by feeding a diet composed of 70% fat, 20% carbohydrates, and 10% protein [11]. Samples were collected from the animals whose weight exceeded 280 g.

Blood sampling and determination

Rats were anesthetized with an intraperitoneal injection of sodium pentobarbital. Thereafter, blood samples were collected in cooled polypropylene tubes containing EDTA-2Na (1 mg/ml), centrifuged for 15 min, and then plasma samples were stored until assayed for the determination of obestatin as described by Maier et al. [12]. Plasma glucose was determined by the hexokinase enzymatic method [13], plasma insulin level was determined by the method described by Chevenne et al. [14], TG levels were measured according to the method described by Bucolo et al. [15], and TC was measured by the enzymatic colorimetric determination method [16].

The homeostasis model assessment of insulin resistance (HOMA-I/R) was measured by the formula: HOMA-I/R=insulin (μU/ml)×glucose (mmol/l)/22.5 [17]. BMI was measured according to the method described by Novelli et al. [18].

Statistical analysis

The data are presented as mean±SD. Data from studies were analyzed using one-way analysis of variance. The relationship between plasma obestatin levels, BMI, lipid profile, or HOMA-IR was examined by Pearson's correlation coefficient. P-values less than 0.05 were considered statistically significant. All analyses were performed using SPSS for windows (version 10.0) (IBM Corporation, Armonk, New York, USA).


  Results Top


All the studied parameters are shown in [Table 1] and [Table 2] and [Figure 1].
Figure 1:

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Table 1: The studied biochemical parameters of the three groups

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Table 2: Correlation between obestatin levels and other studied parameters in both diabetic and obese rats

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Streptozotocin-induced diabetes in rats causes significant decrease in plasma obestatin, insulin, and BMI; however, it causes significant higher levels of glucose, HOMA-I/R, TG, and TC.

Obesity in rats causes lowering of plasma obestatin and insignificant change in glucose; however, obesity causes significantly higher levels of insulin, HOMA-I/R, TG, TC, and BMI when these values are compared with control rats.

On comparing obese animals with diabetic animals, obestatin was significantly lower in obese compared with diabetic animals; however, HOMA-I/R, TG, TC, and BMI were significantly higher in obese compared with diabetic animals.

In diabetic rats, plasma obestatin was negatively correlated with glucose, HOMA-I/R, TG, and TC, whereas it exhibited no significant correlation with BMI; however, it showed positive correlation with insulin [Table 2].

In obese rats, it was found that plasma obestatin levels were negatively correlated with all the studied parameters but exhibited no significant correlation with insulin [Table 2].


  Discussion Top


Obestatin is a peptide whose function is thought to be similar to that of ghrelin because of the common origin of both peptides. However, after the first report describing putative opposite effect of obestatin when compared with ghrelin [1], several studies disagreed with this proposal [14-18]. There are contradictory views with respect to concentrations of obestatin in obese patients. Some experiments revealed that in obese the peripheral blood exhibits significantly lower obestatin levels than in healthy normal weight individuals [19]; however, fasting obestatin levels were higher in infants with Prader-Willi syndrome, an obesity syndrome characterized by rapid weight gain and excessive food intake, compared with controls [20]. Guo et al. [21] have proved that plasma obestatin levels decreased in patients with chronic atrophic gastritis.

The present study revealed that plasma obestatin was significantly decreased in the diabetic group as compared with control, and there was a negative correlation between the plasma obestatin level and glucose. Similar result was documented by Qi et al. [22] and Lippl et al. [23], however, St-Pierre et al. [24] showed that normal and diabetic patients display similar levels of circulating obestatin in fasting condition. This negative relationship reflects the change of the glycemic parameter with obestatin and suggests an involvement of obestatin signaling in glucose homeostasis and diabetes. This point needs further research.

In the present study, we found that, compared with the control group, obese rats showed significantly decreased circulating levels of obestatin as well as significantly increased levels of all other metabolic parameters and increased BMI.

These findings are in accordance with a study by Zhang et al. [25] who suggested that obestatin levels were significantly reduced in obese rodents. In addition, studies in humans have shown that plasma obestatin levels were significantly lower in obese patients as compared with lean control, indicating a role for obestatin in long-term body weight regulation [26]. In addition, Zamrazilovα et al. [27] observed lower plasma obestatin levels in obese patients compared with women of normal weight and anorexic patients. Monteleone et al. [28] found that underweight anorexia nervosa patients displayed significantly increased circulating levels of obestatin when compared with normal control.

In the present study, obese rats showed negative correlation of obestatin with BMI, HOMA-I/R, and all metabolic parameters studied except insulin that showed no significant correlation with obestatin.

This suggests that basal secretion of obestatin may be influenced by adiposity and insulin resistance [2]. Anderwald-Stadler et al. [29] showed that humans who were markedly insulin resistant had lower fasting plasma obestatin concentration compared with those who were insulin sensitive, and concluded that obestatin secretion and/or clearance is altered with insulin resistance. Gutierre-Grobe et al. [30] found that lower levels of obestatin are associated with overweight, TG and TC levels, and insulin resistance conditions.

Guo et al. [21] reported lower level of preprandial obestatin in obese patients compared with normal weight individuals, which might be related to the disturbed satiety perception in obesity and anorexigenic effect of obestatin. However, the role of obestatin as anorexigenic hormone is not clearly understood [31]. Obestatin may exert its effect through central action opposing the foregut-induced orexigenic effect of ghrelin on food intake [32].

As obestatin inhibits jejunal contractile activity and suppresses gastric emptying activity, it cannot be excluded that its anorexigenic effect relies on the peripheral sites of action. Furthermore, inhibition of jejunal contraction could generate an afferent vagus signal to induce satiety in the central nervous system [33].


  Conclusion Top


The decrease in obestatin levels was associated with metabolic disorders and this may contribute, in part, to the pathophysiology of diabetes and obesity. Further experiments are needed to clarify the role of obestatin, to consider it as an endocrine marker that would reflect the changes in glucose and lipid metabolism, and to make obestatin a potential leading drug against obesity.


  Acknowledgements Top


Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.Qi X, Li L, Yang G, Liu J, Li K, Tang Y, et al. Circulating obestatin levels in normal subjects and in patients with impaired glucose regulation and type 2 diabetes mellitus. Clin Endocrinol (Oxf) 2007; 66:593-597.  Back to cited text no. 1
    
2.Lacquaniti A, Donato V, Chirico V, Buemi A, Buemi M. Obestatin: an interesting but controversial gut hormone. Ann Nutr Metab 2011; 59:193-199.  Back to cited text no. 2
    
3.Vicennati V, Genghini S, De Iasio R, Pasqui F, Pagotto U, Pasquali R. Circulating obestatin levels and the ghrelin/obestatin ratio in obese women. Eur J Endocrinol 2007; 157:295-301.  Back to cited text no. 3
    
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