• Users Online: 190
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
Year : 2016  |  Volume : 14  |  Issue : 3  |  Page : 101-108

Peptide tyrosine tyrosine (PYY) as a new strategy for treating obesity

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

Date of Submission04-Apr-2016
Date of Acceptance02-Aug-2016
Date of Web Publication15-Feb-2017

Correspondence Address:
Ahmed Mostafa Mahmoud
Lecturer of Medical Physiology, Faculty of Medicine, Sohag University, Sohag
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1687-1693.200146

Rights and Permissions

Obesity is a risk factor for obesity-related disorders such as type 2 diabetes mellitus, vascular disease, osteoarthritis, sleep apnea, and malignancy. Obesity cohinder the individual work capacity, and the cost for managing obesity complications is high.
The objective of this research was to study the role of pancreatic polypeptide family including neuropeptide Y and peptide tyrosine tyrosine (PYY) in obesity development and its metabolic changes.
Materials and methods
Twenty-seven adult female albino rats of a local strain were randomized into three equal groups for 5 weeks: sham-operated group, ovariectomized nontreated group, and ovariectomized treated group received PYY3–36 at a dose of 50 μg/kg, by intraperitoneal injection twice daily during the fifth week.
Peripheral PYY3–36 administration reduces food intake, body weight gain, and serum glucose in ovariectomized obese female rats.
PYY system may offer a new therapeutic strategy for obesity management and its metabolic abnormalities.

Keywords: metabolic disease, obesity, ovariectomized rats, pancreatic polypeptides, peptide tyrosine tyrosine

How to cite this article:
Mahmoud AM. Peptide tyrosine tyrosine (PYY) as a new strategy for treating obesity. Al-Azhar Assiut Med J 2016;14:101-8

How to cite this URL:
Mahmoud AM. Peptide tyrosine tyrosine (PYY) as a new strategy for treating obesity. Al-Azhar Assiut Med J [serial online] 2016 [cited 2021 Jun 14];14:101-8. Available from: http://www.azmj.eg.net/text.asp?2016/14/3/101/200146

  Introduction Top

Lifestyle modification strategies (diet and exercise) currently form the main treatments for obesity. However, results are generally disappointing, and the majority of people who attempt lifestyle modification regain any lost weight within 5 years [1]. Accumulation of excess body fat (and hence development of obesity) occurs when energy intake exceeds energy expenditure in the long term [2]. Our progressive understanding of the physiological mechanisms of appetite regulation should help with the development of future pharmacological approaches to combat obesity [3].

Pancreatic polypeptide family includes neuropeptide tyrosine (NPY), peptide tyrosine tyrosine (PYY), and pancreatic polypeptide. Its name derives from the single-letter code (Y) for the amino acid tyrosine, as it contains several tyrosine residues. These peptides are structurally and biologically similar, but they are synthesized and secreted from different sources [4].

PYY is released from the L cells of the gastrointestinal tract, with increasing tissue concentrations found in the distal portions [5]. In the circulation, it exists in two major forms: PYY1–36 and PYY3–36. PYY1–36 is rapidly proteolyzed by enzyme dipeptidyl-peptidase IV. The cleaved product, PYY3–36, is bioactive. PYY is able to cross the blood–brain barrier (BBB) by transmembrane diffusion from the circulation [5].

PYY is also considered an appetite-regulating hormone given that its secretion reduces hunger and imparts satiety [6].

Obesity-related disorders such as type 2 diabetes, vascular diseases, osteoarthritis, hazards of bariatric surgery, and the economic burden in treating obesity complications led us to find another strategy for treating obesity. Therefore, we aimed to investigate the effect of intraperitoneal injection of a potent Y2 receptor agonist PYY3–36 on ovariectomy (OVX)-induced obesity and its metabolic abnormalities.

  Materials and methods Top

This study was carried out in the Medical Physiology Department, Faculty of Medicine, Sohag University. This was approved by Research Ethics Committee considering care and use of laboratory animals in Sohag University.

Animals and groups

Twenty-seven adult albino rats of local strain, of body weight ranging between 150 and 200 g at the beginning of this study, were used. The age of these rats was about 8–10 weeks at the start of the experimental work. They were housed in groups in cages (20 cm width×32 cm length×20 cm height) at room temperature with natural light/dark cycles for 1 week to acclimatize them to lab conditions. Rats were fed a standard diet of commercial rat chow (El-Gomhoria Company, Cairo, Egypt) and tap water ad libitum until the time of the experiment [6]. During the acclimatization period, daily food intake was measured to know the mean daily food intake per rat. The rats were divided into three equal groups: (a) control sham-operated group, (b) ovariectomized nontreated group, and (c) ovariectomized treated group. The animals were accustomed to the injection procedure by intraperitoneal injection with saline (0.5 ml/rat) for 2 days before PYY3–36 administration [7]. Next, each rat received PYY3–36 (Sigma Aldrich, 2033 Westport Center Dr., St. Louis, MO 63146, USA) at a dose level of 50 μg/kg, by intraperitoneal injection twice daily during the fifth week. It was prepared by dissolving PYY3–36 in saline solution [8].

Ovariectomy [9]

Lee index was used to determine obesity in rats using body weight and nasoanal length. It was measured at the beginning of the study, at the end of the fourth week, and at the end of the fifth week. Lee index was calculated for each rat according to the following formula: Cube root of body weight (g)×10/nasoanal length (mm) [10]. Obesity was considered when the Lee index was greater than 0.3. At the end of the fifth week, rats were killed after an overnight fast by decapitation, and blood samples were collected, allowed to clot at room temperature, and then centrifuged at 3000 rpm for 15 min in a cooling centrifuge (Hettich centrifuge; Andreas Hettich GmbH & Co. KG, Föhrenstr 12, D-78532 Tuttlingen, Germany). Serum was then withdrawn into identified Eppendorf tubes and stored at −20°C until the determination of hypothalamic NPY concentration [11], total serum cholesterol [12], LDL cholesterol (LDL-C) [13], HDL cholesterol (HDL-C) [14], serum glucose [15], and serum leptin [16].

Statistical analysis

Statistical analysis was performed using the computer software program prism (Comshare’s version of a decision support system), version 3.3. Data were expressed as mean±SE. Analysis of variance with Bonferroni’s multiple comparison test was used to find intergroup significance. P value less than 0.05 was considered statistically significant.

  Results Top

OVX caused a significantly higher body weight from the second week until the end of the study, as compared with the sham-operated control group. Injection of PYY3–36 caused a significantly lower body weight as compared with the OVX group, as shown in [Table 1].
Table 1 Body weight changes in the different groups

Click here to view

Lee index changes in the different groups

In OVX groups, rats also had a Lee index higher than 0.3 at the end of the fourth and fifth weeks and were considered obese. The Lee index was significantly higher in the OVX group as compared with the control group. Injection of PYY3–36 during the fifth week did not decrease the Lee index below 0.3 and rats were still obese, but the Lee index in the OVXT group was significantly lower as compared with the OVX group and insignificant as compared with the sham-operated control group, as shown in [Table 2].
Table 2 The Lee index in the different groups

Click here to view

Time-course changes in daily food intake in the different studied groups

In ovariectomized groups, food intake was significantly lower during the first week and then significantly higher until the end of the study as compared with the control group. Injection of PYY3–36 caused a significantly lower food intake as compared with the sham-operated control and OVX groups ([Table 3]).
Table 3 Daily food intake changes in the different groups

Click here to view

The changes in weight of the gastrocolic omentum fat in the different studied groups

In the OVX group, the weight of the gastrocolic omentum fat (GCOF) was significantly higher as compared with the control group. Injection of PYY3–36 caused a significantly lower weight of the GCOF as compared with the OVX group, as shown in [Table 4]; however, it was still significantly higher than the sham-operated control group.
Table 4 The weight of GCOF in different groups

Click here to view

Serum glucose, leptin, and hypothalamic neuropeptide Y concentrations in the different studied groups

Serum glucose level was significantly higher in the ovariectomized groups as compared with the corresponding control groups. On the other hand, injection of PYY3–36 caused a significantly lower serum glucose level in OVX as compared with nontreated groups; however, the levels were still significantly higher than the control groups ([Table 5]).
Table 5 Serum glucose, serum leptin, and hypothalamic NPY in the different groups

Click here to view

Serum leptin was significantly higher in the ovariectomized groups as compared with the corresponding control groups. Injection of PYY3–36 caused a significantly lower serum leptin level in OVX groups as compared with noninjected groups, but the levels remained significantly higher than the control groups ([Table 6]).
Table 6 Serum level of lipid profile in ovariectomized groups

Click here to view

It was observed that the hypothalamic NPY was significantly lower in high-fat diet groups as compared with control groups. On the other hand, NPY was significantly higher in the OVX group as compared with the sham-operated control group. Injection of PYY3–36 caused a significantly lower hypothalamic NPY level in both OVX and high-fat diet groups as compared with both control and nontreated groups.

Serum level of total cholesterol, triglycerides, HDL-cholesterol, and LDL-cholesterol in different studied groups

In ovariectomized groups, in comparison with the sham-operated control group, the serum levels of total cholesterol and LDL-C were significantly higher associated with a significant lower serum levels of triglycerides (TGs) and HDL-C. Injection of PYY3–36 to ovariectomized rats caused insignificant differences on serum lipid profile as compared with the OVX group.

  Discussion Top

Results of the previous studies that have examined the effect of PYY3–36 administration on food intake and body weight regulation were contradictory. Peripheral administration of PYY3–36 reduced food intake and decreased body weight gain in both humans and rodents. The anorectic effect of peripheral PYY3–36 may be mediated via the presynaptic inhibitory Y2 receptor present on arcuate NPY neurons [5]. Intravenous PYY infusion has been found to decrease energy intake and reduce hunger in healthy individuals [7] and those with obesity [17]. It has been reported that fasting and postprandial PYY levels are lower in those with obesity and higher in normal-weight individuals [18]. Another study observed that acute and chronic administration of PYY3–36 in rats either increased or did not change food intake and body weight [19].

In the present study, induction of obesity was performed by OVX. The occurrence of obesity was confirmed by the Lee index, and a Lee index of 0.3 or more indicated obesity [20]. In experimental rats of this study, it was higher than 0.3. After induction of obesity, rats were treated by intraperitoneal administration of PYY3–36 during the fifth week with continuous standard rat chow diet in OVX groups.

OVX caused a significantly higher body weight from the second week until the end of the study as compared with the control group. The correlated increase in body weight and food intake found in the present study following OVX is in agreement with Abdel-Hakim et al. [21], Zhang et al. [22], and Pósa et al. [23] who explained the increase in body weight by the increase in food intake. Another possible mechanism of increased body weight is the increased lipogenesis and decreased lipolysis, which was evidenced in the present work by a significant increase in Lee index and weight of GCOF. This is in agreement with Abdel Razek et al. [24].

The present results revealed that OVX was accompanied with significantly lower food intake during the first week and then increased significantly until the end of the study as compared with the control group. There were several possibilities that explained the mechanism of lowered food intake following OVX. Stressors such as surgical trauma, anesthesia, and manipulation of internal viscera may result in this reduction [25]. Stengel et al. [26] found that surgical stress resulted in activation of the brain corticotropin-releasing factor (CRF) receptors. In the brain, CRF is well established to activate sympathetic outflow while reducing gastric vagal activity. A certain study supported the role of this brain stress pathway by the blockade of delayed gastric emptying immediately after surgery in mice lacking the CRF1 receptor [27].

The mechanism of increased food intake after OVX may be because of the increased hypothalamic NPY concentration, as found in the present study and by Jiang et al. [28] and Zhang et al. [29] The increased hypothalamic NPY concentration may be because of the lack of estrogen hormone, as found by Rivera et al. [30] and Santollo et al. [31]. Estrogen has been proposed to act directly and indirectly to decrease NPY release and to decrease food intake. Previous study showed colocalization of estradiol and NPY immunoreactivity in some neurons in the ARC nucleus, which suggests a direct genomic modulation of NPY neurosecretion by estrogens in the hypothalamus [32]. Another study detected that estrogen decreased the expression of NPY in the ARC nucleus [33] and decreased NPY release in the paraventricular nucleus through estrogen receptors, which were expressed by NPY neurons in the hypothalamus [34].

In OVX rats, the weight of GCOF was significantly higher as compared with the control group [21],[35]. There are several mechanisms underlying the visceral fat accumulation in OVX rats. OVX-induced hyperphagia resulted in excess accumulation of fat, as found by Abdel-Hakim et al. [21] It may also be because of cessation of endogenous estrogen production [36]. Estrogen has direct effects on abdominal adipocytes to stimulate lipolysis through higher lipoprotein lipase activity, and the opposite occurs in subcutaneous fat. Thus, loss of subcutaneous fat and accumulation of visceral fat occur after OVX [24],[37].

In the present study, it was found that OVX produced a significantly higher serum level of total cholesterol and LDL-C and a significantly lower serum level of TGs and HDL-C. Similar results were reported by Elbassuoni et al. [38] and El Habachi et al. [36]. These disturbances in lipid profile could be attributed to the greater visceral fat accumulation, and this was evident in the present study by greater GCOF weight. The reduction of HDL-C and TGs after OVX might be related to estrogen withdrawal. Estrogen decreases HDL catabolism through reduction of hepatic lipase activity [39] and increases TG biosynthesis through activation of glucose-6-phosphate dehydrogenase, which is an indicator of the glucose flux through the pentose phosphate pathway producing nicotinamide adenine dinucleotide phosphate hydrogen [40].

Peripheral administration of PYY3–36 after induction of obesity in OVX rats significantly lowered food intake, body weight, Lee index, GCOF weight, hypothalamic NPY, serum leptin, and glucose, as compared with control groups. It is possible that the body weight and Lee index reduction with peripheral administration of PYY is primarily driven by reductions in food intake and weight of GCOF. This is in agreement with Reidelberger et al. [41] and Mittapalli and Roberts [42].

The reduction of food intake with PYY3–36 administration in the ovariectomized group is in agreement with the study by Papadimitriou et al. [43] Within the central nervous system, PYY exerts its anorectic effects via actions in the ARC nucleus of the hypothalamus. The ARC is in close proximity to the deficient BBB of the median eminence of the hypothalamus, thus allowing this region to respond rapidly to the released gut hormones in the circulation, including PYY, which is able to cross the BBB by transmembrane diffusion from the circulation [44],[45]. Evidence confirmed that PYY3-36 exerted the inhibition on food intake in a Y2-dependent manner, as Y2 receptors are abundantly expressed on NPY neurons in the ARC of the hypothalamus. Another study reported that the anorexigenic actions of PYY were abolished in Y2 knockout mice and blocked by Y2 antagonist [42]. Y2 receptors primarily act as presynaptic autoreceptors modulating endogenous NPY release. In particular, PYY inhibits NPY neurons and reduces hypothalamic NPY mRNA and/or protein content as found in the present results and by Yulyaningsih et al. [46].

A certain study observed that acute and chronic administration of PYY3–36 in rats could not produce any effect on food intake and body weight [47], whereas another study reported that peripheral administration of PYY3–36 increased food intake and body weight [19]. Challis et al. [48] observed the short-term anorectic effects, but none after 7 days of administration on either cumulative weight gain or food intake. Several possibilities may cause inconsistency in the effect of PYY3–36 administration on food intake. One possibility may be caused by different experimental protocols or animal strains studied [49]. Another possibility is that insufficient acclimatization to handling and injection of animals results in a stress-induced reduction in appetite and a subsequent failure of PYY3–36 to further reduce food intake [50]. The broad distribution of the Y receptor subtypes both centrally and peripherally with the antagonistic effects of stimulation of the different subtypes and the fact that PYY could act both centrally and peripherally when peripherally administered may explain this discrepancy.

Several possibilities explain the reduction of visceral fat with PYY3–36 administration. Adams et al. [51] and Chelikani et al. [52] found that this effect may be secondary to reduced food intake, and/or reflect a direct action of PYY3–36 on fat-mobilizing or fat-utilizing tissues, as diminished food intake in response to PYY3–36 treatment may lower the insulin: glucagon ratio, increase lipolysis, and decrease de novo lipogenesis.

The reduction in the body weight and GCOF weight may be the cause of significantly lower serum level of leptin with PYY33–36 administration as compared with control groups [53],[54]. However, another research documented that PYY3–36 produced an insignificant effect on serum leptin [55].

Insulin resistance (IR) can be defined as a state of reduced responsiveness to normal circulating levels of insulin; it plays a major role in the development of type 2 diabetes [56]. There are multiple mechanisms involved in the development of IR, including the following: excess lipid accumulation and dietary fatty acid might be involved in altering the cell membrane composition, thereby impeding the binding of insulin to its receptor [57], inflammatory response, and altered cytokine production from expanded adipose tissue and subsequent paracrine/autocrine-mediated cellular IR [58], mitochondrial dysfunction, and consequently dysfunction of mitochondrial fatty acid oxidative capacity [59]. Previous results suggested that hypothalamic NPY neurons modulate the inhibitory effect of insulin on glucose production via efferent sympathetic nerves innervating the liver and caused IR [60],[61]. Therefore, the hypoglycemic effect of peripherally administered PYY3–36 as found in the present study and by Chandarana et al. [62] may be secondary to reduction of food intake, Lee index, body weight, GCOF weight, and NPY release. All these factors may improve insulin sensitivity and glucose disposal [63].

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Weiss EC, Galuska DA, Kettel Khan L, Gillespie C, Serdula MK. Weight regain in U.S. adults who experienced substantial weight loss, 1999–2002. Am J Prev Med: 2007; 33:34–40.  Back to cited text no. 1
Hill JO, Wyatt HR, Peters JC. Energy balance and obesity. Circulation 2012; 126:126–132.  Back to cited text no. 2
Sellayah D, Sikder D. Feeding the heat on brown fat. Ann N Y Acad Sci 2013; 1302:11–23.  Back to cited text no. 3
Germain N, Minnion JS, Tan T, Shillito J, Gibbard C, Ghatei M, Bloom S. Analogs of pancreatic polypeptide and peptide YY with a locked PP-fold structure are biologically active. Peptides 2013; 39:6–10.  Back to cited text no. 4
Sobrino Crespo C, Perianes Cachero A, Puebla Jiménez L, Barrios V, Arilla Ferreiro E. Peptides and food intake. Front Endocrinol (Lausanne) 2014; 5:58.  Back to cited text no. 5
Ahmadi R, Oryan Sh. Effects of ovariectomy or orchidectomy and estradiol valerate or testosterone enanthate replacement on serum insulin in rats. Pak J Biol Sci 2008; 11:306–308.  Back to cited text no. 6
Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL et al. Gut hormone PYY(3-36) physiologically inhibits food intake. Nature 2002; 418:650–654.  Back to cited text no. 7
Wang L, Gourcerol G, Yuan PQ, Wu SV, Million M, Larauche M, Taché Y. Peripheral peptide YY inhibits propulsive colonic motor function through Y2 receptor in conscious mice. Am J Physiol Gastrointest Liver Physiol 2010; 298:G45–G56.  Back to cited text no. 8
Zhang Y, Lai WP, Leung PC, Wu CF, Wong MS. Short- to mid-term effects of ovariectomy on bone turnover, bone mass and bone strength in rats. Biol Pharm Bull 2007; 30:898–903.  Back to cited text no. 9
Novelli EL, Diniz YS, Galhardi CM, Ebaid GM, Rodrigues HG, Mani F et al. Anthropometrical parameters and markers of obesity in rats. Lab Anim 2007; 41:111–119.  Back to cited text no. 10
Kuo LE, Kitlinska JB, Tilan JU, Li L, Baker SB, Johnson MD et al. Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome. Nat Med 2007; 13:803–811.  Back to cited text no. 11
Allain C, Poon L, Chon C, Richmond U, Fu P. Enzymatic determination of total serum cholesterol. Clin Chem 1974; 20:470–475.  Back to cited text no. 12
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18:499–502.  Back to cited text no. 13
Lopes-Virella M, Stone P, Ellis S, Coldwell J. Cholesterol determinations in high density liproproteins separated by three methods. Clin Chem 1977; 23:882–884.  Back to cited text no. 14
Genuth S, Alberti K, Bennett P, Buse J, Defronzo R, Kahn R. Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 2003; 26:3160–3167.  Back to cited text no. 15
Cirmanová V, Bayer M, Stárka L, Zajícková K. The effect of leptin on bone − an evolving concept of action. Physiol Res 2008; 57:43–51.  Back to cited text no. 16
Batterham RL, Cohen MA, Ellis SM, Le Roux CW, Withers DJ, Frost GS et al. Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med 2003; 349:941–948.  Back to cited text no. 17
Le Roux CW, Batterham RL, Aylwin SJ, Patterson M, Borg CM, Wynne KJ et al. Attenuated peptide YY release in obese subjects is associated with reduced satiety. Endocrinology 2006; 147:3–8.  Back to cited text no. 18
Tschöp M, Castañeda TR, Joost HG, Thöne-Reineke C, Ortmann S, Klaus S et al. Physiology: does gut hormone PYY3-36 decrease food intake in rodents? Nature 2004; 430:165.  Back to cited text no. 19
Long M, Zhou J, Li D, Zheng L, Xu Z, Zhou S. Long-term over-expression of neuropeptide Y in hypothalamic paraventricular nucleus contributes to adipose tissue insulin resistance partly via the Y5 receptor. PLoS One 2015; 10:e0126714  Back to cited text no. 20
Abdel-Hakim SM, Ibrahim MY, Ibrahim HM, Ibrahim MM. The effect of ghrelin antagonist (D-Lys3) GHRP-6 on ovariectomy-induced obesity in adult female albino rats. Endocr Regul 2014; 48:126–134.  Back to cited text no. 21
Zhang R, Su D, Zhu W, Huang Q, Liu M, Xue Y et al. Estrogen suppresses adipogenesis by inhibiting S100A16 expression. J Mol Endocrinol 2014; 52:235–244.  Back to cited text no. 22
Pósa A, Szabó R, Kupai K, Csonka A, Szalai Z, Veszelka M et al. Exercise training and calorie restriction influence the metabolic parameters in ovariectomized female rats. Oxid Med Cell Longev 2015; 2015:787063.  Back to cited text no. 23
Abdel Razek AMH, Tag MH, Tantawy MH, Thabet H. Soy isoflavones reduce adiposity via increasing estrogen receptor beta expression in ovariectomized female rats. Egypt Acad J Biolog Sci 2013; 5:59–71.  Back to cited text no. 24
Maniscalco JW, Kreisler AD, Rinaman L. Satiation and stress-induced hypophagia: examining the role of hindbrain neurons expressing prolactin-releasing peptide or glucagon-like peptide. Front Neurosci 2013; 6:199.  Back to cited text no. 25
Stengel A, Goebel-Stengel M, Wang L, Luckey A, Hu E, Rivier J, Taché Y. Central administration of pan-somatostatin agonist ODT8-SST prevents abdominal surgery-induced inhibition of circulating ghrelin, food intake and gastric emptying in rats. Neurogastroenterol Motil 2011; 23:e294–e308.  Back to cited text no. 26
Sakamoto R, Matsubara E, Nomura M, Wang L, Kawahara Y, Yanase T et al. Roles for corticotropin-releasing factor receptor type 1 in energy homeostasis in mice. Metabolism 2013; 62:1739–1748.  Back to cited text no. 27
Jiang JM, Sacco SM, Ward WE, Jiang JM, Sacco SM, Ward WE et al. Ovariectomy-induced hyperphagia does not modulate bone mineral density or bone strength in rats. J Nutr 2008; 138:2106–2110.  Back to cited text no. 28
Zhang Y, Na X, Zhang Y, Li L, Zhao X, Cui H. Isoflavone reduces body weight by decreasing food intake in ovariectomized rats. Ann Nutr Metab 2009; 54:163–170.  Back to cited text no. 29
Rivera HM, Santollo J, Nikonova LV, Eckel LA. Estradiol increases the anorexia associated with increased 5-HT(2C) receptor activation in ovariectomized rats. Physiol Behav 2012; 105:188–194.  Back to cited text no. 30
Santollo J, Marshall A, Daniels D. Activation of membrane-associated estrogen receptors decreases food and water intake in ovariectomized rats. Endocrinology 2013; 154:320–329.  Back to cited text no. 31
Brown DX, Evans M. Choosing between GLP-1 receptor agonists and DPP-4 inhibitors: a pharmacological perspective. J Nutr Metab 2012; 2012:381713.  Back to cited text no. 32
Litwak SA, Wilson JL, Chen W, Garcia-Rudaz C, Khaksari M, Cowley MA, Enriori PJ. Estradiol prevents fat accumulation and overcomes leptin resistance in female high-fat diet mice. Endocrinology 2014; 155:4447–4460.  Back to cited text no. 33
Dhillon SS, Belsham DD. Estrogen inhibits NPY secretion through membrane-associated estrogen receptor (ER)-α in clonal, immortalized hypothalamic neurons. Int J Obes (Lond) 2011; 35:198–207.  Back to cited text no. 34
Ke JY, Kliewer KL, Hamad EM, Cole RM, Powell KA, Andridge RR et al. The flavonoid, naringenin, decreases adipose tissue mass and attenuates ovariectomy-associated metabolic disturbances in mice. Nutr Metab (Lond) 2015; 12:1.  Back to cited text no. 35
El Habachi NM, Maklad HM, Sharara GM, Allam EA, Fawzy EM. A comparative study between the effect of 17-β estradiol and antioxidants combination on some menopausal changes in oophorectomised rats. Middle East Fertility Society J 2014; 19:303–313.  Back to cited text no. 36
Lizcano F, Guzmán G. Estrogen deficiency and the origin of obesity during menopause. Biomed Res Int 2014; 2014:757461.  Back to cited text no. 37
Elbassuoni E, Ragy M, Aziz N. Protective effect of GHRP-6 and estrogen supplementation against some cardiometabolic risk factors in ovariectomized rats. Endocr Regul 2012; 46:73–81.  Back to cited text no. 38
Kumar P, Bhandari U, Jamadagni S. Fenugreek seed extract inhibit fat accumulation and ameliorates dyslipidemia in high fat diet-induced obese rats. Biomed Res Int 2014; 2014:606021.  Back to cited text no. 39
Abdel-Hakim SM, Ibrahim HM, Elbassuoni EA, Ragy MM. Effect of ovariectomy with and without hormonal replacement therapy on some cardiovascular risk factors in female albino rats. El-Minia Med J 2010; 21:14–32.  Back to cited text no. 40
Reidelberger RD, Haver AC, Chelikani PK, Buescher JL. Effects of different intermittent peptide YY (3-36) dosing strategies on food intake, body weight, and adiposity in diet-induced obese rats. Am J Physiol Regul Integr Comp Physiol 2008; 295:R449–R458.  Back to cited text no. 41
Mittapalli KG, Roberts E. Ligands of the neuropeptide Y Y2 receptor. BMCL Digest 2014; 24:430–441.  Back to cited text no. 42
Papadimitriou MA, Krzemien AA, Hahn PM, van Vugt DA. Peptide YY(3-36)-induced inhibition of food intake in female monkeys. Brain Res 2007; 1175:60–65.  Back to cited text no. 43
Smitka K, Papezova H, Vondra K, Hill M, Hainer V, Nedvidkova J. The role of ‘mixed’ orexigenic and anorexigenic signals and autoantibodies reacting with appetite-regulating neuropeptides and peptides of the adipose tissue-gut-brain axis: relevance to food intake and nutritional status in patients with anorexia nervosa and bulimia nervosa. Int J Endocrinol 2013; 2013:483145.  Back to cited text no. 44
Boguszewski CL, van der Lely AJ. The role of the gastrointestinal tract in the control of energy balance. Trans Gastrointest Canc 2015; 4:3–13.  Back to cited text no. 45
Yulyaningsih E, Zhang L, Herzog H, Sainsbury A. NPY receptors as potential targets for anti-obesity drug development. Br J Pharmacol 2011; 163:1170–1202.  Back to cited text no. 46
Boggiano MM, Chandler PC, Oswald KD, Rodgers RJ, Blundell JE, Ishii Y et al. PYY3-36 as an anti-obesity drug target. Obes Rev 2005; 6:307–322.  Back to cited text no. 47
Challis BG, Coll AP, Yeo GS, Pinnock SB, Dickson SL, Thresher RR et al. Mice lacking pro-opiomelanocortin are sensitive to high-fat feeding but respond normally to the acute anorectic effects of peptide-YY(3-36). Proc Natl Acad Sci USA 2004; 101:4695–4700.  Back to cited text no. 48
Abbott CR, Small CJ, Sajedi A, Smith KL, Parkinson JR, Broadhead LL et al. The importance of acclimatisation and habituation to experimental conditions when investigating the anorectic effects of gastrointestinal hormones in the rat. Int J Obes (Lond) 2006; 30:288–292.  Back to cited text no. 49
Parkinson JR, Dhillo WS, Small CJ, Chaudhri OB, Bewick GA, Pritchard I et al. PYY3-36 injection in mice produces an acute anorexigenic effect followed by a delayed orexigenic effect not observed with other anorexigenic gut hormones. Am J Physiol Endocrinol Metab 2008; 294:E698–E708.  Back to cited text no. 50
Adams SH, Lei C, Jodka CM, Nikoulina SE, Hoyt JA, Gedulin B et al. PYY[3-36] administration decreases the respiratory quotient and reduces adiposity in diet-induced obese mice. J Nutr 2006; 136:195–201.  Back to cited text no. 51
Chelikani PK, Haver AC, Reidelberger RD. Intermittent intraperitoneal infusion of peptide YY(3-36) reduces daily food intake and adiposity in obese rats. Am J Physiol Regul Integr Comp Physiol 2007; 293:R39–R46.  Back to cited text no. 52
Unniappan S, Kieffer TJ. Leptin extends the anorectic effects of chronic PYY(3-36) administration in ad libitum-fed rats. Am J Physiol Regul Integr Comp Physiol 2008; 295:R51–R58.  Back to cited text no. 53
Hsieh CJ, Wang PW, Chen TY. The relationship between regional abdominal fat distribution and both insulin resistance and subclinical chronic inflammation in non-diabetic adults. Diabetol Metab Syndr 2014; 6:49.  Back to cited text no. 54
Oliveira KJ, Paula GS, Costa-e-Sousa RH, Souza LL, Moraes DC, Curty FH, Pazos-Moura CC. Peptide YY (PYY)3-36 modulates thyrotropin secretion in rats. J Endocrinol 2006; 191:459–463.  Back to cited text no. 55
Ford AH, Flicker L, Hankey GJ, Yeap BB, Chubb SA, Golledge J, Almeida OP. Insulin resistance and depressive symptoms in older men: the health in men study. Am J Geriatr Psychiatry 2015; 23:872–880.  Back to cited text no. 56
Nourmohammdi M, Ejtahed H, Mirmiran P, Hekmatdoost A. Dietary fatty acid composition and metabolic syndrome: a review. Nutr Sci Diet J 2015; 1:28–36.  Back to cited text no. 57
Carolan E, Tobin LM, Mangan BA, Corrigan M, Gaoatswe G, Byrne G et al. Altered distribution and increased IL-17 production by mucosal-associated invariant T cells in adult and childhood obesity. J Immunol 2015; 194:5775–5780.  Back to cited text no. 58
Montgomery MK, Turner N. Mitochondrial dysfunction and insulin resistance: an update. Endocr Connect 2015; 4:R1–R15.  Back to cited text no. 59
Van den Hoek AM, van Heijningen C, Schröder-van der Elst JP, Ouwens DM, Havekes LM, Romijn JA et al. Intracerebroventricular administration of neuropeptide Y induces hepatic insulin resistance via sympathetic innervation. Diabetes 2008; 57:2304–2310.  Back to cited text no. 60
Lam CK, Chari M, Lam TK. CNS regulation of glucose homeostasis. Physiology 2009; 24:159–170.  Back to cited text no. 61
Chandarana K, Gelegen C, Irvine EE, Choudhury AI, Amouyal C, Andreelli F et al. Peripheral activation of the Y2-receptor promotes secretion of GLP-1 and improves glucose tolerance. Mol Metab 2013; 2:142–152.  Back to cited text no. 62
Sala PC, Torrinhas RS, Giannella-Neto D, Waitzberg DL. Relationship between gut hormones and glucose homeostasis after bariatric surgery. Diabetol Metab Syndr 2014; 6:87  Back to cited text no. 63


  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]

This article has been cited by
1 The effect of peptide tyrosine tyrosine (PYY336), a selective Y2 receptor agonist on streptozotocin-induced diabetes in albino rats
Heba A. Abdel-Hamid,Mona M. I. Abdalla,Nagwa M. Zenhom,Rasha F. Ahmed
Endocrine Regulations. 2019; 53(1): 26
[Pubmed] | [DOI]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
   Materials and me...
   Article Tables

 Article Access Statistics
    PDF Downloaded568    
    Comments [Add]    
    Cited by others 1    

Recommend this journal