|Year : 2014 | Volume
| Issue : 4 | Page : 230-237
Evaluation of effects of diet on serum obestatin levels in over-weight patients with polycystic ovary syndrome
Gülsüm Yildiz1, Aykan Yücel1, Volkan Noyan1, Mehmet Suhha Bostanci2, Nevin Sa söz1
1 Department of Obstetrics and Gynecology, Faculty of Medicine, Kirikkale University, Kirikkale, Turkey
2 Department of Obstetrics and Gynecology, Faculty of Medicine, Sakarya University, Sakarya, Turkey
|Date of Submission||15-Sep-2014|
|Date of Decision||21-Nov-2014|
|Date of Acceptance||11-Nov-2014|
|Date of Web Publication||11-Dec-2014|
Mehmet Suhha Bostanci
Department of Obstetrics and Gynecology, Faculty of Medicine, Sakarya University, Sakarya
Source of Support: None, Conflict of Interest: None
Objective: The aim was to evaluate effects of diet on serum obestatin levels in overweight or obese patients with polycystic ovary syndrome. Materials and Methods: This was prospective case-control study (preliminary study). Twenty-two overweight and obese women diagnosed with polycystic ovary syndrome (PCOS) and 22 body mass index (BMI) and age-matched non-PCOS controls. Serum obestatin levels were measured using enzyme-linked immunosorbent assay. Effects of weight loss on obestatin level and relationships between obestatin levels and hormonal and biochemical parameters were evaluated in PCOS. Results: In PCOS group, there was no significant difference in the obestatin levels between before and after the diet. In controls, there was no significant difference in the weight loss or the obestatin levels at baseline and after the diet. In both groups, there was no correlation between obestatin levels and homeostasis model assessment-insulin resistance or BMI before or after the diet. In PCOS group, obestatin levels were negatively correlated with high-density lipoprotein before the diet and obestatin levels were negatively correlated with waist-hip ratio after the diet. Conclusions: To the best of our knowledge, this is the first study to investigate the effects of weight loss on obestatin levels in over-weight and obese women with PCOS. We found no difference in the obestatin levels before and after the diet in PCOS and control groups. Our findings suggest that different mechanisms play critical roles in the regulation of obestatin levels when BMI is relatively higher. There is a need for large-scale and long-term follow-up, prospective studies to evaluate the effects of obestatin in PCOS.
Keywords: Diabetes, obesity, obestatin, polycystic ovary syndrome
|How to cite this article:|
Yildiz G, Yücel A, Noyan V, Bostanci MS, Sa söz N. Evaluation of effects of diet on serum obestatin levels in over-weight patients with polycystic ovary syndrome
. J Obes Metab Res 2014;1:230-7
|How to cite this URL:|
Yildiz G, Yücel A, Noyan V, Bostanci MS, Sa söz N. Evaluation of effects of diet on serum obestatin levels in over-weight patients with polycystic ovary syndrome
. J Obes Metab Res [serial online] 2014 [cited 2021 May 15];1:230-7. Available from: https://www.jomrjournal.org/text.asp?2014/1/4/230/146802
| Introduction|| |
Polycystic ovary syndrome (PCOS) is a complex, chronic metabolic disease that affects about 5-10% of women in the reproductive age, characterized by chronic oligo-anovulation and hyperandrogenism.  In PCOS, enhancement of adipose tissue formation related to obesity leads to more and more complex disease course and individual's tendency to gain weight also increases as presentation of the disease gets more complicated.  40-60% of women with PCOS are overweight or obese.  It has been determined that typical symptoms and signs of PCOS such as obesity, high blood glucose level, insulin resistance and hormonal imbalance could be improved by nutritional management. 
Obestatin was discovered by Zhang et al. in 2005, which is an anorectic peptide consisting of 23 amino acids and it is encoded by the same gene as ghrelin.  The distribution of obestatin in human tissues is poorly understood. It has been showed by immunofluorosecence technique using specific antiserum against obestatin that there were obestatin immunoreactivity in small and large intestine, pancreas, hypothalamus and pituitary gland; , in cells of gastric mucosa and myenteric plexus, and in Leydig cells of testis in rats.  It has been suggested that obestatin suppresses appetite, reduces food intake, and it behaves as a physiological opponent to ghrelin. , However, the finding that obestatin opposes ghrelin's stimulatory effect has been questioned by later studies and some of the authors stated that obestatin and ghrelin have similar effects on appetite and food intake. ,, In human studies, higher levels of plasma obestatin in obese subjects compared with lean subjects suggests that the obestatin may play a role in the long-term regulation of body weight. ,, In a study, it has been found that obestatin is closely related with metabolic parameters, obesity and insulin resistance; and obestatin level increases after weight loss.  To our knowledge, there is no study in the literature that investigates serum obestatin levels in over-weight and obese women with PCOS and the effects of weight loss on serum obestatin levels in over-weight and obese women with PCOS. Given that high prevalence of obesity in PCOS , and possible effects of obestatin on energy metabolism, obesity and gonadal functions,  it can be suggested that obestatin may also be a marker of metabolic and reproductive phenomena in PCOS.
The aim of this study was to evaluate serum obestatin levels and relationship between obestatin levels with weight loss, hormonal and biochemical parameters in obese and overweight women with PCOS.
| Materials and methods|| |
Twenty-nine women with PCOS and twenty seven non-PCOS controls were enrolled in the study, who were admitted to Obstetrics and Gynecology Department, Faculty of Medicine, Kirikkale University. Informed consent and approval of the study protocol were provided by the Kirikkale University ethics committee. Study participants were obese or overweight (body mass index [BMI] ≥>25 kg/m 2 ) and aged between 18 and 35 years. According to recommendations of "Rotterdam European Society for Human Reproduction/American Society of Reproductive Medicine-sponsored PCOS Consensus Workshop Group," which were revised and introduced in 2003;  the presence of two of three of the following criteria were used to make a diagnosis of PCOS: Oligomenorrhea/amenorrhea, clinical and/or biochemical hyperandrogenism and polycystic ovaries. BMI and age-matched, non-PCOS controls with regular menstruation had served as controls. Women were not eligible if they had ultrasound findings compatible with ovarian cysts, endometrioma, myoma or polyp or had taken any medication in the past 3 months diabetes mellitus or had hypertension, acute or chronic liver disease, renal impairment, endocrine disorders such as thyroid dysfunction, adrenal hyperplasia, hyperprolactinemia, cushing syndrome and history of gastric or intestinal surgery. Seven women in PCOS group and five women in non-PCOS controls were noncompliant to the diet. Those individuals were excluded and in the study 22 with PCOS and 22 non-PCOS controls were evaluated.
Anthropometric parameters including height, weight, waist, and hip circumferences were measured in all individuals. BMI was calculated using the following formula: BMI = Body weight(kg)/height 2 (m 2 ).  Body fat percentage (BFP) was calculated by the formula described by Deurenberg et al.:  BFP = (1.2 × BMI)+(0.23 × age)−[10.8× × gender]−5.4 where, male gender = 1 and female gender = 0. The severity of hirsutism was measured using the modified Ferriman-Gallwey (mFG) map scoring system. The amount of terminal hairs (i.e. those >0.5 cm) scored from 0 (no terminal hair) to 4 (frankly virile) for the nine body areas including upper lip, chin, chest, upper abdomen, lower abdomen, arm, thighs, upper back and lower back. A total mFG score of ≥≥8 has been used to define the presence of hirsutism. ,
All participants were asked to come to our clinic between the 2 nd and 5 th day of menses. Transvaginal and pelvic ultrasound was performed with Logiq 200 (GE Healthcare Medical Diagnostics, Little Chalfont, Buckinghamshire, United Kingdom) scanner in all participants.
After an overnight fast (8-12 h), venous blood was drawn from antecubital veins. The levels of routine hormonal parameters, including thyroid stimulating hormone, follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin, total testosterone (TT) and fasting serum insulin (FSI) were measured by Beckman Coulter DXI 600 ® analyzer using enzyme immunoassay kit (Beckman Coulter ® , USA 2007), sex hormone binding globulin (SHBG), dehydro-epiandrosterone sulfate (DHEA-S), 17 α OH-progesterone, androstenedione, TT and free testosterone (FT) were measured by enzyme-linked immunosorbent assay (ELISA) using Diametra ® kit (Diametra ® , Italy, 2009). Routine biochemical parameters including fasting plasma glucose (FPG), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TOT-C) were measured by Beckman Coulter DXI 600 ® analyzer using electrochemiluminescent immunoassay (ECLIA) kit (Beckman Coulter ® , USA 2007).
LH/FSH and FGP/FSI values were calculated and homeostasis model assessment-insulin resistance (HOMA-IR) index were calculated as (FPG [mg/dl] ×× FSI [μIU/ml]/405) for each woman. , All cases were screened with a 2-h 75-g oral glucose tolerance test.
Venous blood samples were drawn and collected into dry tubes. After the tubes had been allowed to clot at room temperature for 30 min, serum was separated immediately by centrifugation at 3780 rpm for 7 min at 4°C and stored at −80°C until being assayed. The frozen samples were melted at room temperature and then all samples were studied simultaneously by a single researcher in the same assay. Serum obestatin levels were measured by spectrophotometer (Bio-tek Instruments, Inc., Cal/USA) using a commercial ELISA kit (Uscn Life Human Obestatin, Wuhan, PRC, 2011).
All cases were consulted in nutrition and dietary unit, who were enrolled in 3 months diet plan for weight loss. Daily energy requirement (DER) to lose weight was calculated by using following the formula: DER = (Basal metabolic rate [BMR] × Physical activity factor) −500 kcal. BMR was calculated by using Scofield equation which has been commonly used in clinical trials.  Diets administered to the patients were individualized with respect to body weight, height, BMI, age, physical activity, degree of hormonal imbalance and daily eating habits of each case. All patients were on the carbohydrate-rich, fat-poor diet (55-60% carbohydrates, 12-15% protein and 25-30% fat).
All the statistical calculations were performed with the Statistical Package for Social Sciences (SPSS) for Windows (SPSS version 15.0; SPSS Inc., Chicago, IL) statistical software package. We used the Shapiro-Wilk test to test variables for normality. Mann-Whitney U-test was used for comparisons between PCOS and control groups. Wilcoxon signed rank test was used to compare the variables between baseline and after the diet in PCOS group. Results of descriptive analysis were presented as mean ± standard deviation. Degree of association between continuous variables was calculated by Spearman's rho correlation coefficient. In all statistical comparisons, a p ≤ 0.05 was used to indicate a significant difference.
| Results|| |
Polycystic ovary syndrome versus non-polycystic ovary syndrome before the diet
The amount of energy obtained by the diet, anthropometric, biochemical and hormonal measurements are shown in [Table 1]. Before the diet, two groups were similar in terms of daily amount of energy obtained from the diet, age, BFP and BMI. In PCOS group, TT levels, mFG scores, LH/FSH and waist to hip ratio (WHR) values were significantly higher than those in non-PCOS group. The progesterone levels measured between the 21 st and 24 th day of the menstrual cycle were significantly higher in PCOS group compared with non-PCOS group. There were no significant differences in FSH, LH, E2, prolactin, TT, SHBG, DHEA-S, androstenedione, FT, FSI, FPG, HOMA-IR, HDL-C, LDL-C and TOT-C between PCOS and non-PCOS groups. The mean TG level of PCOS group was higher than that of non-PCOS group. There is no statistically significant difference in obestatin levels between the groups.
|Table 1: Antrophometric, hormonal and biochemical parameters in PCOS and non-PCOS groups |
Click here to view
Before versus after the diet in polycystic ovary syndrome
Anthropometric and biochemical values before and after the diet in PCOS group are shown in [Table 2]. In PCOS group, weight, WHR, BFP, BMI, LH, LH/FSH and DHEA-S values after the diet were significantly lower than those before the diet. Obestatin value of PCOS group before the diet was slightly but not significantly lower than that of after the diet. Serum obestatin levels of the groups before and after the diet are shown in [Figure 1].
|Table 2: Antrophometric, hormonal and biochemical parameters in PCOS and non-PCOS groups before and after the diet |
Click here to view
|Figure 1. Obestatin levels in polycystic ovary syndrome (PCOS) and non-PCOS groups before and after diet|
Click here to view
Relationships of obestatin with antrophometric, biochemical and hormonal parameters
In PCOS group, although obestatin levels were negatively correlated with HDL-C levels, there was no significant correlation between obestatin and other biochemical and clinical parameters before the diet. After the diet, obestatin was only correlated (negatively) with WHR. In PCOS and non-PCOS groups, the relationships between obestatin and other parameters are given in [Table 3].
|Table 3: Relationships of antrophometric, hormonal and biochemical parameters with obestatin levels in PCOS and non-PCOS groups, before and after the diet |
Click here to view
| Discussion|| |
Obestatin is an anorectic peptide consisting of 23 amino acids and it is encoded by the same gene as ghrelin hormone.  Little is known about the effect of obestatin on reproductive system. In a recent study, it has been reported that obestatin can directly control functions of granulosa cells via stimulating proliferation and apoptosis of granulosa cells and progesterone secretion in pig ovaries.  With opposite effect to ghrelin, obestatin suppresses appetite and reduces food intake. , Obestatin excites vagal afferent fibers, which resulted in an increased sense of satiety and weight gain can be prevented. , In human studies, based on the finding that obestatin levels are higher in obese subjects compared to lean litter-mates suggests that the obestatin may have a role in the long-term regulation of body weight. ,
It has been determined that obestatin is closely related with metabolic parameters, obesity and insulin resistance, and it has been reported that obestatin level increases after weight loss.  Therefore, we investigated the effect of "carbohydrate-rich, fat-poor diet" on obestatin levels in obese and overweight subjects with PCOS. To our knowledge, this is the first study to investigate obestatin levels in subjects with PCOS.
In our study, WHR values were reduced, and menstrual irregularities improved in parallel to weight loss by nutritional intervention. Our findings that reduction in WHR values and improvement in menstrual functions by diet are congruent with the literature. ,,
Our findings showed that there was no relationship between the amount of energy obtained and serum obestatin levels. In a study by Huda et al., similar to our finding, it has been suggested that there was no change in obestatin level by food intake and obestatin level could not be changed, due to consuming carbohydrate-based meal. Diets comprised of various items may affect obestatin levels in a different manner. Lower levels of obestatin in obese subjects suggest that the obestatin may have a role in the body weight regulation.  However, in other studies, it has been reported that the amount of obtained energy may significantly change obestatin level. ,,,,,
In our study, we observed no correlation between obestatin levels with BMI and BFP. In a study on relationships of obestatin, ghrelin and obesity, it has been determined that ghrelin and obestatin levels in circulation were lower in obese subjects than those in lean litter-mates, ghrelin/obestatin ratio was increased after adjusting for age and gender and ghrelin/obestatin ratio was positively correlated with BMI.  In another study, it has been reported that obestatin levels in circulation were higher in obese women than those in controls; there was an inverse correlation between ghrelin/obestatin ratio and BMI when data from obese and lean women were evaluated together and there was no correlation between ghrelin/obestatin ratio and BMI in obese group which is congruent with our finding. 
In our study, WHR was lower in non-PCOS group compared to PCOS group. In PCOS group, while there was no correlation between WHR and obestatin prior to the diet, an inverse correlation was found between these parameters after the diet. Additionally, there was no significant correlation between obestatin and BMI. These findings as a whole suggest that central fat deposition in PCOS may play a key role.  There is a study showing that obestatin levels are inversely correlated with WHR in patients with type II DM and with glucose intolerance. 
In our study, there was no relationship between obestatin levels and insulin resistance. This finding is congruent with the findings as reported by some other authors. , In parallel to these findings, it has been reported by Lippl et al. that there was no significant difference in obestatin levels between patients with DM and patients without DM who were similar to DM group in terms of gender, BMI and insulin and in DM group, there was an inverse relationship between obestatin and insulin levels.  In another study including insulin-resistant and insulin-sensitive individuals, it has been determined that fasting plasma concentration of obestatin in patients without DM declined in the presence of insulin resistance and obestatin levels were positively correlated with insulin sensitivity.  In a study on relationships between plasma leptin and obestatin in obese, lean or anorexic subjects, Nakahara et al. have demonstrated that plasma obestatin levels were significantly lower and negatively correlated with BMI, plasma leptin, insulin and HOMA-IR in obese subjects. 
We found that obestatin levels increased after the diet compared to baseline values, but the increase is not significant in PCOS and non-PCOS groups. Studies report either an increase, decrease or no change in obestatin levels, after weight loss compared with baseline. Zou et al. have shown that obestatin levels were not different between obese and control groups; and ghrelin, obestatin and ghrelin/obestatin ratio increased after weight loss.  Obestatin levels have not revealed a significant change after weight loss in the study mentioned above and this finding is in parallel to our finding on obestatin. It has been determined that obestatin is closely associated with metabolic parameters, obesity and insulin resistance. It has been reported that the reason for the increase in obestatin level is negative feedback effect of obestatin on appetite. Reinehr et al. have reported that obestatin levels of adolescents with obesity were higher than those of adolescents with normal weight, and a significant increase occurred in obestatin level after weight loss. In this study, basal obestatin levels of adolescents who significantly lost weight were higher than those of adolescents with normal weight and were lower than those of adolescents who could not lose weight.  At the base of these findings, it has been suggested that obestatin level may be used to predict further development of obesity. Low levels of obestatin and high levels of ghrelin in obese subjects may be a result of adaptation to the increase in weight. While increment in ghrelin levels is resulting in body weight gain, obestatin are accepted to act as an antagonist of ghrelin.  Conversely, it had been reported that obestatin levels assessed before and 2 years after Roux-en-Y gastric bypass (RYGB) surgery in morbidly obese subjects remained stable after weight loss in long-term follow-up.  The authors have tried to explain lower long-term ghrelin levels and stable obestatin levels after RYGB procedure, with reduction in gastric volume and tissue, causing ingested nutrients to bypass the stomach, which did not allow an expected gastrointestinal hormone profile and/or with the reassessment of obestatin and ghrelin levels after a long period of 2 years.
In our study, when the correlations between lipid profile and obestatin were examined, we found that there was an inverse correlation between obestatin and HDL-C. In contrast to this finding, some of the authors have reported that obestatin infusions for a period of 8 days reduced amount of epididymal and perirenal adipose tissue and plasma lipid concentrations in mice. , Vicennati et al. have also reported that obestatin levels were positively correlated with TOT-C and TG levels.  Nagaraj et al. have reported that obestatin treatment for 8 days provides reduction in cholesterol (slight, approximately 2%) and TG levels (approximately 22%) in rats.  Same authors have found that cholesterol and TG levels were reduced by 13% and 32% respectively through obestatin treatment in rats.  Agnew et al. have observed that no change in food/fluid intake, body weight, plasma glucose and cholesterol levels, but 40% reduction in plasma TGs in rats chronically treated with a stable obestatin analog. 
We did not find statistically significant differences in obestatin levels before and after the diet for both groups. There was no correlation between obestatin levels with FSI, HOMA-IR and BMI values neither before nor after the diet. These findings suggest that distinct mechanisms play roles in the regulation of obestatin levels in case of high BMI. Similar levels of obestatin in both groups may be related to HOMA-IR and BMI, which have relatively close values between the groups and short period of diet in our study.
Our results did not clarify whether or not obestatin played a role in PCOS. The reason for this is that the sample size may not be large enough to evaluate obestatin levels in PCOS that is a heterogeneous condition both clinically and biochemically.
Results of the previous studies on relationships between obestatin with BMI, food intake, energy metabolism and insulin resistance are inconsistent and the mechanisms underlying these relationships remain unclear and; further large-scale, prospective and long-term studies are required to evaluate effects of obestatin in PCOS as a complex disease.
Conflict of interest: All of the authors have disclosed no financial relationship with a biotechnology manufacturer, a pharmaceutical company or other commercial entity that has an interest in the subject matter or materials discussed in the manuscript.
| References|| |
Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935;29:181-91.
Kiddy DS, Sharp PS, White DM, Scanlon MF, Mason HD, Bray CS, et al. Differences in clinical and endocrine features between obese and non-obese subjects with polycystic ovary syndrome: An analysis of 263 consecutive cases. Clin Endocrinol (Oxf) 1990;32:213-20.
Goldzieher JW, Green JA. The polycystic ovary. I. Clinical and histologic features. J Clin Endocrinol Metab 1962;22:325-38.
Kiddy DS, Hamilton-Fairley D, Bush A, Short F, Anyaoku V, Reed MJ, et al. Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome. Clin Endocrinol (Oxf) 1992;36:105-11.
Zhang JV, Ren PG, Avsian-Kretchmer O, Luo CW, Rauch R, Klein C, et al. Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake. Science 2005;310:996-9.
McDonough PG, Mahesh VB, Ellegood JO. Steroid, follicle-stimulating hormone, and luteinizing hormone profiles in identical twins with polycystic ovaries. Am J Obstet Gynecol 1972;113:1072-8.
Chanoine JP, Wong AC, Barrios V. Obestatin, acylated and total ghrelin concentrations in the perinatal rat pancreas. Horm Res 2006;66:81-8.
Dun SL, Brailoiu GC, Brailoiu E, Yang J, Chang JK, Dun NJ. Distribution and biological activity of obestatin in the rat. J Endocrinol 2006;191:481-9.
Carlini VP, Schiöth HB, Debarioglio SR. Obestatin improves memory performance and causes anxiolytic effects in rats. Biochem Biophys Res Commun 2007;352:907-12.
Nogueiras R, Pfluger P, Tovar S, Arnold M, Mitchell S, Morris A, et al. Effects of obestatin on energy balance and growth hormone secretion in rodents. Endocrinology 2007;148:21-6.
Samson WK, White MM, Price C, Ferguson AV. Obestatin acts in brain to inhibit thirst. Am J Physiol Regul Integr Comp Physiol 2007;292:R637-43.
Huda MS, Durham BH, Wong SP, Deepak D, Kerrigan D, McCulloch P, et al. Plasma obestatin levels are lower in obese and post-gastrectomy subjects, but do not change in response to a meal. Int J Obes (Lond) 2008;32:129-35.
Zamrazilová H, Hainer V, Sedlácková D, Papezová H, Kunesová M, Bellisle F, et al. Plasma obestatin levels in normal weight, obese and anorectic women. Physiol Res 2008;57 Suppl 1:S49-55.
Guo ZF, Zheng X, Qin YW, Hu JQ, Chen SP, Zhang Z. Circulating preprandial ghrelin to obestatin ratio is increased in human obesity. J Clin Endocrinol Metab 2007;92:1875-80.
Zou CC, Liang L, Wang CL, Fu JF, Zhao ZY. The change in ghrelin and obestatin levels in obese children after weight reduction. Acta Paediatr 2009;98:159-65.
Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 2004;89:2745-9.
Soares JB, Leite-Moreira AF. Ghrelin, des-acyl ghrelin and obestatin: Three pieces of the same puzzle. Peptides 2008;29:1255-70.
Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004;19:41-7.
Keys A, Fidanza F, Karvonen MJ. Indices of relative weight and obesity. J Chronic Dis 1972;25:329-43.
Deurenberg P, Weststrate JA, Seidell JC. Body mass index as a measure of body fatness: Age-and sex-specific prediction formulas. Br J Nutr 1991;65:105-14.
Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab 1961;21:1440-7.
Hatch R, Rosenfield RL, Kim MH, Tredway D. Hirsutism: Implications, etiology, and management. Am J Obstet Gynecol 1981;140:815-30.
Crowther NJ, Ferris WF, Ojwang PJ, Rheeder P. The effect of abdominal obesity on insulin sensitivity and serum lipid and cytokine concentrations in African women. Clin Endocrinol (Oxf) 2006;64:535-41.
Sivan E, Homko CJ, Chen X, Reece EA, Boden G. Effect of insulin on fat metabolism during and after normal pregnancy. Diabetes 1999;48:834-8.
Schofield WN. Predicting basal metabolic rate, new standards and review of previous work. Hum Nutr Clin Nutr 1985;39 Suppl 1:5-41.
Mészárosová M, Sirotkin AV, Grossmann R, Darlak K, Valenzuela F. The effect of obestatin on porcine ovarian granulosa cells. Anim Reprod Sci 2008;108:196-207.
Kohrt WM, Kirwan JP, Staten MA, Bourey RE, King DS, Holloszy JO. Insulin resistance in aging is related to abdominal obesity. Diabetes 1993;42:273-81.
Clark AM, Thornley B, Tomlinson L, Galletley C, Norman RJ. Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum Reprod 1998;13:1502-5.
Huber-Buchholz MM, Carey DG, Norman RJ. Restoration of reproductive potential by lifestyle modification in obese polycystic ovary syndrome: Role of insulin sensitivity and luteinizing hormone. J Clin Endocrinol Metab 1999;84:1470-4.
Egido EM, Hernández R, Marco J, Silvestre RA. Effect of obestatin on insulin, glucagon and somatostatin secretion in the perfused rat pancreas. Regul Pept 2009;152:61-6.
Chartrel N, Alvear-Perez R, Leprince J, Iturrioz X, Reaux-Le Goazigo A, Audinot V, et al. Comment on "Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake". Science 2007;315:766.
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.
Kim SH, Abbasi F, Reaven GM. Impact of degree of obesity on surrogate estimates of insulin resistance. Diabetes Care 2004;27:1998-2002.
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;66:593-7.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412-9.
Lippl F, Erdmann J, Lichter N, Tholl S, Wagenpfeil S, Adam O, et al. Relation of plasma obestatin levels to bmi, gender, age and insulin. Horm Metab Res 2008;40:806-12.
Unniappan S, Speck M, Kieffer TJ. Metabolic effects of chronic obestatin infusion in rats. Peptides 2008;29:1354-61.
Nakahara T, Harada T, Yasuhara D, Shimada N, Amitani H, Sakoguchi T, et al. Plasma obestatin concentrations are negatively correlated with body mass index, insulin resistance index, and plasma leptin concentrations in obesity and anorexia nervosa. Biol Psychiatry 2008;64:252-5.
Reinehr T, de Sousa G, Roth CL. Obestatin and ghrelin levels in obese children and adolescents before and after reduction of overweight. Clin Endocrinol (Oxf) 2008;68:304-10.
Roth CL, Reinehr T, Schernthaner GH, Kopp HP, Kriwanek S, Schernthaner G. Ghrelin and obestatin levels in severely obese women before and after weight loss after Roux-en-Y gastric bypass surgery. Obes Surg 2009;19:29-35.
Nagaraj S, Peddha MS, Manjappara UV. Fragments of obestatin as modulators of feed intake, circulating lipids, and stored fat. Biochem Biophys Res Commun 2008;366:731-7.
Nagaraj S, Peddha MS, Manjappara UV. Fragment analogs as better mimics of obestatin. Regul Pept 2009;158:143-8.
Agnew A, Calderwood D, Chevallier OP, Greer B, Grieve DJ, Green BD. Chronic treatment with a stable obestatin analog significantly alters plasma triglyceride levels but fails to influence food intake; fluid intake; body weight; or body composition in rats. Peptides 2011;32:755-62.
[Table 1], [Table 2], [Table 3]