QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Geliebter, A. Articles by Hashim, S. A. Search for Related Content PubMed PubMed Citation Articles by Geliebter, A. Articles by Hashim, S. A.

---

Symposium: Ghrelin: Its Role in Energy Balance

Plasma Ghrelin Concentrations Are Lower in Binge-Eating Disorder^1,2,3

Departments of Medicine and Psychiatry, New York Obesity Research Center, St. Luke’s Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, NY

⁴To whom correspondence should be addressed. E-mail: ag58{at}columbia.edu.

	ABSTRACT

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
Binge-eating disorder (BED), characterized by binge meals without purging afterward, is found in about 30% of obese individuals seeking treatment. The study objective was to ascertain abnormalities in hormones influencing appetite in BED, especially ghrelin, an appetite-stimulating peptide, which was expected to be elevated. Measurements were made of plasma insulin, leptin, glucagon, cholecystokinin, and ghrelin, as well as glucose following an overnight 12-h fast, prior to and after ingestion (from 0 to 5 min) of a nutritionally complete liquid meal (1254 kJ) at 0830 h, at –15, 0, 5, 15, 30, 60, 90, and 120 min. Appetite ratings including hunger and fullness were also obtained. An acetaminophen tracer was used to assess gastric emptying rate. Three groups of comparably obese women (BMI = 35.9 ± 5.5; % body fat = 44.9 ± 4.7) participated: 12 nonbinge eating normals (NB), 14 subthreshold BED, and 11 BED. The BED subjects, compared to NB subjects, had lower baseline ghrelin concentrations prior to the meal, a lower area under the curve (AUC), with lower levels at 5, 15, 30, 90, and 120 min, and a smaller decline in ghrelin postmeal (all P < 0.03). The other blood values did not differ among groups, and neither did gastric emptying rate nor ratings of fullness. The BED subjects were then randomly assigned to treatment with cognitive-behavior therapy and diet (n = 5) or to a wait-list control (n = 4). Baseline ghrelin (P = 0.01) and AUC increased (P = 0.02), across both conditions, in which most subjects (7 of 9) stopped binge eating. The lower fasting and postmeal plasma ghrelin levels in BED are consistent with lower ghrelin levels in obese compared to lean individuals and suggests downregulation by binge eating.

KEY WORDS: • obesity • peptide hormones • satiety • ghrelin • binge eating • leptin • CCK • insulin • glucagon

The prevalence of obesity, associated with chronic diseases such as diabetes and heart disease, continues to increase globally, especially in the United States (1), where it has reached epidemic proportions (2). Obesity is highly resistant to treatment, with most lost weight regained within 5 y after dieting (3,4). About 30% of obese subjects who participate in weight loss programs have binge-eating disorder (BED)⁵ (5). They overeat (objectively large amounts) at least twice a week for 6 mo with a sense of loss of control, but do not purge afterward, as do patients with bulimia nervosa (BN), who are usually of normal weight. BED, characterized relatively recently, is listed in the Appendix of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association (6). With the rising epidemic of obesity, BED prevalence is also increasing, lending urgency to the study of its pathogenesis. There is evidence of a biological basis for BED, including moderate heritability of 0.50 (7), possible association with melanocortin 4 receptor mutation (8), and an enlarged stomach capacity (9).

Peripheral hormones that influence food intake also may play a role in BED. These hormones induce satiety signals that act directly on the brain or indirectly via the vagus nerve or by slowing gastric emptying (10). Such appetite-influencing hormones include insulin, leptin, glucagon, and cholecystokinin (CCK), the levels of which rise after meals and which suppress food intake when administered peripherally (10,11) or centrally (10). In BN, slower gastric emptying has been reported (12,13), decreasing the duodenal release of the anorexigenic peptide CCK (13,14), which may contribute to the binge eating. We have proposed that slower gastric emptying following a fixed liquid meal in BN (12) and BED (9) is associated with a larger gastric capacity, which results in a smaller rise in intragastric pressure and, hence, diminished driving force for emptying (12,15). Gastric emptying of a liquid meal can be assessed with the tracer acetaminophen (paracetamol), which is rapidly absorbed from the duodenum after leaving the stomach and correlates well with radiolabeling and intragastric suction (16). Leptin, which is secreted mainly by adipose tissue, is higher in obese than in lean individuals and decreases during weight and fat loss (17). In one report, leptin was higher in BED patients compared to controls (18).

Ghrelin is a recently discovered peripheral peptide hormone that stimulates food intake (19). Ghrelin is produced mainly by the stomach and, when administered, increases food intake in animals (20) and humans, without altering human gastric emptying, as assessed by acetaminophen (21). Ghrelin rises before and falls following meals (22).

This study was undertaken to test the hypotheses that obese BED subjects have higher fasting and postprandial ghrelin levels, as well as a slower gastric emptying rate, and therefore lower postprandial CCK, than non-BED obese controls.

	SUBJECTS AND METHODS

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
Subjects

We recruited 38 overweight and obese women (BMI > 27) and classified them into 3 groups: 12 nonbinge eating (NB), 14 binge eating but not meeting full criteria (BE), and 11 BED (full-fledged syndrome), assessed with the Questionnaire on Eating and Weight Patterns (5) and confirmed by clinical interview. The 3 groups did not differ on level of education, race, or ethnicity. Except for their weight, the subjects were all healthy as revealed by a medical history and physical examination, including electrocardiogram and blood chemistry. They were all premenopausal, nonsmokers, and weight stable within ±3.5% in the past 3 mo. Exclusions included use of illegal drugs or any medications that could affect body weight. All subjects signed an informed consent form, which had been approved by the St. Luke’s-Roosevelt Institutional Review Board. The characteristics of the participants are shown in Table 1.

All procedures were performed following a 12-h overnight fast after a usual dinner completed by 0830 h. They included measures of body composition on 1 day and hormones and gastric emptying on another day, at least 2 d apart.

    Body composition. Air displacement plethysmography (BODPOD; Life Measurement Instrument) was used to determine body fat. Density from air displacement correlates well with underwater weighing (23) and has a CV of 0.7%.

    Appetite hormones and gastric emptying. A butterfly needle, attached by catheter to a normal saline bag containing heparin (0.1%), was inserted into a forearm vein at 0730 h. The subject was allowed to adapt for 30 min prior to the baseline blood draws at 0800 and 0815 h. The 600-mL meal (300 mL Boost; 300 mL water), a complete nutritional meal (Mead Johnson) providing 1254 kJ, was composed of 24% protein (19 g), 55% carbohydrate (41 g, including 20 g sugar), and 21% fat (6 g). The meal was consumed in 5 min at a constant rate from a graduated beaker. The liquid meal contained 1.5 g of acetaminophen as a tracer for gastric emptying (16). Ratings of appetite, including hunger and fullness, were made by the subject on a visual analogue scale from 0 to 100 just before each blood draw. Blood samples were drawn on the following schedule:

The blood samples were added to tubes containing EDTA and aprotinin (Trasylol), which were inverted gently 4 times, kept on ice for a few minutes, and then cold centrifuged for 15 min to obtain plasma, which was stored in labeled cryomicrotubes at –80°C until assayed. Measurements were made of glucose, acetaminophen, insulin, leptin, glucagon, CCK, and ghrelin by our Hormone and Metabolite Laboratory. All assays were performed in duplicate. Glucose was assayed with a Beckman glucose analyzer (glucose oxidase method), acetaminophen was assayed (intra-assay CV = 2.1%) with a colorimetric kit (after spiking with 0.1 mL of 50 mg/L of acetaminophen standard from Sigma) by UV spectrophotometer (Perkin-Elmer) to assess gastric emptying rate from time to peak value and area under the curve (AUC) (16), insulin with an RIA kit from Linco (intra-assay CV = 4.4, interassay CV = 5.4), glucagon with an RIA kit (DPC method) from Linco (intra-assay CV = 3.8, interassay = 9.9), leptin with an RIA kit from Linco (intra-assay CV = 5.3, interassay CV = 7.3), CCK with an RIA kit from ALPCO (intra-assay CV = 3.8, interassay CV = 4.6), and ghrelin with an RIA kit from Phoenix (intra-assay CV = 2.7, interassay = 3.2). Insulin resistance was estimated from homeostasis model assessment [fasting plasma glucose (micromoles per liter) x fasting insulin (microunits per milliliter) insulin]/22.5). The AUC for hormones and glucose was obtained after interpolating for missing blood concentration data, which composed <2% of the total, within a given subject. One NB and 1 BE subject did not complete all blood tests.

    Treatment. Ten of the 11 BED subjects were then randomized for 6 wk to either (a) treatment with cognitive behavior therapy and diet (R-Kane formula diet providing 3762 kJ/d), the standard treatment for overweight BED subjects (24), with individual weekly visits (n = 5) or (b) a nontreatment wait-list control (n = 5). One subject dropped out of the wait-list group. The test meal protocol was repeated after the intervention.

    Data analysis. General Linear Model (GLM) ANOVA followed by Tukey’s HSD post hoc tests were used to analyze characteristics of the groups and test meal–related blood concentrations for the baseline (mean of –15 and 0 min), AUC (calculated by the trapezoidal method), gastric emptying rate based on the time to the peak value and the AUC for acetaminophen, and the AUC for appetite ratings. If the AUC for concentrations or ratings revealed important group differences, MANOVA followed by Tukey’s HSD post hoc tests were used to analyze specific time points. Serial blood concentrations and ratings were also analyzed by GLM repeated measures for changes over time and interactions among BED groups. Stepwise multiple regression was performed to relate AUC for hormones with AUC for fullness rating. Pearson’s r correlations were determined for selected variables. Two-tailed P 0.05 was required for significance. The statistical analyses were performed using SPSS version 11.5.

	RESULTS

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
Weight, BMI, and percentage body fat did not differ among groups (Table 1). In relation to the test meal, fasting or AUC for glucose, insulin, leptin, glucagon, CCK, or ratings of appetite did not differ among groups (Table 2). Gastric emptying rate did not differ by time to peak value for acetaminophen, F (2,35) = 1.22, P = 0.31 (for NB (±SEM): 103.8 ± 5.5 min, for BE: 96.4 ± 6.4, and for BED: 109.1 ± 4.6 min) or by AUC for acetaminophen, F (2,35) = 1.87, P = 0.17, ns (Table 2). Insulin resistance did not differ between groups, F (2,34) = 1.7, P = 0.20, ns.

View larger version (24K): [in this window] [in a new window]   FIGURE 1 Plasma concentrations of ghrelin, CCK, leptin, and ratings of fullness and hunger prior to and following a fixed test meal, ingested from 0 to 5 min, in obese subjects with BED, with BE, and with NB. Top panel: Fasting plasma ghrelin and AUC for plasma ghrelin levels were smaller, and the postprandial decline in ghrelin was smaller (P 0.05) in BED than in NB. Ghrelin levels for BE were intermediate and did not differ from either group. (To convert to pmol/L, multiply by 0.296.) Second panel: Fasting and AUC for plasma CCK levels did not differ among the 3 groups of obese subjects. Third panel: Fasting and AUC for leptin levels did not differ between groups and showed an acute rise from 0 to 5 min across groups, P = 0.03. (To convert to nmol/L, multiply by 0.08.) Fourth panel: Fasting and AUC for fullness ratings did not differ among groups. Bottom panel: Fasting and AUC for hunger ratings did not differ among groups.

Following the intervention in the BED subjects, when ghrelin was reexamined there was an increase (F (1,7) = 7.8, P = 0.03) in fasting baseline ghrelin (±SEM) from 350 ± 36 to 587 ± 67 ng/L, with no difference between treated and untreated groups, F (1,7) = 1.8, P = 0.22, ns. Likewise, there was an increase, F (1,7) = 8.75, P = 0.02, in AUC for ghrelin from 39,298 pg/mL · min ± 3693 to 68,315 pg/mL · min ± 8340, with no difference between treated and untreated groups, F (1,7) = 1.4, P = 0.27. The weight change in both groups combined of –1.5 kg ± 3.9 had no impact on the ghrelin baseline change, F (1,6) = 0.01, P = 0.94, ns, or on the ghrelin AUC change, F (1,6) = 0.03, P = 0.88, ns. Closer examination showed that all 5 treated BED subjects remitted with absence of binge eating, and 2 of the 4 wait-listed BED subjects also remitted. When remission status was entered as a covariate, the change in baseline ghrelin, F (1,6) = 0.00, P = 1.0, ns, and the change in AUC for ghrelin were no longer significant, F (1,6) = 0.27, P = 0.62, ns.

	DISCUSSION

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
Lower fasting baseline ghrelin levels in overweight and obese BED subjects is counterintuitive because ghrelin, a peptide that stimulates hunger, was expected to be higher. The finding is buttressed by the intermediate fasting ghrelin levels in the subthreshold BE group. The fasting ghrelin values for the obese NB group fell in the range of levels reported in comparably obese subjects (22,25,26). The lower fasting ghrelin level in BED suggests that binge eating may downregulate ghrelin. Indeed, binge eating may occur in the absence of hunger (6), consistent with low ghrelin levels. These results complement the finding that fasting ghrelin is 27% lower in obese than in lean individuals (25), with the exception of Prader-Willi patients, who have elevated values (27,28). The lower ghrelin level in obesity may be a secondary response to overeating (25), possibly a conditioned response, rather than a primary causal factor (29). Even if ghrelin is not a primary factor, a ghrelin antagonist may still help to reduce food intake in obesity (30).

At the other end of the weight spectrum, in anorexia nervosa (AN), fasting ghrelin is highest (31). The elevated ghrelin in AN is consistent with ghrelin rising in animals to motivate feeding during starvation. In the middle of the weight spectrum, in lean patients with bulimia nervosa, who purge by vomiting, there are 2 recent inconsistent reports of similar or higher levels of fasting ghrelin (32,33) compared to controls.

Following the fixed meal, ghrelin also declined less in BED than NB from a lower baseline. This extends the recent finding of a smaller postprandial fall in ghrelin from a lower baseline in obese than in lean subjects (26). The magnitude of the fall in ghrelin may itself be a signal for satiation, which would be weaker with a smaller decline in ghrelin, as also suggested by a recent report of blunted decline in ghrelin after a meal in BN individuals (33). The differences in ghrelin levels in the BED and NB groups were not related to differences in body fat because body composition did not differ between these groups. The ghrelin differences between the BED and the NB groups were more than twice the magnitude of the change observed in obese subjects prior to and following substantial weight loss, when ghrelin increases (22).

The low ghrelin values in the BED subjects were nevertheless much higher than the low values in severely obese patients following gastric bypass surgery (22), and in both of these patient groups, ghrelin is not very responsive to meals (22). The smaller fall in ghrelin we observed is unlikely to represent a floor effect from a lower baseline, because some of the individual values of ghrelin fell much lower than the means shown in Figure 1 to <100 pg/ml but still within the sensitivity of the assay. Following remission of BED, which occurred in all those in the treated group and in half the wait-list group, there was an increase in AUC for ghrelin toward the normal state, bolstering the findings of an association of the disorder with the ghrelin abnormality. This increase in ghrelin could help thwart the recovering BED patient. In any case, this observed increase in plasma ghrelin in a small sample needs to be confirmed in a larger group of treated BED subjects.

The results also showed that BED individuals did not have slower gastric emptying after a fixed meal, and consistent with this, CCK levels were not lower postprandially, unlike the findings in BN (13,14). Although a large gastric capacity has been associated with slower emptying, capacity was not as large in BED as in BN individuals (9) and may not be large enough to lead to substantially slower emptying and a greater delay in the release of CCK (34).

We did not observe substantially higher fasting leptin in BED as in one previous report (18), but our results are consistent with another report demonstrating no difference in leptin levels (35). We did observe an acute rise in leptin just after the meal across all subjects, which is the first report to our knowledge of such a short-term rise in leptin after a meal in humans, although it did not correlate with changes in fullness. Generally, a delay of several hours is needed before leptin increases after a meal. This acute rise may be related to leptin released by the stomach, a recently discovered additional source of leptin besides the adipose tissue (36,37). Few studies have examined leptin changes this soon after a meal. The meal was also relatively high in carbohydrate (55%), which is known to stimulate leptin more than fat (38).

Although the AUC for the appetite ratings among the groups did not differ, the pattern was in the direction expected of less fullness after the same-size meal in the BED subjects. Indeed, in previous studies, when BED subjects were requested to consume a meal until extremely full, they ingested much larger meals than non-BED subjects (39). We found an inverse substantial correlation across groups between fullness and ghrelin, the only hormone of those measured to show a significant relation. The study, however, concerned a limited number of hormones, and other hormones involved in appetite mechanisms, such as peptide YY3–36 (40) glucagon-like peptide-1 (10), and amylin (41), were not examined.

In conclusion, BED subjects had lower ghrelin levels premeal, which then declined only slightly postmeal. The lower fasting ghrelin may be due to down regulation by binge eating, and the smaller decline in ghrelin following the meal may then provide a weaker satiety signal. The lower fasting and postprandial concentrations of ghrelin, a key hormone influencing food intake and appetite, may thus be related to the pathophysiology of BED.

	ACKNOWLEDGMENTS

	FOOTNOTES

 
¹ Presented as part of the symposium "Ghrelin: Its Role in Energy Balance" given at the 2004 Experimental Biology meeting on April 19, 2004, Washington, DC. The symposium was sponsored by the American Society for Nutritional Sciences and in part by Abbott Laboratories, Linco Research, Inc., and Merck Research Laboratories. The proceedings are published as a supplement to The Journal of Nutrition. This supplement is the responsibility of the Guest Editors to whom the Editor of The Journal of Nutrition has delegated supervision of both technical conformity to the published regulations of The Journal of Nutrition and general oversight of the scientific merit of each article. The opinions expressed in this publication are those of the authors and are not attributable to the sponsors or the publisher, editor, or editorial board of The Journal of Nutrition. The views expressed herein are those of the authors and do not necessarily reflect those of Abbott Laboratories, Linco Research, Inc., and Merck Research Laboratories. The Guest Editors for the symposium publication are Gary E. Truett, Department of Nutrition, Knoxville, TN, and Elizabeth J. Parks, University of Minnesota, St. Paul, MN.

² The NY Obesity Research Center (DK 26687) performed body composition services and hormone assays. The General Clinical Research Center provided supplies, nursing services, and clinical space (MO1 RR0064529). The study was supported by National Institutes of Health Grant DK54318 to A.G. We are grateful to Mead Johnson and R-Kane Products for providing formula diets.

³ Preliminary hormone data were previously published (34).

⁵ Abbreviations used: AN, anorexia nervosa; AUC, area under the curve; BE, subthreshold BED; BED, binge-eating disorder; BN, bulimia nervosa; NB, non-binge eater; CCK, cholecystokinin; GLM, General Linear Model.

	LITERATURE CITED

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 

1. Flegal, K. M., Carroll, M. D., Ogden, C. L. & Johnson, C. L. (2002) Prevalence and trends in obesity among US adults, 1999–2000. J. Am. Med. Assoc. 288:1723-1727.[Abstract/Free Full Text]

2. Hill, J. O. & Peters, J. C. (1998) Environmental contributions to the obesity epidemic. Science 280:1371-4.[Abstract/Free Full Text]

3. Foster, G. D., Wadden, T. A., Kendall, P. C., Stunkard, A. J. & Vogt, R. A. (1996) Psychological effects of weight loss and regain: A prospective evaluation. J. Consult. Clin. Psychol. 64:752-757.[Medline]

4. Yanovski, S. Z. & Yanovski, J. A. (2002) Obesity. N. Engl. J. Med. 346:591-602.[Free Full Text]

5. Yanovski, S. Z. (1993) Binge eating disorder: current knowledge and future directions. Obes. Res. 1:306-318.[Medline]

6. American Psychiatric Association (2000) Diagnostic and Statistical Manual of Mental Disorders 4th ed., Text Revision ed. 2000 Washington, DC.

7. Bulik, C. M., Sullivan, P. F. & Kendler, K. S. (2003) Genetic and environmental contributions to obesity and binge eating. Int. J. Eat. Disord. 33:293-298.[Medline]

8. Branson, R., Potoczna, N., Kral, J. G., Lentes, K. U., Hoehe, M. R. & Horber, F. F. (2003) Binge eating as a major phenotype of melanocortin 4 receptor gene mutations. N. Engl. J. Med. 348:1096-1103.[Abstract/Free Full Text]

9. Geliebter, A. & Hashim, S. A. (2001) Gastric capacity in normal, obese, and bulimic women. Physiol. Behav. 74:743-746.[Medline]

10. Hellstrom, P. M., Geliebter, A., Naslund, E., Schmidt, P. T., Yahav, E., Hashim, S. A. & Yeomans, M. R. (2004) Peripheral and central signals in control of eating in normal, obese and binge-eating subjects. Br. J. Nutr. 92:547-557.

11. Kissileff, H. R., Carretta, J. C., Geliebter, A. & Pi-Sunyer, F. X. (2003) Cholecystokinin and stomach distension combine to reduce food intake in humans. Am. J. Physiol. Regul. Integr. Comp. Physiol. 285:R992-R998.[Abstract/Free Full Text]

12. Geliebter, A., Melton, P. M., McCray, R. S., Gallagher, D. R., Gage, D. & Hashim, S. A. (1992) Gastric capacity, gastric emptying, and test-meal intake in normal and bulimic women. Am. J. Clin. Nutr. 56:656-661.[Abstract/Free Full Text]

13. Devlin, M. J., Walsh, B. T., Guss, J. L., Kissileff, H. R., Liddle, R. A. & Petkova, E. (1997) Postprandial cholecystokinin release and gastric emptying in patients with bulimia nervosa. Am. J. Clin. Nutr. 65:114-120.[Abstract/Free Full Text]

14. Geracioti, T. D., Jr & Liddle, R. A. (1988) Impaired cholecystokinin secretion in bulimia nervosa. N. Engl. J. Med. 319:683-688.[Abstract]

15. Geliebter, A., Westreich, S., Pierson, R. N., Jr & Van Itallie, T. B. (1986) Extra-abdominal pressure alters food intake, intragastric pressure, and gastric emptying rate. Am. J. Physiol. 250:R549-R552.[Medline]

16. Näslund, E., Bogefors, J., Grybäck, P., Jacobsson, H. & Hellström, P. M. (2000) Gastric emptying: Comparison of scintigraphic, polyethylene glycol dilution, and paracetamol tracer assessment techniques. Scand. J. Gastroenterol. 35:375-379.[Medline]

17. Friedman, J. M. (2002) The function of leptin in nutrition, weight, and physiology. Nutr. Rev. 60:S1-S14.

18. Adami, G. F., Campostano, A., Cella, F. & Scopinaro, N. (2002) Serum leptin concentration in obese patients with binge eating disorder. Int. J. Obes. Relat. Metab. Disord. 26:1125-1128.[Medline]

19. Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H. & Kangawa, K. (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402:656-660.[Medline]

20. Tschop, M., Smiley, D. L. & Heiman, M. L. (2000) Ghrelin induces adiposity in rodents. Nature 407:908-913.[Medline]

21. Wren, A. M., Seal, L. J., Cohen, M. A., Brynes, A. E., Frost, G. S., Murphy, K. G., Dhillo, W. S., Ghatei, M. A. & Bloom, S. R. (2001) Ghrelin enhances appetite and increases food intake in humans. J. Clin. Endocrinol. Metab. 86:5992-5995.[Abstract/Free Full Text]

22. Cummings, D. E., Weigle, D. S., Frayo, R. S., Breen, P. A., Ma, M. K., Dellinger, E. P. & Purnell, J. Q. (2002) Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N. Engl. J. Med. 346:1623-1630.[Abstract/Free Full Text]

23. Demerath, E. W., Guo, S. S., Chumlea, W. C., Towne, B., Roche, A. F. & Siervogel, R. M. (2002) Comparison of percent body fat estimates using air displacement plethysmography and hydrodensitometry in adults and children. Int. J. Obes. Relat. Metab. Disord. 26:389-397.[Medline]

24. Wilfley, D. E. & Cohen, L. R. (1997) Psychological treatment of bulimia nervosa and binge eating disorder. Psychopharmacol. Bull. 33:437-454.[Medline]

25. Tschop, M., Weyer, C., Tataranni, P. A., Devanarayan, V., Ravussin, E. & Heiman, M. L. (2001) Circulating ghrelin levels are decreased in human obesity. Diabetes 50:707-709.[Abstract/Free Full Text]

26. English, P. J., Ghatei, M. A., Malik, I. A., Bloom, S. R. & Wilding, J. P. (2002) Food fails to suppress ghrelin levels in obese humans. J. Clin. Endocrinol. Metab. 87:2984.[Abstract/Free Full Text]

27. DelParigi, A., Tschop, M., Heiman, M. L., Salbe, A. D., Vozarova, B., Sell, S. M., Bunt, J. C. & Tataranni, P. A. (2002) High circulating ghrelin: a potential cause for hyperphagia and obesity in Prader-Willi syndrome. J. Clin. Endocrinol. Metab. 87:5461-5464.[Abstract/Free Full Text]

28. Cummings, D. E., Clement, K., Purnell, J. Q., Vaisse, C., Foster, K. E., Frayo, R. S., Schwartz, M. W., Basdevant, A. & Weigle, D. S. (2002) Elevated plasma ghrelin levels in Prader Willi syndrome. Nat. Med. 8:643-644.[Medline]

29. Geliebter, A. (2002) Weight loss and plasma ghrelin levels. N. Engl. J. Med. 347:1379-1381.[Free Full Text]

30. Asakawa, A., Inui, A., Kaga, T., Katsuura, G., Fujimiya, M., Fujino, M. A. & Kasuga, M. (2003) Antagonism of ghrelin receptor reduces food intake and body weight gain in mice. Gut 52:947-952.[Abstract/Free Full Text]

31. Shiiya, T., Nakazato, M. & Mizuta, M., et al (2002) Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J. Clin. Endocrinol. Metab. 87:240-244.[Abstract/Free Full Text]

32. Tanaka, M., Naruo, T., Nagai, N., Kuroki, N., Shiiya, T., Nakazato, M., Matsukura, S. & Nozoe, S. (2003) Habitual binge/purge behavior influences circulating ghrelin levels in eating disorders. J. Psychiatr. Res. 37:17-22.[Medline]

33. Monteleone, P., Martiadis, V., Fabrazzo, M., Serritella, C. & Maj, M. (2003) Ghrelin and leptin responses to food ingestion in bulimia nervosa: implications for binge-eating and compensatory behaviours. Psychol. Med. 33:1387-1394.[Medline]

34. Geliebter, A., Yahav, E., Gluck, M. E. & Hashim, S. A. (2004) Gastric capacity, test meal intake, and appetitive hormones in binge eating disorder. Physiol. Behav. 81:735-740.[Medline]

35. Karhunen, L., Haffner, S., Lappalainen, R., Turpeinen, A., Miettinen, H. & Uusitupa, M. (1997) Serum leptin and short-term regulation of eating in obese women. Clin. Sci. 92:573-578.[Medline]

36. Pico, C., Oliver, P., Sanchez, J. & Palou, A. (2003) Gastric leptin: a putative role in the short-term regulation of food intake. Br. J. Nutr. 90:735-741.[Medline]

37. Bado, A., Levasseur, S., Attoub, S., Kermorgant, S., Laigneau, J. P., Bortoluzzi, M. N., Moizo, L., Lehy, T., Guerre-Millo, M., Le Marchand-Brustel, Y. & Lewin, M. J. (1998) The stomach is a source of leptin. Nature 394:790-793.[Medline]

38. Romon, M., Lebel, P., Velly, C., Marecaux, N., Fruchart, J. C. & Dallongeville, J. (1999) Leptin response to carbohydrate or fat meal and association with subsequent satiety and energy intake. Am. J. Physiol. 277:E855-E861.

39. Geliebter, A., Hassid, G. & Hashim, S. A. (2001) Test meal intake in obese binge eaters in relation to mood and gender. Int. J. Eat. Disord. 29:488-494.[Medline]

40. Batterham, R. L., Cohen, M. A., Ellis, S. M., Le Roux, C. W., Withers, D. J., Frost, G. S., Ghatei, M. A. & Bloom, S. R. (2003) Inhibition of food intake in obese subjects by peptide YY3–36. N. Engl. J. Med. 349:941-948.[Abstract/Free Full Text]

41. Reda, T. K., Geliebter, A. & Pi-Sunyer, F. X. (2002) Amylin, food intake, and obesity. Obes. Res. 10:1087-1091.[Medline]

This article has been cited by other articles:

				A. Geliebter, C. N. Ochner, and R. Aviram-Friedman Appetite-Related Gut Peptides in Obesity and Binge Eating Disorder American Journal of Lifestyle Medicine, July 1, 2008; 2(4): 305 - 314. [Abstract] [PDF]

				C. L Pelkman, J. L Navia, A. E Miller, and R. J Pohle Novel calcium-gelled, alginate-pectin beverage reduced energy intake in nondieting overweight and obese women: interactions with dietary restraint status Am. J. Clinical Nutrition, December 1, 2007; 86(6): 1595 - 1602. [Abstract] [Full Text] [PDF]

				M. C Mirch, J. R McDuffie, S. Z Yanovski, M. Schollnberger, M. Tanofsky-Kraff, K. R Theim, J. Krakoff, and J. A Yanovski Effects of binge eating on satiation, satiety, and energy intake of overweight children. Am. J. Clinical Nutrition, October 1, 2006; 84(4): 732 - 738. [Abstract] [Full Text] [PDF]

				G. E. Truett and E. J. Parks Ghrelin: Its Role in Energy Balance J. Nutr., May 1, 2005; 135(5): 1313 - 1313. [Full Text] [PDF]

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Geliebter, A. Articles by Hashim, S. A. Search for Related Content PubMed PubMed Citation Articles by Geliebter, A. Articles by Hashim, S. A.