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Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-1319
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The Journal of Clinical Endocrinology & Metabolism Vol. 92, No. 5 1623-1629
Copyright © 2007 by The Endocrine Society

Hormonal and Psychological Factors Linked to the Increased Thermic Effect of Food in Malnourished Fasting Anorexia Nervosa

Daniel Rigaud, Bruno Verges, Nicole Colas-Linhart, Anne Petiet, Myriam Moukkaddem, Virginie Van Wymelbeke and Laurent Brondel

Centre Européen des Sciences du Goût (D.R., V.V.W., L.B.), Unité Mixte de Recherche-Centre National de la Recherche Scientifique 5170, 21000 Dijon, France; Centre Hospitalier Universitaire Le Bocage (B.V., M.M.), 21079 Dijon, France; and Faculty of Medicine X. Bichat (N.C.-L., A.P.), 75018 Paris, France

Address all correspondence and requests for reprints to: Prof. Daniel Rigaud, Service d’Endocrinologie et Nutrition, Hôpital Centre Hospitalier Universitaire Le Bocage, 21079 Dijon Cedex, France. E-mail: daniel.rigaud{at}chu-dijon.fr.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Objectives: In patients with anorexia nervosa (AN), weight gain is lower than that expected from the energy content of the meals. Thus we investigated the thermic effect of food (TEF) in relation to subjective feelings and plasma hormone levels in a group of AN patients.

Methods: TEF, feelings (14 items), and plasma release of ß-endorphin, ACTH, cortisol, dopamine, and catecholamines were evaluated in 15 AN patients (body mass index, 13.6 ± 1.2 kg·m–2) and in 15 healthy women after three gastric loads (0, 300, 700 kcal) infused by a nasogastric tube in a blind design.

Results: In AN, the blind loads induced an energy-dependent increase in TEF (P < 0.001), which was higher than that observed in healthy women (P < 0.001). Only in AN, a load-dependent decline in the high basal plasma level of ß-endorphin (P < 0.01), an increase in plasma ACTH (P < 0.02) after the two caloric loads, and an increase in cortisol, norepinephrine, and dopamine levels after the 700-kcal load only (P < 0.05) were noted. A calorie-dependent (P < 0.001) increase in nausea, abdominal discomfort, and fear of being fat ratings and a decrease in liking to eat (P < 0.001) and body image were observed in AN patients (P < 0.05). TEF correlated with ratings on satiation, nausea, uncomfortable abdominal swelling, body image, and fear of being fat (for all, P < 0.01).

Conclusion: In AN women, blindly infused loads induced a dose-dependent increase in TEF, which correlated with the increase in plasma cortisol, ACTH, and catecholamines as in unpleasant sensations, fear of being fat, and anxiety as well as a decline in elevated basal ß-endorphin. These results could explain the difficulty for AN patients in gaining weight.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
ANOREXIA NERVOSA (AN) is a disorder leading to chronic malnutrition. Renutrition is part of the treatment (1). However, body weight gain is a long-lasting process difficult to obtain in AN patients. In fact, many authors have shown that the additional energy-intake required to gain body weight is raised in AN (2, 3, 4, 5), and that energy supply usually recommended to treat patients is higher than in other diseases (1, 4, 5).

To explain the high energy need during refeeding, some authors have suggested that AN patients, who are afraid of overweight and obesity, lie to the dietitian, throw their food away, and/or vomit (2). This is supported by studies showing discrepancies between the low resting energy expenditure (REE) in AN patients during the fasting phase and the high energy needs during refeeding (3, 6, 7). Other authors have suggested that REE, which is low before renutrition, may increase during refeeding (6, 7). This could be a key factor explaining elevated energy needs in AN patients during renutrition. In this context, we found that thermic effect of food (TEF) was elevated during the refeeding period in malnourished AN patients (8). This elevated TEF could be due to hormonal modifications observed by others in AN patients: an increase in plasma cortisol (9), ACTH (9), and epinephrine or a high tonic sympathetic support (10, 11, 12).

The relative influence of psychological, behavioral, and somatic factors on the elevated TEF in malnourished AN patients who submitted to refeeding has not yet been studied. It is also not clear to what extent they stem from the hormonal changes observed in AN patients after an energy load. This provided us with the opportunity to study the relationships between psychological or somatic factors and hormonal changes before and after nasogastric infusion of two caloric loads and one noncaloric load in a double-blind setting in 15 AN women and in 15 healthy women.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

Fifteen malnourished AN women were studied after hospital admission to the Endocrinology and Nutrition Unit of the University Hospital of Dijon (Dijon, France). Their mean body mass index (BMI) was 13.6 ± 1.2 kg·m–2 (range, 10.7–15.9) and their mean age was 23 ± 4 yr (range, 18–29). All patients were hospitalized for renutrition because of their severe malnutrition and had accepted a nasogastric tube to infuse caloric mixtures to supplement their oral energy intake. Diagnosis of AN was assessed according to the criteria of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (1). All patients had the restrictive form of the disease and amenorrhea. Exclusion criteria were: bulimia or vomiting, age less than 16 yr, use of serotoninergic drugs or any drug susceptible to increase energy expenditure (EE) or to alter mood, and gain of more than 1 kg during the previous 4 wk.

Fifteen healthy women with normal eating behavior served as controls. Their mean BMI was 21.6 ± 1.9 kg·m–2 (range, 19.2–24.3) and their mean age was 24 ± 3 yr (range, 19–31). They were matched for age and sex with the AN patients. They had no medical history, no eating disorder, and took no medication. All healthy subjects were recruited from the students of the Medicine Faculty. The present study was approved by an ethics committee (Paris, France). All subjects gave written informed consent to participate in this prospective study.

General procedure and temporal pattern

All subjects participated in three experimental situations differing in the content of the loads and performed in random order: a nonenergetic (colored water), a 300-kcal, and a 700-kcal load (Sondalis; Nestlé Nutrition, Vevey, Switzerland). All injected gastric loads were of same volume (466 ml) and of similar color. The energy densities for the 300- and 700-kcal loads were 0.64 and 1.5 kcal/ml, respectively. The loads were infused before the beginning of the renutrition program. It was done through an opaque nasogastric tube from a pouch hidden from the subject and prepared without knowledge of the physician (double-blind design). The three experimental situations (0, 300, and 700 kcal) took place during the same week (separated from each other by a free interval of 1 d) in a random order. In AN patients, the three experimental sessions were carried out before the renutrition program by tube feeding. In AN patients, the mixtures were infused by the nasogastric tube in a double-blind design to avoid bias related to fear from knowledge of the energy load. It was explained to the patients before sessions that the drip provided "a nutritive mixture whose digestive assimilation and side effects were being investigated." Calorie content of the mixtures was not mentioned. Gastric infusion was chosen to avoid incomplete meal ingestion. The energy content of the loads (300 and 700 kcal) was selected as a function of the usual energy intake in AN restrictive patients; in our cohort of 487 patients hospitalized for AN and malnutrition, the mean energy intake was 860 ± 45 kcal per 24 h at admission, with a lunch of 294 ± 27 kcal.

In each experimental situation, the schedule was as follows. Subjects were asked to fast for 12 h. At 0800 h, a small indwelling heparinized catheter was inserted into the cephalic vein of the forearm for blood sampling and a nasogastric tube was placed in healthy subjects. In AN patients, the nasogastric tube was left permanently for further enteral nutrition. After a 20-min rest period for habituation to the ventilated-hood system, oxygen consumption and carbon dioxide production were recorded for 30 min (from 0830–0900 h) to evaluate REE. At 0900 h (t0), a first 6-ml blood sample was drawn for basal hormonal determinations and the subject’s initial feelings were recorded. Then, one of the three liquid mixtures (0, 300, or 700 kcal) was administered during 40 min through the nasogastric tube. During infusion then during the following 240 min, VO2 and VCO2 were continuously measured to evaluate the TEF. A 6-ml blood sample was drawn again 90, 180, and 270 min after the beginning of load infusion (t90, t180, t270). The subject’s feelings were evaluated before and 60, 120, 180, 240, and 300 min after the beginning of the blindly infused load (at t60, t120, t180, t240, and t300). Energy intake, which was left ad libitum in each subject, was carefully recorded over the 3 previous days.

Measurements

Body composition. Fat mass and fat-free mass were evaluated from the mean of skinfold thickness and bioelectrical impedance. Skinfold thickness was measured in four sites (biceps, triceps, subscapular, and suprailiac areas) using a Harpenden caliper (6). Bioelectrical impedance measurements were made using a two-frequency analyzer (50 kHz and 1 MHz; IMP BO 1; Impulse, Caen, France) previously validated (13).

Energy expenditure. Oxygen consumption and carbon dioxide production were measured with an open-circuit ventilated-hood system (14, 15). Gas concentrations were evaluated using a differential paramagnetic analyzer for oxygen (Klogor, Lannion, France) and an infrared analyzer for carbon dioxide (Hartmann and Braun Instruments, Frankfurt, Germany). Gas flow (50 ± 5 liters·min–1) was controlled by a mass-flow meter (Setaram, Lyon, France). Data were continuously recorded every 30 sec. The system was checked regularly by burning alcohol (the recovery was 97.4 ± 1.1% and 98.5 ± 0.9% for oxygen and carbon dioxide, respectively).

Subjective feelings. They were evaluated using visual analog scales of 100 mm, anchored with rating "not at all" at the left extremity and "very much" at the right (16). Questions concerned the following feelings: rating of satiation (how hungry do you feel now?), liking to eat (would you like to eat now?), nausea (do you feel nauseous?), uncomfortable abdominal swelling (do you experience stomach bloating?), abdominal pain (do you have a stomach ache?), gastric distension (do you experience dyspepsia, i.e. gastric fullness?), sleepiness (do you feel sleepy now?), depressive state, anxiety (do you feel depressed or anxious now?), fear of being fat (are you afraid you are becoming fat from this meal?), sensations concerning the loads (do you think that this infusion is nourishing, heavy to digest?), and caloric content of the loads (do you feel that this infusion is caloric?). Body image was also evaluated on a four-point scale (0, very thin; 1, rather thin; 2, normal; 3, fat) from four different women body images (computer-made drawing from photos of women with a BMI of 18, 20, 22, and 25 kg/m2); the subjects had to indicate one of the four drawings, after they have read the question "at this time, how do you feel?"

Hormonal determination. Blood samples were immediately centrifuged and serum stored at –70 C until assay. Plasma immunoreactive concentrations of insulin (insulin-CT; Cisbio International, Saclay, France), ß-endorphin (Cisbio International), and ACTH (ELSA-ACTH, Cisbio International) were determined by RIA. Cortisol, prolactin (Serono, Boulogne, France), dopamine, epinephrine, and norepinephrine (Eurogenetics, Tosoh, France) were evaluated by immunochemistry. All determinations were made within the same assay for each hormone. The normal ranges were the following (17): for ß-endorphin, 2–12 pmol/liter (intraassay variation, 5%); for fasting insulin, 3–10 mUI/liter (intraassay variation, 4%); for ACTH, 3–10 pg/ml (intraassay variation, 8%); for cortisol, 300–480 ng/ml (intraassay variation, 6%); for prolactin, 100–450 pg/ml (intraassay variation, 7%); for dopamine, 0.05–0.15 nmol/liter (intraassay variation, 6%); for epinephrine, 0.05–0.12 nmol/liter (intraassay variation, 8%); and for norepinephrine, 1.2–3.0 nmol/liter (intraassay variation, 8%).

Calculation and statistics

Values are expressed as mean ± SD. EE was calculated as indicated previously (17, 18). TEF was expressed as the integrated increase in EE above REE during the 5 h after the beginning of the gastric loads (8). Hormonal responses after loads were calculated as the mean change observed at t90, t180, and t270 with respect to basal values and as integrated output over 5 h (area under the curve). Subjective feelings were evaluated as the mean change measured at t60, t120, t180, t240, and t300 with respect to basal values. Differences between experimental situations (0, 300, and 700 kcal) and subjects (AN patients and controls) were analyzed using a variance analysis (ANOVA) for parametric values and by the Kruskal-Wallis or the Friedman repeated measures test for the nonparametric ones. Student-Newman Keuls’ post hoc test was then used to investigate within-subject variations. Student t test or a Mann-Whitney U test was used to compare groups (AN and healthy women). Correlations between variables were done using Pearson’s test. All statistical analyses were conducted on Systat software (Systat Software Inc., Richmond, CA) with a statistical threshold fixed at P < 0.05.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
As shown in Table 1Go, mean spontaneous caloric intake and REE were lower in AN patients than in the healthy women (P < 0.05).


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  		TABLE 1. Body weight, body composition, caloric intake, and REE in the 15 healthy women and in the 15 AN patients

 
AN patients: TEF

In AN patients, EE increased even after the 0-kcal load (+49 ± 19 kcal, P < 0.05; Fig. 1Go). This increase was observed in 12 of the 15 patients. For the 300- and 700-kcal loads, TEF represented 44 and 33% of the load, respectively (compared with 16% in controls).


Figure 1
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  		FIG. 1. TEF in response to the three blindly infused gastric loads (0, 300, and 700 kcal) in the 15 AN patients and in the 15 healthy women. Values (means ± SD) represent TEF during the 240 min after the end of gastric load. No TEF after the 0-kcal load in controls. Significant TEF with 0-kcal load in AN patients (P < 0.01). For all loads, TEF was higher in AN patients than in control subjects (P < 0.01). *, P < 0.02 in each group between 0- and 300-kcal and between 300- and 700-kcal loads. *, P < 0.001 in each group between the 0- and 700-kcal loads.

 
AN patients: subjective feelings

Food sensations. In AN patients, rating of satiation increased significantly after the three gastric loads (Fig. 2Go). A satiating effect was reported even after the 0-kcal load at t60 (P < 0.05). The satiation rating was 1.4 times higher after the 700-kcal load than after the 300-kcal load (P < 0.05), itself being 6.4 times the 0-kcal load (P < 0.05). The liking to eat rating decreased after the three loads (data not shown; P < 0.01). This was noted even for the 0-kcal load at t60 (P < 0.05). This decrease in liking to eat rating correlated with the increase in rating of satiation (r = 0.754; P < 0.01). Rating of the calorie content of the loads correlated with its actual energy content (r = 0.637; P < 0.01).


Figure 2
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  		FIG. 2. Satiation rating after loads in the 15 AN patients and in the 15 healthy women. Top, Mean ± SE. **, P < 0.02 between AN patients and healthy women for 300- and 700-kcal loads. P < 0.01 between loads (0 and 300, 300 and 700) in both groups. Bottom, From visual analogic scales (0–100 mm) before and after loads: squares, 700-kcal load; triangles, 300 kcal; circles, 0 kcal. On the left, the 15 AN patients and on the right the 15 healthy women. All AN values, including the preload ones (0), were higher than those in healthy women (P < 0.01). In both groups, the 700-kcal values were higher than the 300-kcal ones, themselves higher than the no-calorie ones (P < 0.05). *, P < 0.05; **, P < 0.02; and ***, P < 0.01 vs. preload value.

 
Digestive feelings. Rating of nausea increased significantly after the three gastric loads, including the 0-kcal one (Fig. 3Go). Nausea was 1.2 times higher after 700-kcal load than after 300-kcal load (not significant). The latter was two times higher than after the 0-kcal load (P < 0.05). For other sensations (gastric distention, uncomfortable abdominal swelling, pain), the 700-kcal load induced a higher level of rating than did the 300-kcal one (P < 0.05), itself inducing more sensations than the 0-kcal load did (data not shown; P < 0.05).


Figure 3
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  		FIG. 3. Nausea rating after loads in the 15 AN patients and in the 15 healthy women. Estimated from visual analogic scales (0–100 mm). Nausea rating increased in AN patients according to the load (P < 0.01), but not in controls. Changes were significant (vs. fasting) for any load: *, P < 0.05 for 0-kcal and **, P < 0.001 for 300- and 700-kcal loads.

 
Mood. Sleepiness, anxiety, and depressive state ratings increased after each load (P < 0.05 vs. preload), but did not differ between 300- and 700-kcal loads. After the 700-kcal load, a shift in body image rating from "rather thin" to "fat" (P < 0.01) and in "fear of being fat" from "moderate" to "high" were noted (Fig. 4Go; P < 0.05).


Figure 4
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  		FIG. 4. Fear of being fat in the 15 AN patients and in the 15 healthy women, in response to the blindly infused gastric loads. Fear of being fat on the 0–100 visual analog scale. Time, After the beginning of the load. AN, squares; C, healthy women (circles). 0, 300, and 700: No calorie, 300-kcal load, 700-kcal load. 700- and 300-kcal curves, Significantly higher in AN patients than in healthy women (P < 0.01). For no-calorie load, the point at 1 h was significantly higher in AN patients than in controls (P < 0.05). In AN patients, any point of the 700-kcal curve was higher than the corresponding 300- and 0-kcal points (P < 0.01). The 2- and 3-h points from the 300-kcal curve were higher than those from the 0-kcal curve (P < 0.05).

 
Relationships between sensations. The energy content of the loads correlated positively (P < 0.01 for all) with TEF (r = 0.807) and with rating of satiation (r = 0.821), liking to eat (r = –0.513), nausea (r = 0.608), uncomfortable abdominal swelling (r = 0.479), body image from "thin" to "fat" (r = 0.545) and rating for fear of being fat (r = 0.735) and anxiety (r = 0.621). Higher the load was higher its satiating effect and digestive complaints (P < 0.01). TEF correlated with ratings of satiation (r = 0.655), nausea (r = 0.670), liking to eat (r = –0.393), uncomfortable abdominal swelling (r = 0.464), "body image" from thin to fat (r = 0.506) and fear of being fat (r = 0.607; for all, P < 0.01).

AN patients: hormonal levels

Mean basal plasma ß-endorphin level in AN patients was six times the upper limit of the normal range (Fig. 5Go; P < 0.001). No change was observed after the 0-kcal load, when a decrease in ß-endorphin was noted at t90 after the 300-kcal load and at t90, t180, t270 after the 700-kcal load (P < 0.05). This decrease in ß-endorphin correlated with TEF (r = 0.495; P < 0.05) and load (r = 0.427; P < 0.05).


Figure 5
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  		FIG. 5. Plasma ß-endorphin response to the three loads in the 15 AN patients and in the 15 healthy women. AN, AN patients; C, controls (healthy women). The upper limit of normal was 11 pmol/liter. 0, 300, and 700: 0-, 300-, and 700-kcal loads. *, P < 0.05 vs. before load; **, P < 0.01 vs. 300 kcal and value before load in AN patients. In healthy women, the 700-kcal load was followed by a significant increase in plasma ß-endorphin at t180 (vs. basal value; P < 0.05). All control values were significantly lower than any of the values in AN patients (P < 0.001).

 
Mean plasma ACTH increased significantly after the 300- (P < 0.05) and the 700-kcal loads (P < 0.01; Table 2Go). Significant increases were observed for plasma cortisol, norepinephrine, and dopamine after the 700-kcal load (Table 2Go; P < 0.05). There were smaller increases in hormone levels after the 300-kcal load: area under the curve was above zero in eight of the 15 AN patients for epinephrine, in nine patients for norepinephrine, in 10 patients for dopamine, and in 11 of the 15 patients for cortisol (P < 0.05 using Wilcoxon test). The increase in ACTH and norepinephrine levels was correlated with TEF values (r = 0.372 and 0.408, respectively; P < 0.05). In contrast, there was no change in epinephrine nor in prolactin level after any load. Serum glucose and plasma insulin increased after the three loads (P < 0.01), with values higher after the 700-kcal load than after the 300-kcal load (Table 3Go for insulin; P < 0.01).


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  		TABLE 2. Plasma ACTH, cortisol, epinephrine, norepinephrine, and dopamine in response to the three blindly infused gastric loads (0, 300, and 700 kcal) in the 15 AN patients

 

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  		TABLE 3. Plasma insulin level in response to 0, 300-, and 700-kcal loads in the 15 AN patients and in the 15 healthy women

 
Significant correlations were noted between the hormonal changes and variation in ratings. For example, the decrease in ß-endorphin correlated with the increase in satiation rating (r = –0.388, P < 0.05), uncomfortable abdominal swelling (r = –0.418, P < 0.01), and body image from "thin" to "fat" (r = –0.426, P < 0.01). ACTH increase correlated with the increase in rating of satiation (r = 0.532, P < 0.01), nausea (r = 0.393, P < 0.05), and uncomfortable abdominal swelling (r = 0.550, P < 0.01). Insulin increase correlated with increase in satiation (r = 0.432, P < 0.01) and decrease in liking to eat (r = 0.376; P < 0.05).

Healthy women: TEF

There was no change in EE after the 0-kcal load. After the 300- and 700-kcal loads, EE increased (Fig. 1Go; P < 0.05). It represented 14 and 16% of the 300- and 700-kcal loads, respectively. This EE increase was less important than in AN patients (P < 0.01; Fig. 1Go).

Healthy women: subjective feelings

Food sensations. Rating of satiation was reported only after the 300 and the 700-kcal loads (P < 0.05 vs. preload value). Liking to eat increased after the 0-kcal load (P < 0.05) but decreased after the 300-kcal load (P < 0.05) and even more after the 700-kcal load (P < 0.02).

Digestive feelings. Rating for nausea, uncomfortable abdominal swelling, abdominal pain, and gastric distension were near from zero value. They only increased slightly after the 700-kcal load (P < 0.05).

Mood. Anxiety and depressive states as well as fear of being fat were near from zero and did not change significantly after any load (Fig. 4Go).

Healthy women: hormonal levels

There was no change in plasma level of cortisol, ACTH, dopamine, epinephrine, or norepinephrine levels after the three loads. Plasma ß-endorphin increased slightly only after the 700-kcal load (P < 0.05). As expected, the postload increase in serum glucose and insulin level correlated with the level of the load (r = 0.612) and TEF (r = 0.495; P < 0.01). The insulin increase was positively correlated with rating of satiation and negatively with liking to eat (r = 0.324 and 0.412; P < 0.01).

AN patients vs. healthy women

Irrespective of the load (0, 300, and 700 kcal), TEF was higher in AN patients than in healthy women (P < 0.001). For each load, rating of satiation was always higher (P < 0.01) and liking to eat always lower in AN patients than in healthy women (P < 0.01; Fig. 2Go). Similarly, rating of abdominal discomfort, nausea, and pain were always higher in AN patients (P < 0.01 for all). Postload ß-endorphin was always lower in healthy women than in AN patients (P < 0.01). Plasma cortisol, ACTH, dopamine, epinephrine, and norepinephrine area under the curves were always lower in healthy women than in AN patients (P < 0.05). Serum glucose did not differ between groups. Insulin response to the 700-kcal load was higher in the AN patients than in the healthy women (P < 0.05), but not concerning the 0- and the 300-kcal loads.


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
The present study showed that blindly infused gastric loads of three different energy content induced higher dose-dependant increases in TEF and in ratings of satiation, abdominal feelings, and mood changes in AN patients than in control healthy women. The energy loads induced a dose-dependent decrease in ß-endorphin and a dose-dependent increase in ACTH, cortisol, norepinephrine, and dopamine levels in AN patients, whereas there was almost no change in these variables in the healthy women.

In AN patients, TEF was higher than that observed in healthy women. It correlated with the energy input, as shown previously (6, 8). In AN patients, actually TEF represented more than 30% of the loads, compared with 14–16% in controls. It seems that this high TEF could be related to the anxiety level, due to fear of being fat and setting obese (2, 3, 7). Our findings that the changes in body image and in fear of eating correlated with the energy content of the load and TEF are consistent with this idea.

Satiation and the decrease in liking to eat ratings were linked with the energy content of the load in both controls and the AN patients. Because the loads were blindly administered and had similar osmolarity and volume, energy input would seem to be the major factor of wanting and liking to eat in our subjects, in a study using liquid loads without any passing through the mouth. Our results contrast with those of Rolls and Roe (18), who studied 25 lean (BMI, 20–26 kg/m2) and 29 obese women (BMI > 28 kg/m2). These authors administered blindly via a nasogastric tube, as in our study, a preload, but the load varied 2-fold in volume and/or in energy (so in energy density); the subjects were then requested to eat freely from a variety of foods. The authors showed no difference between the three loads (200 ml/200 kcal, 400 ml/200 kcal, 400 ml/400 kcal) in decreasing hunger ratings and increasing fullness ratings. This discrepancy with our results could be explained by the difference in energy input: indeed, in our study, the clearest results in healthy women were observed with a load near to the one of a normal lunch (700 kcal). Interestingly, these authors showed that wanting to eat (i.e. prospective consumption of food from hunger feeling) was affected (i.e. decreased) only with the 400-ml loads. In men, Shilde et al. (19) and Cecil et al. (20) have shown that normal-weight subjects were less hungry and reduced their food intake after blind loads from fat or carbohydrate.

Interestingly, the level of nausea, bloating, and abdominal pain was load-dependent, despite similar infused volume. This suggests that AN patients perceived the level of energy load at the gastric or intestinal level. But whether this was related to difference in energy output through the pylorus could not be determined (18). The fear of being fat was a likely source of these alterations in feelings, because anxiety rating, abdominal discomfort rating, and the worsening in body image increased with the load. It is of note that these changes correlated with the energy content of the load and occurred despite low or relatively low inputs (700 and 300 kcal).

These changes in feelings were associated with alterations in hormone levels. First, there was a dose-dependent decrease in ß-endorphin level. In this context, food intake has been shown by others to modify plasma ß-endorphin-like immunoreactivity in humans (21, 22, 23). Our group and others have described elevated resting ß-endorphin level in AN patients (24, 25). In the present study, we observed that ß-endorphin was 7-fold higher in AN patients than in healthy women, as noted in a previous study (24). In this study, we observed a dose-dependent decline in ß-endorphin level in AN patients. This decrease could partly explain the abdominal discomfort, anxiety, and depressive states after a meal. This may also be the reason why some AN patients feel a need to take physical exercise after a meal, because exercise stimulates release of ß-endorphin (25). This decrease in ß-endorphin could explain, at least in part, the difficulties of eating among such patients. Indeed, with this drop, they lose the "sensory profit related to the elevated fasting ß-endorphin level" (26). However, our observations could not evidence ß-endorphin resistance in AN, nor indicate whether the decrease in plasma reflects a similar decrease in the brain. In the present study, anxiety correlated with energy load and was associated with dose-dependent increases in plasma ACTH, cortisol, dopamine, epinephrine, and norepinephrine levels. These hormonal changes could be responsible for an increase in EE (10, 11, 12). The increase in dopamine points to a meal-dependent stress, which was supported by the increase in anxiety and fear (27, 28). These hormonal changes could be responsible for the TEF increase (11, 12). Indeed, some authors have shown that central as well as peripheral norepinephrine regulation are disturbed in AN patients (29, 30, 31, 32, 33), during fasting (32), after stimulation (34), and also in response to the meal (35). Kaye et al. (36, 37) also described differences in catecholamine metabolism at different stages of the disease. Such modifications could modify the mood of the patients (38). Meal-induced stress is consistent also with the dose-dependent increase in cortisol level after the loads. We did not observe any change in prolactin levels in these malnourished AN patients who had low energy intake at the time of the sessions. Nadal et al. (39) described an increase in plasma prolactin after a 3-d deprivation in the horse. In contrast, other authors found a blunted prolactin response in AN patients after stimulation by L-tryptophan (40) or D-fenfluramine (41). Goettler et al. (42) showed a decrease in prolactin release after meal in cancer anorectic patients.

Conclusion

The present study suggests that, even before refeeding, TEF is high in AN patients. This could be related to the fear of gaining weight and becoming obese. The loads, by virtue of their energy content, may trigger release of ACTH, cortisol, dopamine, and catecholamines, which contribute to an increase in TEF and to changes in feelings such as hunger or abdominal bloating. The decrease in ß-endorphin could contribute to the load-dependent anxiety and depressive states and thus to the fear of eating during meals. Because this elevated TEF expends at least one third of the energy of the meals, it is not surprising that these AN malnourished patients have difficulties in gaining weight. Further studies are needed to determine the dependence of this TEF increase on the nutrient content of the meals (relation with protein and/or carbohydrate content) and whether TEF will be normalized by reaching normal BMI and by recovery of AN.


   Footnotes
 
Disclosure Statement: The authors have nothing to declare.

First Published Online March 6, 2007

Abbreviations: AN, Anorexia nervosa; BMI, body mass index; EE, energy expenditure; REE, resting EE; TEF, thermic effect of food.

Received June 20, 2006.

Accepted February 23, 2007.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Rigaud D 2003 Anorexie, boulimie, compulsions. Les troubles du comportement alimentaire. Paris: Marabout; 274–296
  2. Graham GG 1981 Weight gain in anorexia nervosa. Am J Clin Nutr 34:599–600[Medline]
  3. Stordy BJ, Marks V, Kalucy RS, Crisp AH 1977 Weight gain, thermic effect of glucose and resting metabolic rate during recovery from anorexia nervosa. Am J Clin Nutr 30:138–146[Abstract/Free Full Text]
  4. Walker J, Roberts SL, Halmi KA, Goldberg SC 1979 Caloric requirements for weight gain in anorexia nervosa. Am J Clin Nutr 32:1396–1400[Abstract/Free Full Text]
  5. Forbes GB, Kreipe RE, Lipinski B 1982 Body composition and the energy cost of weight gain. Hum Nutr Clin Nutr 36:485–487[Medline]
  6. Melchior JC, Rigaud D, Rozen R, Malon D, Apfelbaum M 1989 Energy expenditure economy induced by decrease in lean body mass in anorexia nervosa. Eur J Clin Nutr 43:793–799[Medline]
  7. Obarzanek E, Lesem MD, Jimerson DC 1994 Resting metabolic rate of anorexia nervosa patients during weight gain. Am J Clin Nutr 60:666–675[Abstract/Free Full Text]
  8. Moukaddem M, Boulier A, Apfelbaum M, Rigaud D 1997 Increase in diet-induced thermogenesis at the start of refeeding in severely malnourished anorexia nervosa patients. Am J Clin Nutr 66:133–140[Abstract/Free Full Text]
  9. Casper RC 1996 Carbohydrate metabolism and its regulatory hormones in anorexia nervosa. Psychiatry Res 62:85–96[CrossRef][Medline]
  10. Bell C, Seals DR, Monroe MB, Day DS, Shapiro LF, Johnson DG, Jones PP 2001 Tonic sympathetic support of metabolic rate is attenuated with age, sedentary lifestyle and female sex in healthy adults. J Clin Endocrinol Metab 86:4440–4444[Abstract/Free Full Text]
  11. Monroe MB, Seals DR, Shapiro LF, Bell C, Johnson DG, Parker Jones PP 2001 Direct evidence for tonic sympathetic support of resting metabolic rate in healthy adult humans. Am J Physiol Endocrinol Metab 280:E740–E744
  12. Menozzi R, Bondi M, Baldini A, Venneri MG, Velardo A, Del Rio G 2000 Resting metabolic rate, fat-free mass and catecholamine excretion during weight loss in female obese patients. Br J Nutr 84:515–520[Medline]
  13. Rigaud D, Cohen B, Melchior JC, Moukaddem M, Reveillard V, Apfelbaum M 1997 Refeeding improves muscle performances without normalization of muscle mass and oxygen consumption in anorexia nervosa. Am J Clin Nutr 65:1845–1851.[Abstract/Free Full Text]
  14. Van Wymelbeke V, Brondel L, Brun JM, Rigaud D 2004 Factors linked to the increase in resting energy expenditure during refeeding in malnourished anorexia nervosa patients. Am J Clin Nutr 80:1469–1477[Abstract/Free Full Text]
  15. Rigaud D, Hassid J, Meulemans A, Poupard AT, Boulier B 2000 A paradoxical increase in resting energy expenditure at the limit of life in starved patients. Am J Clin Nutr 72:355–362[Abstract/Free Full Text]
  16. Rigaud D, Trostler N, Rozen R, Vallot T, Apfelbaum M 1995 Gastric distention, hunger feeling and energy intake after balloon implantation in severe obesity: a 4 months-double blind placebo controlled study. Int J Obesity 19:489–495[Medline]
  17. Colas-Linhart N, Perdrisot R, Petiet A, Bok B 1986 Un dosage radioimmunologique de béta-endorphine: études de spécificité. J Biophys Biomécan 10:131–134
  18. Rolls BJ, Roe LS 2002 Effect of the volume of liquid food infused intragastrically on satiety in women. Physiol Behav 76:623–631[CrossRef][Medline]
  19. Shilde DJ, Caballero B, Reidelberger R, Rolls BJ 1995 Accurate energy compensation for intragastric and oral nutrients in lean males. Am J Clin Nutr 61:754–764[Abstract/Free Full Text]
  20. Cecil JE, Castiglione K, French S, Francis J, Read NW 1998 Effects of intragastric infusions of fat and carbohydrate on appetite ratings and food intake from a test meal. Appetite 30:65–77[CrossRef][Medline]
  21. Melchior JC, Rigaud D, Chayvialle JA, Colas-Linhart N, Petiet A, Comoy E, Apfelbaum M 1994 The palatability of a meal influences the release of ß endorphin and some potential regulators of food intake in healthy subjects. Appetite 22:233–244[CrossRef][Medline]
  22. Melchior JC, Rigaud D, Colas-Linhart N, Petiet A, Girard A, Apfelbaum M 1991 Immunoreactive ß-endorphin increases after aspartam chocolate drink in healthy human subjects. Physiol Behav 50:941–944[CrossRef][Medline]
  23. Zelissen PM, Koppeschaar HP, Thijssen JH, Erkelens DW 1991 ß Endorphin and insulin responses to different meals in obesity. Horm Res 36:32B–35B
  24. Melchior JC, Rigaud D, Colas-Linhart N, Rozen R, Fantino M, Apfelbaum M 1990 Negative allesthesia and decreased endogenous opiate system activity in anorexia nervosa. Pharmacol Biochem Behav 35:885–888[CrossRef][Medline]
  25. Heitkampf HC, Huber W, Scheib K 1996 ß Endorphin and adrenocorticotrophin after incremental exercise and marathon running-female responses. Eur J Appl Physiol Occup Physiol 72:417–424[CrossRef][Medline]
  26. Russell J, Bauer LA, Beaumont PJ, Byrnes S, Gross G, Touyz S, Abraham S, Zipfel S 2001 Altered energy metabolism in anorexia nervosa. Psychoneuroendocrinol 26:51–63[CrossRef][Medline]
  27. Koob GF 1999 Corticotropin-releasing factor, norepinephrine and stress. Biol Psychiatry 46:1167–1180[CrossRef][Medline]
  28. Murakami K, Akana SF, Dallman MF 1997 Dopamine-ß-hydroxylase activity is necessary for hypothalamo-pituitary-adrenal (HPA) responses to ether, and stress-induced facilitation of subsequent HPA responses to acute ether emerges as HPA responses are inhibited by increasing corticosterone. J Neuroendocrinol 9:601–608[CrossRef][Medline]
  29. Nedvidkova J, Dostalova I, Bartak V, Papezov H, Pacak K 2004 Increased subcutaneous abdominal tissue norepinephrine levels in patients with anorexia nervosa: an in vivo microdialysis study. Physiol Res 53:409–413[Medline]
  30. Bartak V, Vybiral S, Papezova H, Dostalova I, Pacak K, Nedvidkova J 2004 Basal and exercise-induced sympathetic nervous activity and lipolysis in adipose tissue of patients with anorexia nervosa. Eur J Clin Invest 34:371–377[CrossRef][Medline]
  31. Pirke KM 1996 Central and peripheral norepinephrin regulation in eating disorders. Psychiatry Res 62:43–49[CrossRef][Medline]
  32. Kaye WH, George DT, Gwirtsman HE, Jimerson DC, Goldstein DS, Ebert MH, Lake CR 1990 Isoproterenol infusion test in anorexia nervosa: assessment of pre- and post-ß-noradrenergic receptor activity. Psychopharmacol Bull 26:355–359[Medline]
  33. Lesem MD, George DT, Kaye WH, Goldstein DS, Jimerson DC 1989 State-related changes in norepinephrine regulation in anorexia nervosa. Biol Psychiatry 25:509–512[CrossRef][Medline]
  34. Nakagawa K, Matsubara M, Obara T, Kubo M, Akikawa K 1985 Responses of pituitary and adrenal medulla to insulin-induced hypoglycemia in patients with anorexia nervosa. Endocrinol Jpn 32:719–724[Medline]
  35. Pirke KM, Kellner M, Philipp E, Laessle R, Krieg JC, Fichter MM 1992 Plasma norepinephrine after a standardized test meal in acute and remitted patients with anorexia nervosa and in healthy controls. Biol Psychiatry 31:1074–1077[CrossRef][Medline]
  36. Kaye WH, Jimerson DC, Lake CR, Ebert MH 1985 Altered norepinephrine metabolism following long-term weight recovery in patients with anorexia nervosa. Psychiatry Res 14:333–342[CrossRef][Medline]
  37. Kaye WH, Gwirtsman HE, Lake CR, Siever LJ, Jimerson DC, Ebert MH, Murphy DL 1985 Disturbances of norepinephrine metabolism and {alpha}-2 adrenergic receptor activity in anorexia nervosa: relationship to nutritional state. Psychopharmacol Bull 21:419–423[Medline]
  38. Laessle RG, Schweiger U, Pirke KM 1988 Mood and orthostatic norepinephrine response in anorexia nervosa. Psychiatry Res 24:87–94[CrossRef][Medline]
  39. Nadal MR, Thompson DL, Kincald LA 1997 Effet of feeding and feed deprivation on plasma prolactin, insulin, growth hormone and metabolites in horse. J Anim Sci 75:736–744[Abstract/Free Full Text]
  40. Brewerton TD, Jimerson DC 1996 Studies of serotonin function in anorexia nervosa. Psychiatry Res 62:31–42[CrossRef][Medline]
  41. Monteleone P, Brambilla F, Bortolotti F, Maj M 2000 Serotonergic dysfuncion in eating disorder: relationship to eating behavior, nutritional status and general psychopathology. Psychol Med 30:1099–1110[CrossRef][Medline]
  42. Goettler DM, Levin L, Chey WY 1990 Postprnadial level of prolactin and gut hormones in brast cancer patients. J Natl Cancer Inst 82:22–29[Abstract/Free Full Text]




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