AJP - Endo Journal of Applied Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab 292: E132-E137, 2007. First published August 15, 2006; doi:10.1152/ajpendo.00241.2006
0193-1849/07 $8.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
292/1/E132    most recent
00241.2006v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (3)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bossu, C.
Right arrow Articles by Estour, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bossu, C.
Right arrow Articles by Estour, B.

Energy expenditure adjusted for body composition differentiates constitutional thinness from both normal subjects and anorexia nervosa

Cécile Bossu,1 Bogdan Galusca,1,5 Sylvie Normand,6 Natacha Germain,1 Philippe Collet,2 Delphine Frere,3 François Lang,4 Martine Laville,6 and Bruno Estour1

Departments of 1Endocrinology, 2Rheumatology, 3Nuclear Medicine, and 4Psychiatry, Centre Hospitalier Universitaire, Saint-Etienne, France; 5Department of Endocrinology, University of Medicine and Pharmacy, "Gr.T.Popa," Romania; and 6Centre de Recherche en Nutrition Humaine de Lyon, France

Submitted 22 May 2006 ; accepted in final form 8 August 2006


   ABSTRACT
TOP
 ABSTRACT
SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Constitutional thinness (CT) is characterized by a low and stable body mass index (BMI) without any hormonal abnormality. To understand the weight steadiness, energetic metabolism was evaluated. Seven CT, seven controls, and six anorexia nervosa (AN) young women were compared. CT and AN had a BMI <16.5 kg/m2. Four criteria were evaluated: 1) energy balance including diet record, resting metabolic rate (RMR) (indirect calorimetry), total energy expenditure (TEE) (doubly labeled water), physical activity; 2) body composition (dual-energy X-ray absorptiometry); 3) biological markers (leptin, IGF-I, free T3); 4) psychological profile of eating behavior. The normality of free T3 (3.7 ± 0.5 pmol/l), IGF-I (225 ± 93 ng/ml), and leptin (8.3 ± 3.4 ng/ml) confirmed the absence of undernutrition in CT. Their psychological profiles revealed a weight gain desire. TEE (kJ/day) in CT (8,382 ± 988) was not found significantly different from that of controls (8,793 ± 845) and AN (8,001 ± 2,152). CT food intake (7,565 ± 908 kJ/day) was found similar to that of controls (7,961 ± 1,452 kJ/day) and higher than in AN (4,894 ± 703 kJ/day), thus explaining the energy metabolism balance. Fat-free mass (FFM) (kg) was similar in CT and AN (32.5 ± 2.9 vs. 34.1 ± 1.9) and higher in controls (37.8 ± 1.6). While RMR absolute values (kJ/day) were lower in CT (4,839 ± 473) than in controls (5,576 ± 209), RMR values adjusted for FFM were the highest in CT. TEE-to-FFM ratio was also higher in CT than in controls. Energetic metabolism balance maintains a stable low weight in CT. An increased energy expenditure-to-FFM ratio differentiates CT from controls and could account for the resistance to weight gain observed in CT.

energy metabolism balance; doubly labeled water

CONSTITUTIONAL THINNESS (CT), or leanness, was identified over the last decades as a nonpathological state of underweight that does not meet the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV criteria of anorexia nervosa (AN) (4). Contrary to the later pathology, the nonpathological state of CT in adult women is supported by the presence of menstruations (43), normal thyroid (32) and cardiac functions (36), and normal insulin sensitivity (47). Moreover, CT individuals are characterized by a body weight that has always been in the lower percentiles for age, gender, and ethnicity (2, 7). Familiality and heritability of thinness were also described (23, 28, 33) or demonstrated (7).

In a previous study (48), we evaluated CT women with low body mass indexes (BMIs) similar to those of AN (i.e., BMI <17.5 kg/m2). We found nutritional markers such as free T3 and IGF-I to be within normal ranges, whereas leptin levels were mildly decreased. Growth hormone (GH), ghrelin, and cortisol profiles also presented normal values, contrary to AN (48).

The mechanism behind low-weight steadiness in CT was not elucidated. Multifactorial etiology involves a combination of genetics in addition to yet unrecognized pathophysiological factors (7). Energy metabolism is considered a key target of genetic influences (31). Recently, gene determinations of thinness were postulated, some of them related to increased insulin sensitivity (12, 24) and others to regulation of feeding behavior and metabolic rate (13, 29). Conversely, it was shown that insulin sensitivity is normal in CT (47), and only some components of energy metabolism, like resting metabolic rate and postprandial thermogenesis, were evaluated (41, 49). Considering these incomplete data, we conducted a prospective study to evaluate the energy metabolism, including simultaneous assessment of food intake energy and total energy expenditure in very-low-weight CT subjects. We compared these data with those of normal BMI controls and with those of AN patients displaying similar very low body weight.


   SUBJECTS AND METHODS
TOP
 ABSTRACT
 SUBJECTS AND METHODS
RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
This study was reviewed and approved by the ethics committee on human research of Saint Etienne, France, and all subjects gave written, informed consent.

Subjects

Three groups of Caucasian female subjects were recruited for the study: seven CT, six AN, and seven controls. The studied CT and AN were matched by BMI.

The seven CT subjects were recruited at our outpatient clinic among the patients evaluated for leanness, using the following criteria: BMI between 14.5 and 16.5 kg/m2, stable throughout the postpubertal period, presence of physiological menstruations without estroprogestative treatment, and the desire for weight gain as the main reason for medical consultation.

All six AN subjects displayed active psychiatric disease according to the criteria of the DSM (1). Before onset of disease, the BMIs of the subjects ranged between 19.1 and 21.5 kg/m2. Thereafter, BMIs decreased to values <16.5 kg/m2, where they remained nearly stable during the last month before the study. Patients were recruited before starting any therapeutic approach. None of them used oral contraceptives, and all presented with secondary amenorrhea for at least 6 mo. Secondary amenorrhea occurred at least 12 mo after the first menses period. All patients had the restrictive form of AN. None of the subjects had a previous history of endocrine disease or psychiatric therapy at the moment of inclusion in the protocol.

The weight history from birth to 18 yr for each thin patient (including AN and CT) was retrospectively reconstituted using medical records and plotted against a reference set of BMI from the 3rd to 97th percentile (40). The family pedigree of weight was also recorded for three generations.

Seven controls (mean BMI 21.2 ± 1.1 kg/m2) were matched by age (18–26 yr) with AN and CT subjects.

In CT and controls, all data were collected during the follicular phase of cycle. None of the subjects included in this study was documented with a chronic or congenital disease or a form of addictive or abusive consumption (alcohol, smoking, drugs, or physical activity, etc.). None of them was taking any medication.

Psychological Profile

The food-related behavioral problems were evaluated by four psychiatric reference questionnaires in all three groups of subjects: the "silhouette" questionnaire of Jaeger et al. (22), the Dutch Eating Behavior Questionnaire validated by Van Strien et al. (51), the Eating Disorder Inventory (17), and the Eating Disorders Examination of Cooper and Fairburn (10). The psychological questionnaires measured complementary behavioral or psychiatric dimensions.

Body Composition Measurements

Dual-energy X-ray absorptiometry (DEXA) allowed for the quantification of the percentage of total body fat mass (FM) and fat-free mass (FFM) expressed in kilograms (LUNAR, DPX-L, <1% coefficient of variation) (16, 30).

Blood Samples

Fasting blood samples were immediately centrifuged, and plasma was stored at –80°C for each subject. Leptin was measured by radioimmunological technique (RIA Human Leptin kit, Linco Research). The manufacturer's reference range for a normal BMI (18–25 kg/m2) was 3.7–11.1 µg/l. The coefficient of interassay variation was 4.5%. Free T3 was measured by radioimmunological technique (Immunotech, Marseille, France). The manufacturer's reference range was 2.5–5.8 pmol/l. The coefficient of interassay variation was 4.9%. IGF-I was measured by immunoradiometric assay technique (Immunotech). The manufacturer's reference range was 219–644 ng/ml within the 20- to 30-yr-old age group. Interassay coefficient of variation was ≤6.8%.

Energy Metabolism Assessment

Energy intake. The assessment of dietary intake was realized over a period of 4 days, including 2 weekdays and a weekend. The subjects reported the four 24-h dietary records using an instruction manual for codification of foods, including photographs for estimations of portion size (3). Foods were presented in three sizes, including intermediate and extreme positions, permitting seven choices of the amount. Photographs of the portion sizes were previously validated for the SU.VI.MAX study (26). A nutritionist met with subjects to explain the collection of the data and then to ensure the accuracy of the collected data.

Food quotient (FQ) was calculated using Black's formula (5): FQ = [(710.71P) + (1,377.06F) + (746C)]/[(879.06P) + (1,948.34F) + (746C)], where P, F, and C are protein, fat, and carbohydrate intakes, respectively, expressed as grams per day.

Total energy expenditure. Total energy expenditure (TEE) was measured in ambulatory using doubly labeled water (DLW), a gold standard method (6, 44). The DLW technique uses a mixture of water labeled with two stable isotopes (2H218O, Eurisotop): deuterium (2H) and oxygen-18 (18O) (6, 45). After baseline urine samples were provided, a premixed dose of 0.05 g/kg 2H2O (99.9% 2H) and 1.05 g/kg H218O (10% 18O) was administered to the subjects. After dosing, two urine samples were collected at 3 and 4 h. Ten and fourteen days after dosing, the subjects returned to the laboratories, and urine samples were collected from two consecutive voids. Urine was stored at –20°C in cryogenically stable tubes until analysis by isotope ratio mass spectrometry. TEE was determined using the two-point method according to Schoeller et al. (44). The dilution spaces for 2H and 18O were calculated from the baseline and urine samples according to Coward et al. (38). The total body water (TBW) was calculated from the average of the dilution space of deuterium and oxygen-18, after correction for the isotopic exchanges, of 1.041 and 1.007, respectively. The production of CO2 was calculated according to the equation of Schoeller and al. (44)

Formula
with N being the average space of dilution of 2H and of 18O calculated by the method of the "plateau" using the isotopic enrichments of the 4-h postdose sample; ko and kd represent the hillsides of elimination calculated by linear regression of the logarithm of the isotopic enrichment according to time (days).

The following formula was used to calculate TEE:

Formula
Fasting respiratory quotient (RQ) was measured by indirect calorimetry.

Resting metabolic rate. Resting metabolic rate (RMR) was determined by use of the Deltatrac device for indirect calorimetry (Datex Instrumentarium, Helsinki, Finland) (15). Data were collected in the morning, after 12 h of fasting (alcohol and caffeine ingestion included) and physical activity restriction. A 1-h resting period preceded the assessment of RMR.

Energy expenditure related to physical activity. Physical activity was assessed with the MONICA Optional Study of Physical Activity Questionnaire (MOSPA-Q) (34), whose validity and reliability have been reported (39). MOSPA-Q quantified the average and daily energy expenditure over the last year, via professional, leisure, or sport activities.

Physical activity level (PAL = TEE/RMR) and activity energy expenditure (AEE = TEE – RMR) were also estimated.

To adjust energy expenditure for metabolic mass (FFM), RMR-to-FFM and TEE-to-FFM ratios were calculated as previously reported (25, 37).

Statistical Analysis

The results are presented as means ± SD. ANOVA was first used to perform a three-group analysis comparing constitutionally thin women with anorexic women and controls. When ANOVA was significant, we performed post hoc ANOVA tests (Fishers protected least significant difference and Tukey's-Kramer's test) for comparisons within all groups. Spearmann correlation index was calculated between leptin and FM in thin patients group (including CT and AN subjects) and between FFM and RMR in overall group. P < 0.05 was considered statistically significant (Statview 4.5 software).


   RESULTS
TOP
 ABSTRACT
 SUBJECTS AND METHODS
 RESULTS
DISCUSSION
 GRANTS
 REFERENCES
 
The psychological profile of CT women indicated that they wanted to gain weight. Typical psychological profile including food limitation, emotionality, and external excitement was evidence in AN patients but not in CT (data not shown).

In the CT group, the mean BMI was very low, approximately the 3rd percentile, throughout the growth period until the age of 18 (Fig. 1). Conversely, the mean BMI in AN subjects was normal (20.7 ± 1.0 kg/m2) before the onset of anorexic tendencies.


Figure 1
View larger version (14K):
[in this window]
[in a new window]

  		Fig. 1. Mean body mass index (BMI) growth curve of constitutionally thin (CT) subjects (n = 7). The BMI history from birth to 18 yr was reconstituted retrospectively (using medical records) for each thin patient; mean values were calculated and plotted against a reference set of BMI from 3rd to 97th percentile (40).

 
After excluding the index cases, we found an average of 2.5 thin subjects per family within the CT group. After a similar exclusion, the average of thin subjects in AN families was ~0.5 per family.

The results of energy balance in every group of study are shown in Table 1. The self-reported caloric intake for the CT subjects (7,565 ± 908 kJ/day) was similar to that of controls (7,961 ± 1,452 kJ/day) and significantly higher than that of the AN subjects (4,894 ± 703 kJ/day, P < 0.05). Similar percentages of nutrient consumed were found in CT and control groups. Compared with both controls and CT groups, the percentage of lipids consumed in AN patients was significantly lower. TEE measured by DLW (kJ/day) was similar in all three groups: 8,382 ± 988 in CT, 8,793 ± 845 in controls, and 8,001 ± 2,152 in AN. The mean calculated difference between energetic expenditure and caloric intake was similar in CT (816 kJ/day) and controls (832 kJ/day) and significantly higher in AN (3,161 kJ/day, P < 0.05) (Fig. 2).


View this table:
[in this window]
[in a new window]

  		Table 1. Energy balance of constitutional thinness, anorexia nervosa, and control subjects of the study

 

Figure 2
View larger version (28K):
[in this window]
[in a new window]

  		Fig. 2. Energy metabolism in CT, young women controls (C), and anorexia nervosa (AN). Shown are mean values of self-reported food intake energy, total energy expenditure (TEE), resting metabolic rate (RMR), and physical activity (PA).

 
By use of indirect calorimetry, the RMR of CT (4,839 ± 473 kJ/day) was found to be lower than in controls (5,576 ± 209 kJ/day) and higher than in AN (3,810 ± 937 kJ/day, P < 0.05). The CT energy expenditure due to physical activity, evaluated by MOSPA-Q (1,430 ± 284 kJ/day), was not significantly different from that of controls (2,051 ± 1,314 kJ/day) and AN subjects (1,511 ± 962 kJ/day). PAL and AEE of CT subjects were similar to those of controls, whereas in AN, they tend to be higher (Table 1).

The results of body composition measurements are shown in Table 2. The mean BMI (kg/m2) does not differ between the CT and AN groups (16.1 ± 0.6 vs. 15.8 ± 0.8, P = 0.35). The FFM (kg) was significantly lower in CT compared with controls (32.5 ± 2.9 vs. 37.8 ± 1.6, P = 0.026) and similar to that of AN (34.1 ± 1.9, P = 0.31). The FM (%) was significantly different among the three groups (CT, 18.3 ± 2.1; AN, 9.4 ± 5.4; controls, 26.2 ± 4.1; P < 0.05). RMR displayed a strong linear relationship with FFM (r = 0.522, P < 0.05) within the overall group (Fig. 3).


View this table:
[in this window]
[in a new window]

  		Table 2. Body composition and plasmatic nutritional markers of constitutional thinness, anorexia nervosa, and control subjects

 

Figure 3
View larger version (6K):
[in this window]
[in a new window]

  		Fig. 3. Relationships between body composition vs. RMR (overall group, left) and leptin (thin subject group including both AN and CT, right).

 
When adjusted for FFM, RMR and TEE values (kJ/kg FFM) were significantly higher in CT than in controls (148.6 ± 5.4 vs. 131.8 ± 10.4, P = 0.009; 259.5 ± 40.6 vs. 208.0 ± 29.5, P = 0.03, respectively) (Table 1).

Similar FQ values were found in all groups. RQ was not found significantly different in CT and controls and was higher in AN.

Among the three groups, free T3, IGF-I, and leptin were significantly lower in AN subjects and showed no significant difference between CT and controls (Table 2).

In observing very thin patients (consisting of both AN and CT subjects), we found a strong correlation between leptin and FM (r = 0.80, P < 0.0001) (Fig. 3) but no correlation between leptin and BMI.


   DISCUSSION
TOP
 ABSTRACT
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
CT is a poorly described entity. This stable, yet severely underweight state, is unexpectedly associated with a biological and hormonal profile similar to that found in normal subjects. In our study, we recruited subjects who were severely thin with BMI <16.5 kg/m2, which is lower than what has been reported in literature (47). In concordance with our previous study (48), we confirmed no difference in free T3, IGF-I, and leptin between the control and CT groups. Low free T3 is a well-known characteristic of undernourished patients, including AN (9, 14). Because free T3 displayed normal levels in CT, as well as IGF-I, another well-known marker of caloric and protein intake (21), we can deduce that caloric and protein intake in the CT group is normal. Furthermore, the psychological profile of CT subjects lacked features commonly observed in AN, which confirms results from previous studies (46). AN features include dieting and binge eating, lower self-esteem, perfectionism, and body dissatisfaction. Among severely underweight subjects (including AN and CT subjects), a strong correlation between leptin and FM measured by DEXA was found. In AN patients, serum leptin is extremely low (<3 ng/ml), whereas in CT subjects, leptin levels were in the normal range (8–12 ng/ml). Similarly, FM is diminished in AN subjects but in CT subjects is present with normal percentages. Therefore, very thin patients with nearly normal levels of leptin and FM should not be confused and diagnosed as AN. This evidence proposes leptin alongside other clinical features in differentiating CT from AN.

To date, no studies have been published on the complete evaluation of energy metabolism observed in CT. Two major aspects of this entity, the steadiness and the etiology of their very low body weight, remain unexplained. To observe whether a possible relationship exists with these aspects, we compared CT energetic profile with those of AN and controls.

First, we found a negative energy balance in restrictive AN. To our knowledge, this is the first study to perform a complete evaluation of energy metabolism (considering both energy intake and energy expenditure) in AN. Although food intake evaluation is questionable in AN, our AN subjects displayed severe-to-very severe reduction of caloric intake (around 4,500 kJ/day), similar to results found in previous studies (18, 20). AN energy expenditure profiles including TEE (8,001 ± 2,152 kJ/day) and RMR (3,810 ± 937 kJ/day) were also found to be similar to those in other studies (35, 52). These collaborated data lead us to say that negative balance of AN is not questionable. The real question is the discrepancy between this negative energy balance and the apparent steady weight in AN (weight loss slows when very low values of BMI are reached). However, the study design was not focused on this pathology and thus did not allow for the clarification of this problem.

Next, in our study, self-reported caloric intake of CT subjects was not found significantly different from that of controls but was higher than in AN. Moreover, the percentages of each nutrient consumed in CT subjects were also found to be similar to those of controls. As already mentioned above, AN subjects displayed a lower caloric and lipid intake and a higher percentage of protein intake (18, 19). Using DLW assessment, we observed that TEE in the CT group was not significantly different from that of controls and AN. In the CT group, the difference between the energy expenditure and the energy intake (816 kJ/day) was similar to that of controls (832 kJ/day), values that, according to literature, are insignificant (42). This demonstrates for the first time that energy metabolism profile explains the steady weight in this phenotype of thinness.

TEE is accounted for by three main components: RMR (resting energy expenditure – ~60% of TEE), physical activity (nonresting energy expenditure – ~30% of TEE), and the thermic effect of feeding (~10% of TEE) (25, 37). RMR was found to be lower in the CT group than in controls but higher than in AN. Similar results have been found in constitutionally lean children (49). Physical activity evaluated by MOSPA-Q displayed no difference between CT and controls. Because TEE found in CT was equivalent to that of controls, composed of similar physical activity but lower RMRs, we deduced an increase in nonexercise activity thermogenesis in CT that could explain their resistance to weight gain (27).

RMR is essentially connected to active cellular mass mainly represented by muscles and compartments of FFM (8, 50). When adjustments for the differences in metabolic mass were made, RMR and TEE values were found significantly higher in CT than in controls. This relative increase in energy expenditure could also account for the "inability" of CT subjects to gain weight when desired. Interestingly, a similar lean phenotype was described in RIIbeta knockout mice including normal food intake, increased metabolic rate and body temperature, and resistance to diet-induced obesity (11).

Because a stable weight in CT denotes equilibrium in energy metabolism, the etiology of this phenotype remains to be explored. Candidate genes, controlling body composition and resistance to the development of obesity (7), should be considered in further research. Two major traits sustaining this hypothesis, the consistency of a low BMI throughout life and its familiality, were confirmed in our study.


   GRANTS
TOP
 ABSTRACT
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
REFERENCES
 
This work was supported by a grant from the Direction Régionale de la Recherche Clinique Saint Etienne, France.


   ACKNOWLEDGMENTS
 
We thank Ms. Jochebed Jolie Pun from the Micheal G. DeGroote School of Medicine, Hamilton, ON, Canada, for correcting the English of this paper.


   FOOTNOTES
 

Address for reprint requests and other correspondence: B. Estour, Service d'endocrinologie diabète et maladies métaboliques, Hôpital Bellevue, CHU Saint Etienne, 42055 Saint Etienne Cedex 02, France (e-mail address: bruno.estour{at}chu-st-etienne.fr)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 

  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Washington, DC: American Psychiatric Association, 1994.
  2. Apfelbaum M, Sachet P. [Constitutional thinness]. Rev Prat 32: 245–247, 1982.[ISI][Medline]
  3. Bertrais S, Galan P, Renault N, Zarebska M, Preziosi P, Hercberg S. Consumption of soup and nutritional intake in French adults: consequences for nutritional status. J Hum Nutr Diet 14: 121–128, 2001.[CrossRef][ISI][Medline]
  4. Bisacchi U, Comastri G, Morabito F, Rovescalli A. [Aspects of lipid metabolism in constitutional leanness]. Riv Clin Pediatr 78: 515–521, 1966.[Medline]
  5. Black AE, Prentice AM, Coward WA. Use of food quotients to predict respiratory quotients for the doubly-labelled water method of measuring energy expenditure. Hum Nutr Clin Nutr 40: 381–391, 1986.[Medline]
  6. Bonnefoy M, Normand S, Pachiaudi C, Lacour JR, Laville M, Kostka T. Simultaneous validation of ten physical activity questionnaires in older men: a doubly labeled water study. J Am Geriatr Soc 49: 28–35, 2001.[CrossRef][ISI][Medline]
  7. Bulik CM, Allison DB. The genetic epidemiology of thinness. Obes Rev 2: 107–115, 2001.[CrossRef][Medline]
  8. Butte NF, Treuth MS, Mehta NR, Wong WW, Hopkinson JM, Smith EO. Energy requirements of women of reproductive age. Am J Clin Nutr 77: 630–638, 2003.[Abstract/Free Full Text]
  9. Chopra IJ, Smith SR. Circulating thyroid hormones and thyrotropin in adult patients with protein-calorie malnutrition. J Clin Endocrinol Metab 40: 221–227, 1975.[Abstract]
  10. Cooper Z, Fairburn CG. The Eating Disorders Examination: a semistructured interview for the assessment of the specific psychopathology of eating disorders. Int J Eat Disord 6: 1–8, 1987.
  11. Cummings DE, Brandon EP, Planas JV, Motamed K, Idzerda RL, McKnight GS. Genetically lean mice result from targeted disruption of the RII beta subunit of protein kinase A. Nature 382: 622–626, 1996.[CrossRef][Medline]
  12. Deeb SS, Fajas L, Nemoto M, Pihlajamaki J, Mykkanen L, Kuusisto J, Laakso M, Fujimoto W, Auwerx J. A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet 20: 284–287, 1998.[CrossRef][ISI][Medline]
  13. de Rijke CE, Jackson PJ, Garner KM, van Rozen RJ, Douglas NR, Kas MJ, Millhauser GL, Adan RA. Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness. Biochem Pharmacol 70: 308–316, 2005.[CrossRef][ISI][Medline]
  14. de Rosa G, Della Casa S, Corsello SM, Ruffilli MP, de Rosa E, Pasargiklian E. Thyroid function in altered nutritional state. Exp Clin Endocrinol 82: 173–177, 1983.[ISI][Medline]
  15. Ferrannini E. The theoretical bases of indirect calorimetry: a review. Metabolism 37: 287–301, 1988.[CrossRef][ISI][Medline]
  16. Fuller NJ, Jebb SA, Laskey MA, Coward WA, Elia M. Four-component model for the assessment of body composition in humans: comparison with alternative methods, and evaluation of the density and hydration of fat-free mass. Clin Sci (Lond) 82: 687–693, 1992.[Medline]
  17. Garner DM, Olmstead MP, Polivy J. Development and validation of a multidimensional eating disorder inventory for anorexia nervosa and bulimia. Int J Eat Disord 2: 15–34, 1983.
  18. Gwirtsman HE, Kaye WH, Curtis SR, Lyter LM. Energy intake and dietary macronutrient content in women with anorexia nervosa and volunteers. J Am Diet Assoc 89: 54–57, 1989.[ISI][Medline]
  19. Hadigan CM, Anderson EJ, Miller KK, Hubbard JL, Herzog DB, Klibanski A, Grinspoon SK. Assessment of macronutrient and micronutrient intake in women with anorexia nervosa. Int J Eat Disord 28: 284–292, 2000.[CrossRef][ISI][Medline]
  20. Holtkamp K, Hebebrand J, Herpertz-Dahlmann B. The contribution of anxiety and food restriction on physical activity levels in acute anorexia nervosa. Int J Eat Disord 36: 163–171, 2004.[CrossRef][ISI][Medline]
  21. Isley WL, Underwood LE, Clemmons DR. Dietary components that regulate serum somatomedin-C concentrations in humans. J Clin Invest 71: 175–182, 1983.[ISI][Medline]
  22. Jaeger B, Ruggiero GM, Edlund B, Gomez-Perretta C, Lang F, Mohammadkhani P, Sahleen-Veasey C, Schomer H, Lamprecht F. Body dissatisfaction and its interrelations with other risk factors for bulimia nervosa in 12 countries. Psychother Psychosom 71: 54–61, 2002.[CrossRef][ISI][Medline]
  23. Laskarzewski PM, Khoury P, Morrison JA, Kelly K, Mellies MJ, Glueck CJ. Familial obesity and leanness. Int J Obes 7: 505–527, 1983.[ISI][Medline]
  24. Lavebratt C, Wahlqvist S, Nordfors L, Hoffstedt J, Arner P. AHSG gene variant is associated with leanness among Swedish men. Hum Genet 117: 54–60, 2005.[CrossRef][ISI][Medline]
  25. Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med 332: 621–628, 1995.[Abstract/Free Full Text]
  26. Le Moullec N, Deheeger M, Preziosi P, Monteiro P, Valeix P, Rolland-Cachera MF, Potier de Courcy G, Cherouvrier F, Christides JP, Galan P, Hercberg S. Validation du manuel photos utilisé pour l'enquête alimentaire de l'Etude SU.VI.MAX. Cah Nutr Diet 31: 158–164, 1996.
  27. Levine JA, Eberhardt NL, Jensen MD. Role of nonexercise activity thermogenesis in resistance to fat gain in humans. Science 283: 212–214, 1999.[Abstract/Free Full Text]
  28. Magnusson PK, Rasmussen F. Familial resemblance of body mass index and familial risk of high and low body mass index. A study of young men in Sweden. Int J Obes Relat Metab Disord 26: 1225–1231, 2002.[CrossRef][ISI][Medline]
  29. Marks DL, Boucher N, Lanouette CM, Perusse L, Brookhart G, Comuzzie AG, Chagnon YC, Cone RD. Ala67Thr polymorphism in the Agouti-related peptide gene is associated with inherited leanness in humans. Am J Med Genet A 126: 267–271, 2004.[Medline]
  30. Mazess RB, Barden HS, Bisek JP, Hanson J. Dual-energy x-ray absorptiometry for total-body and regional bone-mineral and soft-tissue composition. Am J Clin Nutr 51: 1106–1112, 1990.[Abstract/Free Full Text]
  31. Owen JB. Genetic aspects of body composition. Nutrition 15: 609–613, 1999.[CrossRef][ISI][Medline]
  32. Paggi A, Di Giovanni N, Natoli A. [Study of thyroid function in constitutionally thin subjects]. Boll Soc Ital Biol Sper 51: 1–4, 1975.[ISI][Medline]
  33. Parker E, Phillips DI, Cockington RA, Cull C, Poulton J. A common mitchondrial DNA variant is associated with thinness in mothers and their 20-yr-old offspring. Am J Physiol Endocrinol Metab 289: E1110–E1114, 2005.[Abstract/Free Full Text]
  34. Pereira MA, FitzerGerald SJ, Gregg EW, Joswiak ML, Ryan WJ, Suminski RR, Utter AC, Zmuda JM. A collection of Physical Activity Questionnaires for health-related research. Med Sci Sports Exerc 29: S1–S205, 1997.
  35. Platte P, Pirke KM, Trimborn P, Pietsch K, Krieg JC, Fichter MM. Resting metabolic rate and total energy expenditure in acute and weight recovered patients with anorexia nervosa and in healthy young women. Int J Eat Disord 16: 45–52, 1994.[ISI][Medline]
  36. Ramacciotti CE, Coli E, Biadi O, Dell'Osso L. Silent pericardial effusion in a sample of anorexic patients. Eat Weight Disord 8: 68–71, 2003.
  37. Ravussin E, Bogardus C. Relationship of genetics, age, and physical fitness to daily energy expenditure and fuel utilization. Am J Clin Nutr 49: 968–975, 1989.
  38. Ritz P, Johnson PG, Coward WA. Measurements of 2H and 18O in body water: analytical considerations and physiological implications. Br J Nutr 72: 3–12, 1994.[ISI][Medline]
  39. Roeykens J, Rogers R, Meeusen R, Magnus L, Borms J, de Meirleir K. Validity and reliability in a Flemish population of the WHO-MONICA Optional Study of Physical Activity Questionnaire. Med Sci Sports Exerc 30: 1071–1075, 1998.
  40. Rolland-Cachera MF, Cole TJ, Sempe M, Tichet J, Rossignol C, Charraud A. Body mass index variations: centiles from birth to 87 years. Eur J Clin Nutr 45: 13–21, 1991.[ISI][Medline]
  41. Scalfi L, Coltorti A, Sapio C, Caso G, Contaldo F. [Basal metabolism and postprandial thermogenesis in anorexia nervosa and constitutional leanness]. Minerva Endocrinol 16: 43–46, 1991.[Medline]
  42. Scalfi L, Marra M, Caldara A, Silvestri E, Contaldo F. Changes in bioimpedance analysis after stable refeeding of undernourished anorexic patients. Int J Obes Relat Metab Disord 23: 133–137, 1999.[CrossRef][ISI][Medline]
  43. Schneider L, Heard I, Breart G, Henrion R. [Maternal thinness and pregnancy]. Arch Fr Pediatr 36: 1068–1074, 1979.[ISI][Medline]
  44. Schoeller DA, Ravussin E, Schutz Y, Acheson KJ, Baertschi P, Jequier E. Energy expenditure by doubly labeled water: validation in humans and proposed calculation. Am J Physiol Regul Integr Comp Physiol 250: R823–R830, 1986.[Abstract/Free Full Text]
  45. Seale JL, Conway JM, Canary JJ. Seven-day validation of doubly labeled water method using indirect room calorimetry. J Appl Physiol 74: 402–409, 1993.[Abstract/Free Full Text]
  46. Slof R, Mazzeo S, Bulik CM. Characteristics of women with persistent thinness. Obes Res 11: 971–977, 2003.[ISI][Medline]
  47. Tagami T, Satoh N, Usui T, Yamada K, Shimatsu A, Kuzuya H. Adiponectin in anorexia nervosa and bulimia nervosa. J Clin Endocrinol Metab 89: 1833–1837, 2004.[Abstract/Free Full Text]
  48. Tolle V, Kadem M, Bluet-Pajot MT, Frere D, Foulon C, Bossu C, Dardennes R, Mounier C, Zizzari P, Lang F, Epelbaum J, Estour B. Balance in ghrelin and leptin plasma levels in anorexia nervosa patients and constitutionally thin women. J Clin Endocrinol Metab 88: 109–116, 2003.[Abstract/Free Full Text]
  49. Tounian P, Dumas C, Veinberg F, Girardet JP. Resting energy expenditure and substrate utilisation rate in children with constitutional leanness or obesity. Clin Nutr 22: 353–357, 2003.[CrossRef][ISI][Medline]
  50. Valencia ME, Moya SY, McNeill G, Haggarty P. Basal metabolic rate and body fatness of adult men in northern Mexico. Eur J Clin Nutr 48: 205–211, 1994.[ISI][Medline]
  51. Van Strien T, Friejters JE, Bergers GPA, Defares PB. The Dutch Eating Behavior Questionnaire for assessment of restrained, emotional and external eating behavior. Int J Eat Disord 5: 295–315, 1986.
  52. Winter TA, O'Keefe SJ, Callanan M, Marks T. The effect of severe undernutrition and subsequent refeeding on whole-body metabolism and protein synthesis in human subjects. JPEN J Parenter Enteral Nutr 29: 221–228, 2005.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Am. J. Clin. Nutr.Home page
N. Germain, B. Galusca, C. W Le Roux, C. Bossu, M. A Ghatei, F. Lang, S. R Bloom, and B. Estour
Constitutional thinness and lean anorexia nervosa display opposite concentrations of peptide YY, glucagon-like peptide 1, ghrelin, and leptin
Am. J. Clinical Nutrition, April 1, 2007; 85(4): 967 - 971.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
292/1/E132    most recent
00241.2006v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (3)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bossu, C.
Right arrow Articles by Estour, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bossu, C.
Right arrow Articles by Estour, B.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2007 by the American Physiological Society.