New Insights on Bone Tissue and Structural Muscle-Bone Unit in Constitutional Thinness.
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ABSTRACT:
SUBMITTER: Bailly M
PROVIDER: S-EPMC9305386 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeStudying the plasma proteome of control versus constitutionally thin (CT) individuals, exposed to overfeeding, may give insights into weight-gain management, providing relevant information to the clinical entity of weight-gain resistant CT, and discovering new markers for the condition.Experimental designUntargeted protein relative quantification of 63 CT and normal-weight individuals was obtained in blood plasma at baseline, during and after an overfeeding challenge using mass spectrometry-based proteomics.ResultsThe plasma proteome of CT subjects presented limited specificity with respect to controls at baseline. Yet, CT showed lower levels of inflammatory C-reactive protein and larger levels of protective insulin-like growth factor-binding protein 2. Differences were more marked during and after overfeeding. CT plasma proteome showed larger magnitude and significance in response, suggesting enhanced "resilience" and more rapid adaptation to changes. Four proteins behaved similarly between CT and controls, while five were regulated in opposite fashion. Ten proteins were differential during overfeeding in CT only (including increased fatty acid-binding protein and glyceraldehyde-3-phosphate dehydrogenase, and decreased apolipoprotein C-II and transferrin receptor protein 1).Conclusions and clinical relevanceThis first proteomic profiling of a CT cohort reveals different plasma proteomes between CT subjects and controls in a longitudinal clinical trial. Our molecular observations further support that the resistance to weight gain in CT subjects appears predominantly biological.Clinicaltrialsgov Identifier: NCT02004821.
| S-EPMC9787820 | biostudies-literature
Project description:INTRODUCTION:Interleukin-7 (IL-7) is a cytokine involved in energy homeostasis as demonstrated in rodents. Anorexia nervosa is characterized by restrained eating behavior despite adaptive orexigenic regulation profile including high ghrelin plasma levels. Constitutional thinness is a physiological condition of resistance to weight gain with physiological anorexigenic profile including high Peptide YY plasma level. Healthy obesity can be considered as a physiological state of resistance to weight loss with opposite appetite regulating profile to constitutional thinness including low Peptide YY plasma level. No studies in IL-7 are yet available in those populations. Therefore we evaluated circadian plasma levels of IL-7 in anorexia nervosa compared to constitutional thinness, healthy obese and control females. MATERIALS AND METHODS:10 restrictive-type anorexia nervosa women, 5 bingeing/purging anorexia nervosa woman, 5 recovered restrictive anorexia nervosa women, 4 bulimic females, 10 constitutional thinness women, 7 healthy obese females, and 10 normal weight women controls were enrolled in this cross-sectional study, performed in endocrinology unit and academic laboratory. Twelve-point circadian profiles of plasma IL-7 levels were measured in each subject. RESULTS:24h mean IL-7 plasma levels (pg/ml, mean±SEM) were decreased in restrictive-type anorexia nervosa (123.4±14.4, p<0.0037), bingeing/purging anorexia nervosa (24.2±5.6, p<0.001), recovered restrictive anorexia nervosa (64.2±16.1, p = 0.01) and healthy obese patients (51±3.2, p<0.001) compared to controls (187.7±28.6). Bulimic patients (197.4±42.7) and constitutional thinness patients (264.3±35.8) were similar to controls. CONCLUSIONS:Low IL-7 is part of the adaptive profile in restrictive-type anorexia nervosa, confirming its difference with constitutional thinness. Healthy obesity, with low IL-7, is once again in mirror image of constitutional thinness with normal high IL-7.
| S-EPMC5017702 | biostudies-literature
Project description:Contrasting with obesity, constitutional thinness (CT) is a rare condition of natural low bodyweight. CT exhibits preserved menstruation in females, no biological marker of undernutrition, no eating disorders but a bodyweight gain desire. Anorexigenic hormonal profile with high peptide tyrosine tyrosine (PYY) was shown in circadian profile. CT could be considered as the opposite of obesity, where some patients appear to resist diet-induced bodyweight loss.The objective of this study was to evaluate appetite regulatory hormones in CTs in an inverse paradigm of diet-induced weight loss.A 4-week fat overfeeding (2640?kJ excess) was performed to compare eight CT women (body mass index (BMI)<17.5?kg?m(-)(2)) to eight female controls (BMI 18.5-25?kg?m(-)(2)). Appetite regulatory hormones profile after test meal, food intake, bodyweight, body composition, energy expenditure and urine metabolomics profiles were monitored before and after overfeeding.After overfeeding, fasting total and acylated ghrelin were significantly lower in CTs than in controls (P=0.01 and 0.03, respectively). After overfeeding, peptide tyrosine tyrosine (PYY) and glucagon-like-peptide 1 both presented earlier (T15 min vs T30 min) and higher post-meal responses (incremental area under the curve) in CTs compared with controls. CTs failed to increase bodyweight (+0.22±0.18?kg, P=0.26 vs baseline), contrasting with controls (+0.72±0.26?kg, P=0.03 vs baseline, P=0.01 vs CTs). Resting energy expenditure increased in CTs only (P=0.031 vs baseline). After overfeeding, a significant negative difference between total energy expenditure and food intake was noticed in CTs only (-2754±720?kJ, P=0.01).CTs showed specific adaptation to fat overfeeding: overall increase in anorexigenic hormonal profile, enhanced post prandial GLP-1 and PYY and inverse to controls changes in urine metabolomics. Overfeeding revealed a paradoxical positive energy balance contemporary to a lack of bodyweight gain, suggesting yet unknown specific energy expenditure pathways in CTs.
| S-EPMC5189928 | biostudies-literature
Project description:BackgroundConstitutional thinness (CT), a non-malnourished underweight state with no eating disorders, is characterized by weight gain resistance to high fat diet. Data issued from muscle biopsies suggested blunted anabolic mechanisms in free-living state. Weight and metabolic responses to protein caloric supplementation has not been yet explored in CT.MethodsA 2 week overfeeding (additional 600 kcal, 30 g protein, 72 g carbohydrate, and 21 g fat) was performed to compare two groups of CTs (12 women and 11 men) to normal-weight controls (12 women and 10 men). Bodyweight, food intake, energy expenditure, body composition, nitrogen balance, appetite hormones profiles, and urine metabolome were monitored before and after overfeeding.ResultsBefore overfeeding, positive energy gap was found in both CT genders (309 ± 370 kcal in CT-F and 332 ± 709 kcal in CT-M) associated with higher relative protein intake per kilo (1.74 ± 0.32 g/kg/day in CT-F vs. 1.16 ± 0.23 in C-F, P < 0.0001; 1.56 ± 0.36 in CT-M vs. 1.22 ± 0.32 in C-M, P = 0.03), lower nitrogen (7.26 ± 2.36 g/day in CT-F vs. 11.41 ± 3.64 in C-F, P = 0.003; 9.70 ± 3.85 in CT-M vs. 14.14 ± 4.19 in C-M, P = 0.02), but higher essential amino acids urinary excretion (CT/C fold change of 1.13 for leucine and 1.14 for arginine) in free-living conditions. After overfeeding, CTs presented an accentuated positive energy gap, still higher than in controls (675 ± 540 in CTs vs. 379 ± 427 in C, P = 0.04). Increase in lean mass was induced in both controls genders but not in CTs (a trend was noticed in CT women), despite a similar nitrogen balance after overfeeding (5.06 ± 4.33 g/day in CTs vs. 4.28 ± 3.15 in controls, P = 0.49). Higher anorectic gut hormones' tone, glucagon-like peptide 1 and peptide tyrosine tyrosine, during test meal and higher snacking frequency were noticed before and after overfeeding in CTs.ConclusionsThe blunted muscle energy mechanism, previously described in CTs in free-living state, is associated with basal saturated protein turn over suggested by the concordance of positive nitrogen balance and an increased urine excretion of several essential amino acids. This saturation cannot be overpassed by increasing this spontaneous high-protein intake suggesting a resistance to lean mass gain in CT phenotype.
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