Specific appetite, energetic and metabolomics responses to fat overfeeding in resistant-to-bodyweight-gain constitutional thinness

Supplementary information available for this article at http://www.nature.com/nutd/journal/v4/n7/suppinfo/nutd201417s1.htmlBACKGROUND: 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.OBJECTIVE: The objective of this study was to evaluate appetite regulatory hormones in CTs in an inverse paradigm of diet-induced weight loss.METHODS: 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 k gm(-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.RESULTS: 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).CONCLUSION: 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