Division of Endocrinology, CHU Saint-Etienne, Saint-Etienne, France.
Eating Disorders, Addictions & Extreme Bodyweight Research Group, Jean Monnet University, Saint-Etienne, France.
J Cachexia Sarcopenia Muscle. 2020 Oct;11(5):1187-1199. doi: 10.1002/jcsm.12572. Epub 2020 Apr 10.
Constitutional 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.
A 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.
Before 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.
The 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.
体质消瘦（CT）是一种非营养不良性消瘦状态，无饮食失调，其特征是对高脂肪饮食的增重抵抗。肌肉活检数据表明，在自由生活状态下，合成代谢机制减弱。CT 患者对蛋白质热量补充的体重和代谢反应尚未得到探索。
进行为期 2 周的过度喂养（额外 600 千卡，30 克蛋白质，72 克碳水化合物和 21 克脂肪），以比较两组 CT（12 名女性和 11 名男性）与正常体重对照组（12 名女性和 10 名男性）。在过度喂养前后监测体重、食物摄入量、能量消耗、身体成分、氮平衡、食欲激素谱和尿液代谢组。
在过度喂养前，两性 CT 均存在正能量缺口（CT-F 为 309±370 千卡，CT-M 为 332±709 千卡），相对蛋白质摄入量更高/公斤（CT-F 为 1.74±0.32 克/公斤/天，CT-F 为 1.16±0.23 克/公斤/天，P<0.0001；CT-M 为 1.56±0.36 克/公斤/天，CT-M 为 1.22±0.32 克/公斤/天，P=0.03），氮排泄量较低（CT-F 为 7.26±2.36 克/天，CT-F 为 11.41±3.64 克/天，P=0.003；CT-M 为 9.70±3.85 克/天，CT-M 为 14.14±4.19 克/天，P=0.02），但在自由生活条件下，必需氨基酸尿排泄量更高（亮氨酸和精氨酸的 CT/C 比值分别为 1.13 和 1.14）。过度喂养后，CT 仍存在明显的正能量缺口，仍高于对照组（CT 为 675±540 千卡，对照组为 379±427 千卡，P=0.04）。两组对照的瘦体重均增加，但 CT 无增加（CT 女性中出现趋势），尽管过度喂养后氮平衡相似（CT 为 5.06±4.33 克/天，对照组为 4.28±3.15 克/天，P=0.49）。在 CT 中，观察到进食和零食频率较高时，厌食性肠道激素的张力、胰高血糖素样肽 1 和肽酪氨酸酪氨酸增加。
先前在 CT 自由生活状态下描述的肌肉能量机制减弱，与正氮平衡和几种必需氨基酸尿排泄增加所提示的基础饱和蛋白质周转有关。这一饱和状态不能通过增加这种自发的高蛋白摄入来克服，这表明 CT 表型对瘦体重增加存在抵抗。
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