Unlu Yigit, Stinson Emma J, Krakoff Jonathan, Piaggi Paolo
Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Phoenix, AZ, United States of America.
Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Phoenix, AZ, United States of America; Department of Information Engineering, University of Pisa, Pisa, Italy.
Metabolism. 2025 Aug;169:156270. doi: 10.1016/j.metabol.2025.156270. Epub 2025 Apr 21.
Protein oxidation (PROTOX) typically accounts for the smallest fraction of daily energy expenditure (24hEE) in humans compared to carbohydrate and lipid oxidation. However, inter-individual differences in PROTOX may explain differences in fuel partitioning and body weight change. We aimed to elucidate the physiological determinants of PROTOX under controlled 24-h dietary conditions, including eucaloric feeding, fasting, and overfeeding diets with variable protein content.
Eighty-six weight-stable healthy volunteers with normal glucose regulation (67 M/19F; age: 37 ± 10 years; BMI: 26.7 ± 4.5 kg/m, body fat by DXA: 29.0 ± 9.8 %) underwent 24hEE measurements by whole-room calorimetry during energy balance (20 % protein, 50 % carbohydrate), different overfeeding diets (200 % of the daily eucaloric requirement), including three normal-protein (20 %) diets (balanced: 50 % carbohydrate; high-carbohydrate: 75 % carbohydrate; high-fat: 60 % fat), low-protein (3 %) and high-protein (30 %), and 24-h fasting in a randomized crossover design. Urine samples were collected during each 24-h dietary intervention for quantification of PROTOX and catecholamine excretion rates by nitrogen excretion and high-performance liquid chromatography, respectively.
PROTOX during energy balance (mean ± SD: 372 ± 78 kcal/day) was positively associated with protein intake (r = 0.39, p < 0.001), fat free mass (r = 0.35, p < 0.001), but not with fat mass (p = 0.24). Higher PROTOX was associated with higher 24-h urinary norepinephrine (partial r = 0.27, p = 0.01), but not epinephrine (p = 0.48), excretion rates. During normal-protein diets, higher PROTOX was associated with lower lipid oxidation, but showed no association with carbohydrate oxidation. Inter-individual variability in PROTOX did not predict changes in weight or body composition over two years.
Dietary protein content, lean body mass, and sympathetic nervous system activity are key determinants of PROTOX. Although PROTOX did not predict free-living weight gain, increased PROTOX is associated with decreased lipid oxidation, underscoring its role in fuel partitioning and whole-body energy and substrate balance.
与碳水化合物和脂质氧化相比，蛋白质氧化（PROTOX）在人类每日能量消耗（24小时能量消耗，24hEE）中通常占比最小。然而，PROTOX的个体差异可能解释了能量分配和体重变化的差异。我们旨在阐明在24小时可控饮食条件下PROTOX的生理决定因素，包括等热量喂养、禁食以及蛋白质含量可变的过量喂养饮食。
86名体重稳定、葡萄糖调节正常的健康志愿者（67名男性/19名女性；年龄：37±10岁；体重指数：26.7±4.5kg/m²，双能X线吸收法测量体脂：29.0±9.8%）在能量平衡状态（20%蛋白质，50%碳水化合物）、不同的过量喂养饮食（每日等热量需求的200%）期间，通过全室量热法进行24hEE测量，过量喂养饮食包括三种正常蛋白质（20%）饮食（均衡型：50%碳水化合物；高碳水化合物型：75%碳水化合物；高脂肪型：60%脂肪）、低蛋白（3%）和高蛋白（30%）饮食，以及采用随机交叉设计进行24小时禁食。在每次24小时饮食干预期间收集尿液样本，分别通过氮排泄和高效液相色谱法定量PROTOX和儿茶酚胺排泄率。
能量平衡期间的PROTOX（均值±标准差：372±78千卡/天）与蛋白质摄入量呈正相关（r=0.39，p<0.001），与去脂体重呈正相关（r=
