Translational Research Institute, AdventHealth, Orlando, FL, USA.
Cardiovascular Institute and Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Am J Clin Nutr. 2021 Jul 1;114(1):267-280. doi: 10.1093/ajcn/nqab027.
Low-calorie diet (LCD)-induced weight loss demonstrates response heterogeneity. Physiologically, a decrease in energy expenditure lower than what is predicted based on body composition (metabolic adaptation) and/or an impaired capacity to increase fat oxidation may hinder weight loss. Understanding the metabolic components that characterize weight loss success is important for optimizing weight loss strategies.
We tested the hypothesis that overweight/obese individuals who had lower than expected weight loss in response to a 28-d LCD would be characterized by 1) impaired fat oxidation and 2) whole-body metabolic adaptation. We also characterized the molecular mechanisms associated with weight loss success/failure.
This was a retrospective comparison of participants who met their predicted weight loss targets [overweight/obese diet sensitive (ODS), n = 23, females = 21, males = 2] and those that did not [overweight/obese diet resistant (ODR), n = 14, females = 12, males = 2] after a 28-d LCD (900-1000 kcal/d). We used whole-body (energy expenditure and fat oxidation) and tissue-specific measurements (metabolic proteins in skeletal muscle, gene expression in adipose tissue, and metabolites in serum) to detect metabolic properties and biomarkers associated with weight loss success.
The ODR group had greater mean ± SD metabolic adaptation (-175 ± 149 kcal/d; +119%) than the ODS group (-80 ± 108 kcal/d) after the LCD (P = 0.030). Mean ± SD fat oxidation increased similarly for both groups from baseline (0.0701 ± 0.0206 g/min) to day 28 (0.0869 ± 0.0269 g/min; P < 0.001). A principal component analysis factor comprised of serum 3-hydroxybutyric acid, citrate, leucine/isoleucine, acetyl-carnitine, and 3-hydroxylbutyrlcarnitine was associated with weight loss success at day 28 (std. β = 0.674, R2 = 0.479, P < 0.001).
Individuals who achieved predicted weight loss targets after a 28-d LCD were characterized by reduced metabolic adaptation. Accumulation of metabolites associated with acetyl-CoA excess and enhanced ketogenesis was identified in the ODS group.This trial was registered at clinicaltrials.gov as NCT01616082.
低热量饮食（LCD）引起的体重减轻表现出反应异质性。从生理学上讲，能量消耗的减少低于基于身体成分预测的水平（代谢适应）和/或脂肪氧化能力受损，可能会阻碍体重减轻。了解体重减轻成功的代谢成分对于优化体重减轻策略很重要。
我们检验了以下假设，即对 28 天 LCD 反应不佳的超重/肥胖个体的特征为 1）脂肪氧化受损和 2）全身代谢适应。我们还描述了与体重减轻成功/失败相关的分子机制。
这是对满足预测体重减轻目标的参与者[超重/肥胖饮食敏感（ODS），n=23，女性=21，男性=2]和未达到体重减轻目标的参与者[超重/肥胖饮食抵抗（ODR），n=14，女性=12，男性=2]的回顾性比较，他们在 28 天 LCD（900-1000kcal/d）后达到了目标体重。我们使用全身（能量消耗和脂肪氧化）和组织特异性测量（骨骼肌中的代谢蛋白、脂肪组织中的基因表达和血清中的代谢物）来检测与体重减轻成功相关的代谢特性和生物标志物。
LCD 后，ODR 组的平均代谢适应率（-175±149kcal/d；+119%）明显高于 ODS 组（-80±108kcal/d；P=0.030）。两组的平均脂肪氧化率均从基线（0.0701±0.0206g/min）增加到第 28 天（0.0869±0.0269g/min；P<0.001）。由血清 3-羟基丁酸、柠檬酸、亮氨酸/异亮氨酸、乙酰肉碱和 3-羟丁酸肉碱组成的主成分分析因子与第 28 天的体重减轻成功相关（标准β=0.674，R2=0.479，P<0.001）。
在 28 天 LCD 后达到预测体重减轻目标的个体的特征是代谢适应减少。在 ODS 组中发现了与乙酰辅酶 A 过多和增强酮生成相关的代谢物的积累。本试验在 clinicaltrials.gov 注册为 NCT01616082。
