An Integrated Understanding of the Molecular Mechanisms of How Adipose Tissue Metabolism Affects Long-term Body Weight Maintenance
An Integrated Understanding of the Molecular Mechanisms of How Adipose Tissue Metabolism Affects Long-term Body Weight Maintenance
复制标题
对脂肪组织代谢如何影响长期体重维持的分子机制的综合理解
DOI：
10.2337/db18-0440
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发表时间：
2019-01-01
期刊：
影响因子：
7.7
通讯作者：
Spranger, Joachim
中科院分区：
文献类型：
--
作者：
Mai, Knut;Li, Linna;Spranger, Joachim
基于生活方式的减肥干预措施经常表现出长期无效和体重反弹。迫切需要确定潜在的机制和预测因素，以确定谁将受益于基于生活方式的减肥策略的主题。我们分析了143名随机维持试验（维持成人）的成年人在预期体重减轻后，以确定有助于调节体重维持的机制。脂肪和骨骼肌活检的无偏RNA测序显示，脂肪酸代谢是体重减轻改变的关键途径。该途径关键酶的变异性、底物氧化的估计值和特定血清酰基肉毒碱（AC）种类（代表体内底物通量的全身快照）预测了整个队列预期体重减轻后18个月的体重维持（定义为连续或二分[< or >= 3%体重恢复]变量）。关键结果在137名儿童和青少年（维持儿童）的类似随机对照试验中得到证实，该试验在儿科队列中研究了相同的范例。这些数据表明，适应脂质利用，以应对负能量平衡有助于随后的体重维持。特别是循环AC的功能作用，这已被建议反映细胞内底物利用，作为外周能量储存和长期能量稳态控制之间的介质被指示。
Lifestyle-based weight loss interventions frequently demonstrate long-term inefficiency and weight regain. Identification of underlying mechanisms and predictors to identify subjects who will benefit from lifestyle-based weight loss strategies is urgently required. We analyzed 143 adults of the randomized Maintain trial (Maintain-Adults) after intended weight loss to identify mechanisms contributing to the regulation of body weight maintenance. Unbiased RNA sequencing of adipose and skeletal muscle biopsies revealed fatty acid metabolism as a key pathway modified by weight loss. Variability of key enzymes of this pathway, estimates of substrate oxidation, and specific serum acylcarnitine (AC) species, representing a systemic snapshot of in vivo substrate flux, predicted body weight maintenance (defined as continuous or dichotomized [< or >= 3% weight regain] variable) 18 months after intended weight loss in the entire cohort. Key results were confirmed in a similar randomized controlled trial in 137 children and adolescents (Maintain-Children), which investigated the same paradigm in a pediatric cohort. These data suggest that adaption of lipid utilization in response to negative energy balance contributes to subsequent weight maintenance. Particularly a functional role for circulating ACs, which have been suggested to reflect intracellular substrate utilization, as mediators between peripheral energy stores and control of long-term energy homeostasis was indicated.