Human metabolic chambers reveal a coordinated metabolic-physiologic response to nutrition

Andrew S. Perry, Paolo Piaggi, Shi Huang, Matthew Nayor, Jane Freedman, Kari North, Jennifer Below, Clary Clish, Venkatesh L. Murthy, Jonathan Krakoff, Ravi V. Shah
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Abstract

The emerging field of precision nutrition is based on the notion that inter-individual responses across diets of different calorie-macronutrient content may contribute to inter-individual differences in metabolism, adiposity, and weight gain. Free-living diet studies have been traditionally challenged by difficulties in controlling adherence to prescribed calories and macronutrient content and rarely allow a period of metabolic stability prior to metabolic measures (to minimize influences of weight changes). In this context, key physiologic measures central to precision nutrition responses may be most precisely quantified via whole room indirect calorimetry over 24-h, in which precise control of activity and nutrition can be achieved. In addition, these studies represent unique “N of 1” human crossover metabolic-physiologic experiments during which specific molecular pathways central to nutrient metabolism may be discerned. Here, we quantified 263 circulating metabolites during a ≈40-day inpatient admission in which up to 94 participants underwent seven monitored 24-h nutritional interventions of differing macronutrient composition in a whole-room indirect calorimeter to capture precision metabolic responses. Broadly, we observed heterogenous responses in metabolites across dietary chambers, with the exception of carnitines which tracked with 24-h respiratory quotient. We identified excursions in shared metabolic species (e.g., carnitines, glycerophospholipids, amino acids) that mapped onto gold-standard calorimetric measures of substrate oxidation preference and lipid availability. These findings support a coordinated metabolic-physiologic response to nutrition, highlighting the relevance of these controlled settings to uncover biological pathways of energy utilization during precision nutrition studies.
人体代谢室揭示了代谢生理对营养的协调反应
新兴的精准营养学领域基于这样一种理念,即不同热量-宏量营养素含量饮食的个体间反应可能导致代谢、脂肪和体重增加的个体间差异。自由生活饮食研究历来受到难以控制遵守规定热量和宏量营养素含量的挑战,而且很少允许在代谢测量前有一段代谢稳定期(以尽量减少体重变化的影响)。在这种情况下,对精确营养反应至关重要的关键生理指标可通过 24 小时全室间接热量测定法进行最精确的量化,从而实现对活动和营养的精确控制。此外,这些研究还代表了独特的 "N of 1 "人体交叉代谢生理实验,在实验过程中可以发现营养代谢的核心分子通路。在这里,我们对住院病人在≈40 天的住院期间的 263 种循环代谢物进行了定量分析,其中有多达 94 名参与者在全室间接热量计中接受了 7 次不同宏量营养素组成的 24 小时监测营养干预,以捕捉精确的代谢反应。大体上,我们观察到不同饮食室中代谢物的异质性反应,但肉碱除外,它与 24 小时呼吸商相关。我们确定了共同代谢物种(如肉毒碱、甘油磷脂、氨基酸)的偏移,这些偏移映射到底物氧化偏好和脂质可用性的黄金标准热量测量上。这些发现支持代谢生理对营养的协调反应,突出了这些受控环境对在精准营养研究中发现能量利用的生物途径的意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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