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The circulating metabolome of human starvation
Matthew L. Steinhauser, … , Clary B. Clish, Pouneh K. Fazeli
Matthew L. Steinhauser, … , Clary B. Clish, Pouneh K. Fazeli
Published August 23, 2018
Citation Information: JCI Insight. 2018;3(16):e121434. https://doi.org/10.1172/jci.insight.121434.
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Research Article Endocrinology Metabolism

The circulating metabolome of human starvation

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Abstract

The human adaptive starvation response allows for survival during long-term caloric deprivation. Whether the physiology of starvation is adaptive or maladaptive is context dependent: activation of pathways by caloric restriction may promote longevity, yet in the context of caloric excess, the same pathways may contribute to obesity. Here, we performed plasma metabolite profiling of longitudinally collected samples during a 10-day, 0-calorie fast in humans. We identify classical milestones in adaptive starvation, including the early consumption of gluconeogenic amino acids and the subsequent surge in plasma nonesterified fatty acids that marks the shift from carbohydrate to lipid metabolism, and demonstrate findings, including (a) the preferential release of unsaturated fatty acids and an associated shift in plasma lipid species with high degrees of unsaturation and (b) evidence that acute, starvation-mediated hypoleptinemia may be a driver of the transition from glucose to lipid metabolism in humans.

Authors

Matthew L. Steinhauser, Benjamin A. Olenchock, John O’Keefe, Mingyue Lun, Kerry A. Pierce, Hang Lee, Lorena Pantano, Anne Klibanski, Gerald I. Shulman, Clary B. Clish, Pouneh K. Fazeli

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Figure 1

Starvation results in global shifts in circulating metabolites.

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Starvation results in global shifts in circulating metabolites.
(A) Sche...
(A) Schematic time line of the human-fasting protocol (day 0, baseline day; day 10, final fast day). (B) Heatmap displaying plasma metabolites with fasting (n = 544). RF, refed day 1. (C) The number of metabolites deviating from baseline (day 0) at each time point (adjusted P < 0.05). Blue bars, subset that also deviated by log fold change >0.5. (D) Pie chart showing class breakdown of metabolites represented by blue bars in C. (E) Principal component analysis (PCA) plot of leading principal components (PC1 and PC2). Dark red dots, baseline; dark blue dots, day 10 of fast; lighter shades, intermediate time points. With fasting, subjects converged to the lower right quadrant (dark blue dots).

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