Abstract
Context:The experimental paradigm of acute caloric restriction (CR) followed by refeeding (RF) can be used to study the homeostatic mechanisms that regulate energy homeostasis, which are relevant to understanding the adaptive response to weight loss.Objective:Metabolomics, the measurement of hundreds of small molecule metabolites, their precursors, derivatives, and degradation products, has emerged as a useful tool for the study of physiology and disease and was used here to study the metabolic response to acute CR.Participants, Design, and Setting:We used four ultra high-performance liquid chromatography-tandem mass spectrometry methods to characterize changes in carbohydrates, lipids, amino acids, and steroids in eight normal weight men at baseline, after 48 hours of CR (10% of energy requirements) and after 48 hours of ad libitum RF in a tightly controlled environment.Results:We identified a distinct metabolomic signature associated with acute CR characterized by the expected switch from carbohydrate to fat utilization with increased lipolysis and β-fatty acid oxidation. We found an increase in ω-fatty acid oxidation and levels of endocannabinoids, which are known to promote food intake. These changes were reversed with RF. Several plasmalogen phosphatidylethanolamines (endogenous antioxidants) significantly decreased with CR (all P ≤ 0.0007). Additionally, acute CR was associated with an increase in the branched chain amino acids (all P ≤ 1.4 × 10−7) and dehydroepiandrosterone sulfate (P = 0.0006).Conclusions:We identified a distinct metabolomic signature associated with acute CR. Further studies are needed to characterize the mechanisms that mediate these changes and their potential contribution to the adaptive response to dietary restriction.
Highlights
We identified a distinct metabolomic signature associated with acute caloric restriction (CR) characterized by the expected switch from carbohydrate to fat utilization with increased lipolysis and b-fatty acid oxidation
First Published Online 28 September 2017 fat mass leads to a fall in circulating leptin concentrations triggering changes in energy intake, energy expenditure, and neuroendocrine function that restore energy homeostasis, resulting in rebound weight gain—the phenomenon popularly known as yo-yo dieting
We explored the metabolomic profile for each participant at baseline, CR, and in the refed state by employing multivariate statistical analyses to analyze state-dependent changes
Summary
Experimental design of study The study was approved by the Cambridge local research ethics committee and was conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent was received from each participant prior to inclusion in the study. We recruited eight normal weight healthy men using the following inclusion criteria: normal glucose tolerance measured by a 75-g oral glucose tolerance test, no evidence of renal, liver, or thyroid disease, average alcohol intake ,2 units/d, not participating in an organized exercise program, not treated with anorectic agents or medications known to affect carbohydrate and/or lipid metabolism, or blood pressure. Shift workers were excluded from the study; all participants had a normal sleep/wake pattern as determined by polysomnography at screening. Weight and height were measured barefoot in light clothing and body mass index calculated (weight in kg/height in meters squared).
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