A Metabolomic Signature of Acute Caloric Restriction

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.

Caloric restriction alters lipid metabolism to contribute to tumor growth inhibition

“…Most fatty acids measured are increased by the KD relative to the control diet, consistent with the KD consisting of 90% fat (Extended Data Table 1). In contrast, levels of almost all fatty acids are reduced by CR, particularly in the TIF, which is consistent with previous studies showing how CR can decrease circulating lipid levels [29][30][31][32][33] . This observation suggests that compared to the KD, decreased systemic availability of lipids and fatty acids to the tumor is specific to CR, and environmental lipid limitation could be one metabolic mechanism by which CR inhibits tumor growth.…”

An Integrated Understanding of the Molecular Mechanisms of How Adipose Tissue Metabolism Affects Long-term Body Weight Maintenance

“…Actually, increased levels of short-, medium-, and longchain ACs were repeatedly reported as estimates of impaired b-oxidation in type 2 diabetes (18,(26)(27)(28). But this may also represent a state of energy deficiency, as caloric restriction is known to be associated with increased lipolysis and lipid oxidation, indicated by increase of FFAs and glycerol as well as an elevation of ACs and ketone bodies (29). Thus, lower RQ after weight loss, seen in WM subjects, and the negative association of RQ with almost all ACs during and after weight loss may suggest a stronger switch to lipid oxidation than impaired b-oxidation.…”

Respiratory viral infection alters the gut microbiota by inducing inappetence

“…We hypothesized that reduced food intake during infection would decrease overall nutritional availability within the gut, impacting host and microbiota metabolism and metabolite levels. The faecal metabolome has been shown to be altered by both acute and long-term fasting (Rubio-Aliaga et al, 2011;Zheng et al, 2016;Collet et al, 2017). This is likely to be a combination of direct effects of fasting on host metabolism and indirect effects of altered gut microbiota composition and metabolism.…”