Metabolomics identifies increases in the acylcarnitine profiles in the plasma of overweight subjects in response to mild weight loss: a randomized, controlled design study

Abstract

Background: Using metabolomics technique to analyze the response to a dietary intervention generates valuable information concerning the effects of the prescribed diet on metabolic regulation. To determine whether low calorie diet (LCD)-induced weight reduction causes changes in plasma metabolites and metabolic characteristics.

Methods: Overweight subjects consumed a LCD (n = 47) or a weight maintenance diet (control, n = 50) in a randomized, controlled design study with a 12-week clinical intervention period. Plasma samples were analyzed using an UPLC-LTQ-Orbitrap MS.

Results: The 12-week LCD intervention resulted in significant mild weight loss, with an 8.3% and 10.6% reduction observed in the visceral fat area (VFA) at the level of the lumbar vertebrae L1 and L4, respectively. The LCD group showed a significant increase in the mean change of serum free fatty acids compared to the control group. In the LCD group, we observed a significant increase in the acylcarnitine (AC) levels, including hexanoylcarnitine, L-octanoylcarnitine, 9-decenoylcarnitine, trans-2-dodecenoylcanitine, dodecanoylcarnitine, 3,5-tetradecadiencarnitine, cis-5-tetradecenoylcarnitine, 9,12-hexadecadienoylcarnitine, and 9-hexadecenoylcarnitne at the 12-week follow-up assessment. When the plasma metabolite changes from baseline were compared between the control and LCD groups, the LCD group showed significant increases in hexanoylcarnitine, L-octanoylcarnitine, trans-2-dodecenoylcanitine, and 3,5-tetradecadiencarnitine than the control group. Additionally, the changes in these ACs in the LCD group strongly negatively correlated with the changes in the VFA at L1 and/or L4.

Conclusion: Mild weight loss from 12-week calorie restriction increased the plasma levels of medium- and long-chain ACs. These changes were coupled with a decrease in VFA and an increase in free fatty acids.

Trial registration: NCT03135132 ; April 26, 2017.

Keywords: Acylcarnitine; Low calorie diet; Metabolomics; Mild weight loss; Visceral fat area.

Conflict of interest statement

Ethics approval and consent to participate

We gave all subjects a careful explanation of the purpose of the study and received written consent prior to their participation. The protocol used in the study was approved by the the Institutional Review Boards of Yonsei University and the Yonsei University Severance Hospital approved the study protocol, which complied with the Declaration of Helsinki.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

Identification of plasma metabolites with significantly altered levels. a Score plots from the OPLS-DA models in the control group (n = 50); comparison between baseline (yellow) and follow-up (blue). b Score plots from the OPLS-DA models in the low calorie diet (LCD) group (n = 47); comparison between baseline (green) and follow-up (red). c Score plots from the OPLS-DA models at follow-up; comparison between follow-up in the control (n = 50, blue) and LCD (n = 47, red) groups

Fig. 2

Correlation matrix among the changes (Δ) from baseline in clinical parameters and major metabolites in the control and low calorie diet (LCD) groups. Correlations were obtained by deriving a Pearson correlation coefficient. Red indicates a positive correlation, and blue indicates a negative correlation

Fig. 3

Correlation scatter plots of changes (Δ) from baseline in the major acylcarnitines and visceral fat areas at L1 and L4 in the low calorie diet (LCD) group. a, b, c, d Correlations between Δ hexanoylcarnitine, Δ L-octanoylcarnitine, Δ trans-2-dodecenoylcarnitine, Δ 3,5-tetradecadiencarnitine and Δ visceral fat area at L1, respectively. e, f, g, h Correlations between Δ hexanoylcarnitine, Δ L-octanoylcarnitine, Δ trans-2-dodecenoylcarnitine, Δ 3,5-tetradecadiencarnitine and Δ visceral fat area at L4, respectively